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  1. Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA.

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    Jana Ferdin

    Full Text Available To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort. We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

  2. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

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    Ricard Dominique

    2010-05-01

    Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

  3. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

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    Baroncelli, Silvia; Pirillo, Maria F; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-07-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

  4. Meticulous plasma isolation is essential to avoid false low-level viraemia in Roche Cobas HIV-1 viral load assays.

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    Mortier, Virginie; Vancoillie, Leen; Dauwe, Kenny; Staelens, Delfien; Demecheleer, Els; Schauvliege, Marlies; Dinakis, Sylvie; Van Maerken, Tom; Dessilly, Géraldine; Ruelle, Jean; Verhofstede, Chris

    2017-10-24

    Pre-analytical sample processing is often overlooked as a potential cause of inaccurate assay results. Here we demonstrate how plasma, extracted from standard EDTA-containing blood collection tubes, may contain traces of blood cells consequently resulting in a false low-level HIV-1 viral load when using Roche Cobas HIV-1 assays. The presence of human DNA in Roche Cobas 4800 RNA extracts and in RNA extracts from the Abbott HIV-1 RealTime assay was assessed by quantifying the human albumin gene by means of quantitative PCR. RNA was extracted from plasma samples before and after an additional centrifugation and tested for viral load and DNA contamination. The relation between total DNA content and viral load was defined. Elevated concentrations of genomic DNA were detected in 28 out of 100 Cobas 4800 extracts and were significantly more frequent in samples processed outside of the AIDS Reference Laboratory. An association between genomic DNA presence and spurious low-level viraemia results was demonstrated. Supplementary centrifugation of plasma before RNA extraction eliminated the contamination and the false viraemia. Plasma isolated from standard EDTA-containing blood collection tubes may contain traces of HIV DNA leading to false viral load results above the clinical cutoff. Supplementary centrifugation of plasma before viral load analysis may eliminate the occurrence of this spurious low-level viraemia.

  5. Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

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    Hamlyn, Elizabeth; Ewings, Fiona M; Porter, Kholoud

    2012-01-01

    OBJECTIVES: The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI). DESIGN: Two populations with protocol......VL levels, at a median of 50 (95% CI 48-51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL≥400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26-0.64) log(10) copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks...

  6. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

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    Soulie, Cathia; Grudé, Maxime; Descamps, Diane; Amiel, Corinne; Morand-Joubert, Laurence; Raymond, Stéphanie; Pallier, Coralie; Bellecave, Pantxika; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Montes, Brigitte; Barin, Francis; Ferré, Virginie; Jeulin, Hélène; Alloui, Chakib; Yerly, Sabine; Signori-Schmuck, Anne; Guigon, Aurélie; Fafi-Kremer, Samira; Haïm-Boukobza, Stéphanie; Mirand, Audrey; Maillard, Anne; Vallet, Sophie; Roussel, Catherine; Assoumou, Lambert; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Geneviève

    2017-08-01

    HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

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    Baroncelli, Silvia; Pirillo, Maria F.; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Antoni, Anna Degli; Galluzzo, Clementina M.; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-01-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According ...

  8. Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India

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    Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita

    2012-01-01

    Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790

  9. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

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    Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

    2016-03-03

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

  10. Impact of collection method on assessment of semen HIV RNA viral load.

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    Brendan J W Osborne

    Full Text Available The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load.Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples.The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.

  11. Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly.

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    Sardo, Luca; Hatch, Steven C; Chen, Jianbo; Nikolaitchik, Olga; Burdick, Ryan C; Chen, De; Westlake, Christopher J; Lockett, Stephen; Pathak, Vinay K; Hu, Wei-Shau

    2015-11-01

    To increase our understanding of the events that lead to HIV-1 genome packaging, we examined the dynamics of viral RNA and Gag-RNA interactions near the plasma membrane by using total internal reflection fluorescence microscopy. We labeled HIV-1 RNA with a photoconvertible Eos protein via an RNA-binding protein that recognizes stem-loop sequences engineered into the viral genome. Near-UV light exposure causes an irreversible structural change in Eos and alters its emitted fluorescence from green to red. We studied the dynamics of HIV-1 RNA by photoconverting Eos near the plasma membrane, and we monitored the population of photoconverted red-Eos-labeled RNA signals over time. We found that in the absence of Gag, most of the HIV-1 RNAs stayed near the plasma membrane transiently, for a few minutes. The presence of Gag significantly increased the time that RNAs stayed near the plasma membrane: most of the RNAs were still detected after 30 min. We then quantified the proportion of HIV-1 RNAs near the plasma membrane that were packaged into assembling viral complexes. By tagging Gag with blue fluorescent protein, we observed that only a portion, ∼13 to 34%, of the HIV-1 RNAs that reached the membrane were recruited into assembling particles in an hour, and the frequency of HIV-1 RNA packaging varied with the Gag expression level. Our studies reveal the HIV-1 RNA dynamics on the plasma membrane and the efficiency of RNA recruitment and provide insights into the events leading to the generation of infectious HIV-1 virions. Nascent HIV-1 particles assemble on plasma membranes. During the assembly process, HIV-1 RNA genomes must be encapsidated into viral complexes to generate infectious particles. To gain insights into the RNA packaging and virus assembly mechanisms, we labeled and monitored the HIV-1 RNA signals near the plasma membrane. Our results showed that most of the HIV-1 RNAs stayed near the plasma membrane for only a few minutes in the absence of Gag, whereas

  12. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

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    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  13. HIV Viral Load

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    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  14. Kinetics of HIV-1 in cerebrospinal fluid and plasma in cryptococcal meningitis

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    Jorge A. Benetucci

    2012-04-01

    Full Text Available In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF and plasma in patients with cryptococcal meningitis (CM, we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy- free HIV-infected patients with CM. Samples were obtained at baseline (S1 and at the second (S2 and third (S3 weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease.

  15. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

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    Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

    2010-12-15

    Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

  16. Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India

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    Swati P Ahir

    2013-01-01

    Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit

  17. Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

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    Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

    2018-02-01

    Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

  18. Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay.

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    Natasha Gous

    Full Text Available Expansion of HIV viral load (VL testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert's random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites. Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS and whole blood, was investigated.Precision, accuracy (agreement and clinical misclassification (1000cp/ml of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155 and Abbott HIV-1 RT (n = 145. Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145 and whole blood (n = 147.Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42 and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32-0.37logcp/ml and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh and Abbott HIV-1 RT (frozen, respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument.The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services.

  19. HIV Viral Load: MedlinePlus Lab Test Information

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    ... this page: https://medlineplus.gov/labtests/hivviralload.html HIV Viral Load To use the sharing features on this page, please enable JavaScript. What is an HIV Viral Load? An HIV viral load is a ...

  20. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  1. HIV-1 viral load measurement in venous blood and fingerprick blood using Abbott RealTime HIV-1 DBS assay.

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    Tang, Ning; Pahalawatta, Vihanga; Frank, Andrea; Bagley, Zowie; Viana, Raquel; Lampinen, John; Leckie, Gregor; Huang, Shihai; Abravaya, Klara; Wallis, Carole L

    2017-07-01

    HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×10 7 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×10 7 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an

  2. Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

    Science.gov (United States)

    Mengoli, Carlo; Andreis, Samantha; Scaggiante, Renzo; Cruciani, Mario; Bosco, Oliviero; Ferretto, Roberto; Leoni, Davide; Maffongelli, Gaetano; Basso, Monica; Torti, Carlo; Sarmati, Loredana; Andreoni, Massimo; Palù, Giorgio; Parisi, Saverio Giuseppe

    2017-01-01

    To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log 10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log 10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log 10 HIV RNA at T0 on log 10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log 10 HIV RNA at T0 (P = 0.003) was apparent. PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1 Evaluation of a molecular assay for determining viral load on HIV-1 antibody negative patients

    Directory of Open Access Journals (Sweden)

    José Moreira Pereira

    2002-01-01

    Full Text Available O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika foi repetidamente positiva na ausência de anticorpos para HIV e chama atenção para o fato de que a carga viral abaixo de 10 mil cópias/ml é de difícil interpretação, como tem sido assinalado em numerosos artigos, em que foram utilizadas outras metodologias.The plasma viral load test for HIV-1,a exquisitely high sensitive assay, were neither developed nor evaluated for the diagnosis of primary HIV infection; therefore, their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. This article reported four cases of false positive results obtained by using NucliSens viral load assay (Organon Teknika and emphasize the importance that low positive plasma viral load (< 10 000 copies/ml may be difficult to interpret how has been assinalated in numerous articles in the medical literature, using other methodologies.

  4. Plasma HIV-1 RNA viral load rebound among people who inject drugs receiving antiretroviral therapy (ART) in a Canadian setting: an ethno-epidemiological study.

    Science.gov (United States)

    Small, Will; Milloy, M J; McNeil, Ryan; Maher, Lisa; Kerr, Thomas

    2016-01-01

    People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada. Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant's HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound. Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation. This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.

  5. Visualization of Content Release from Cell Surface-Attached Single HIV-1 Particles Carrying an Extra-Viral Fluorescent pH-Sensor.

    Science.gov (United States)

    Sood, Chetan; Marin, Mariana; Mason, Caleb S; Melikyan, Gregory B

    2016-01-01

    HIV-1 fusion leading to productive entry has long been thought to occur at the plasma membrane. However, our previous single virus imaging data imply that, after Env engagement of CD4 and coreceptors at the cell surface, the virus enters into and fuses with intracellular compartments. We were unable to reliably detect viral fusion at the plasma membrane. Here, we implement a novel virus labeling strategy that biases towards detection of virus fusion that occurs in a pH-neutral environment-at the plasma membrane or, possibly, in early pH-neutral vesicles. Virus particles are co-labeled with an intra-viral content marker, which is released upon fusion, and an extra-viral pH sensor consisting of ecliptic pHluorin fused to the transmembrane domain of ICAM-1. This sensor fully quenches upon virus trafficking to a mildly acidic compartment, thus precluding subsequent detection of viral content release. As an interesting secondary observation, the incorporation of the pH-sensor revealed that HIV-1 particles occasionally shuttle between neutral and acidic compartments in target cells expressing CD4, suggesting a small fraction of viral particles is recycled to the plasma membrane and re-internalized. By imaging viruses bound to living cells, we found that HIV-1 content release in neutral-pH environment was a rare event (~0.4% particles). Surprisingly, viral content release was not significantly reduced by fusion inhibitors, implying that content release was due to spontaneous formation of viral membrane defects occurring at the cell surface. We did not measure a significant occurrence of HIV-1 fusion at neutral pH above this defect-mediated background loss of content, suggesting that the pH sensor may destabilize the membrane of the HIV-1 pseudovirus and, thus, preclude reliable detection of single virus fusion events at neutral pH.

  6. Visualization of Content Release from Cell Surface-Attached Single HIV-1 Particles Carrying an Extra-Viral Fluorescent pH-Sensor.

    Directory of Open Access Journals (Sweden)

    Chetan Sood

    Full Text Available HIV-1 fusion leading to productive entry has long been thought to occur at the plasma membrane. However, our previous single virus imaging data imply that, after Env engagement of CD4 and coreceptors at the cell surface, the virus enters into and fuses with intracellular compartments. We were unable to reliably detect viral fusion at the plasma membrane. Here, we implement a novel virus labeling strategy that biases towards detection of virus fusion that occurs in a pH-neutral environment-at the plasma membrane or, possibly, in early pH-neutral vesicles. Virus particles are co-labeled with an intra-viral content marker, which is released upon fusion, and an extra-viral pH sensor consisting of ecliptic pHluorin fused to the transmembrane domain of ICAM-1. This sensor fully quenches upon virus trafficking to a mildly acidic compartment, thus precluding subsequent detection of viral content release. As an interesting secondary observation, the incorporation of the pH-sensor revealed that HIV-1 particles occasionally shuttle between neutral and acidic compartments in target cells expressing CD4, suggesting a small fraction of viral particles is recycled to the plasma membrane and re-internalized. By imaging viruses bound to living cells, we found that HIV-1 content release in neutral-pH environment was a rare event (~0.4% particles. Surprisingly, viral content release was not significantly reduced by fusion inhibitors, implying that content release was due to spontaneous formation of viral membrane defects occurring at the cell surface. We did not measure a significant occurrence of HIV-1 fusion at neutral pH above this defect-mediated background loss of content, suggesting that the pH sensor may destabilize the membrane of the HIV-1 pseudovirus and, thus, preclude reliable detection of single virus fusion events at neutral pH.

  7. Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: an observational study

    Directory of Open Access Journals (Sweden)

    Sangsari Sassan

    2012-01-01

    Full Text Available Abstract Background Despite the availability of antiretroviral therapy (ART, suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART. Methods Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA Results Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85% achieved a plasma HIV RNA Conclusions In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.

  8. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    International Nuclear Information System (INIS)

    Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

    2015-01-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4"+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4"+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4"+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation (IR) increases

  9. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Iordanskiy, Sergey [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Van Duyne, Rachel [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Romerio, Fabio [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Kashanchi, Fatah, E-mail: fkashanc@gmu.edu [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States)

    2015-11-15

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation

  10. Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load.

    Science.gov (United States)

    Karlsson, Ulf; Antonsson, Liselotte; Ljungberg, Bengt; Medstrand, Patrik; Esbjörnsson, Joakim; Jansson, Marianne; Gisslen, Magnus

    2012-09-10

    To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4 T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4 T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4 T-cell counts. The use of other alternative coreceptors was less pronounced. Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4 T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.

  11. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Directory of Open Access Journals (Sweden)

    Stacey X Xu

    Full Text Available HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  12. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Science.gov (United States)

    Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D

    2018-01-01

    HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  13. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

    Science.gov (United States)

    Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H

    2000-10-20

    To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

  14. The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States

    Directory of Open Access Journals (Sweden)

    Jordan E. Cates

    2015-01-01

    Full Text Available Background. To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss among HIV-infected women enrolled in the Women’s Interagency HIV Study between 1994 and 2013. Methods. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART to conception, and log10 copy-years viremia in the two years before conception. Results. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI: 0.99, 2.56 times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs: 0.80 (95% CI: 0.69, 0.92 and 1.00 (95% CI: 0.90, 1.11, resp.. Conclusions. Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

  15. The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States.

    Science.gov (United States)

    Cates, Jordan E; Westreich, Daniel; Edmonds, Andrew; Wright, Rodney L; Minkoff, Howard; Colie, Christine; Greenblatt, Ruth M; Cejtin, Helen E; Karim, Roksana; Haddad, Lisa B; Kempf, Mirjam-Colette; Golub, Elizabeth T; Adimora, Adaora A

    2015-01-01

    To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

  16. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Anusha Ande

    Full Text Available Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART. Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a HIV negative non-smokers, b HIV positive non-smokers, c HIV negative mild-to-moderate smokers, and d HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest

  17. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.

  18. Relationship of HIV Reservoir Characteristics with Immune Status and Viral Rebound Kinetics in an HIV Therapeutic Vaccine Study

    Science.gov (United States)

    Li, Jonathan Z.; Heisey, Andrea; Ahmed, Hayat; Wang, Hongying; Zheng, Lu; Carrington, Mary; Wrin, Terri; Schooley, Robert T.; Lederman, Michael M.; Kuritzkes, Daniel R.

    2014-01-01

    Objectives To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics. Design Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine. Methods Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay. Results At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01). Conclusions Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics. PMID:25254301

  19. Preanalytic process linked to spuriously elevated HIV viral loads: improvement on an FDA-approved process.

    Science.gov (United States)

    Procop, Gary W; Taege, Alan J; Starkey, Colleen; Tungsiripat, Marisa; Warner, Diane; Schold, Jesse D; Yen-Lieberman, Belinda

    2017-09-01

    The processing of specimens often occurs in a central processing area within laboratories. We demonstrated that plasma centrifuged in the central laboratory but allowed to remain within the primary tube following centrifugation was associated with spuriously elevated HIV viral loads compared with recentrifugation of the plasma just prior to testing. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

  1. Viral-Associated GN: Hepatitis C and HIV.

    Science.gov (United States)

    Kupin, Warren L

    2017-08-07

    Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

  2. Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB

    Science.gov (United States)

    ... Search The CDC Health Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB Note: Javascript is disabled or ... Other Pacific Islanders MMWR Publications HIV and AIDS Viral Hepatitis STDs Tuberculosis Training and Networking Resources Call for ...

  3. Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa.

    Science.gov (United States)

    Petersen, Maya; Balzer, Laura; Kwarsiima, Dalsone; Sang, Norton; Chamie, Gabriel; Ayieko, James; Kabami, Jane; Owaraganise, Asiphas; Liegler, Teri; Mwangwa, Florence; Kadede, Kevin; Jain, Vivek; Plenty, Albert; Brown, Lillian; Lavoy, Geoff; Schwab, Joshua; Black, Douglas; van der Laan, Mark; Bukusi, Elizabeth A; Cohen, Craig R; Clark, Tamara D; Charlebois, Edwin; Kamya, Moses; Havlir, Diane

    2017-06-06

    Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Primary outcome was viral suppression (plasma HIV RNAHIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART. Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an

  4. Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

    Directory of Open Access Journals (Sweden)

    Maja Kiselinova

    2016-03-01

    Full Text Available The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6 between time point 1 and 2; and median of 31 days (IQR: 28-36 between time point 2 and 3. Patients were median of 6 years (IQR: 3-12 on ART, and plasma viral load (<50 copies/ml was suppressed for median of 4 years (IQR: 2-8. Total HIV-1 DNA, unspliced (us and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85, us HIV-1 RNA (p = 0.029, R² = 0.40, and VOA (p = 0.041, R2 = 0.44. Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54. The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1. Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the

  5. Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era

    Directory of Open Access Journals (Sweden)

    Aleixo Agdemir W

    2007-12-01

    Full Text Available Abstract Background In the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments. Methods A prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not. Results HIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART. Conclusion Detection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in

  6. Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

    Science.gov (United States)

    Hoffman, Jennifer C.; Anton, Peter A.; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O.

    2014-01-01

    Abstract Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (pplasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission. PMID:25209674

  7. An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy.

    Science.gov (United States)

    Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W; Palmer, Sarah

    2014-05-15

    We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.

  8. HIV and Viral Hepatitis

    Science.gov (United States)

    ... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

  9. Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

    Directory of Open Access Journals (Sweden)

    Mary S Campbell

    2011-03-01

    Full Text Available Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519 was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners.We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥ 50%. Adjudicators classified each seroconversion, finding 108 (71.5% linked, 40 (26.5% unlinked, and 3 (2.0% indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%. Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters.In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner

  10. Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification

    Science.gov (United States)

    Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

    2016-01-01

    Abstract The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS. Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined. A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL. All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1). The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens. PMID:27902602

  11. Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

    Directory of Open Access Journals (Sweden)

    Paulo Pereira Christo

    2011-08-01

    Full Text Available The question of whether HIV-1 RNA in cerebrospinal fluid (CSF is derived from viral replication in the central nervous system or simply reflects the transit of infected lymphocytes from the blood compartment has long been a matter of debate. Some studies found no correlation between CSF and plasma viral load, whereas others did. The lack of a correlation between the two compartments suggests that the presence of HIV-1 RNA is not simply due to the passive passage of the virus from blood to CSF but rather due to intrathecal replication. To evaluate the correlation between plasma and CSF HIV-1 RNA levels and to identify situations in which there is no correlation between the two compartments, seventy patients were prospectively studied. The association between CSF and plasma viral load was evaluated in the total population and in subgroups of patients with similar characteristics. A correlation between the CSF and plasma compartments was observed for patients undergoing highly active antiretroviral therapy (HAART, those with a CD4 T lymphocyte count lower than 200 cells/mm³, and those with increased CSF protein content. On the other hand, no correlation was observed for patients without adequate virological control, who had a CD4 count higher than 200 cells/mm³ and who did not use HAART. The correlation between the two compartments observed in some patients suggests that CSF HIV-1 RNA levels may reflect plasma levels in these subjects. In contrast, the lack of a correlation between the two compartments in patients who were not on HAART and who had normal CSF proteins and a poor virological control possibly indicates compartmentalization of the virus in CSF and, consequently, plasma-independent intrathecal viral replication.

  12. Dynamics of Viremia in Primary HIV-1 infection in Africans: Insights from Analyses of Host and Viral Correlates

    Science.gov (United States)

    Prentice, Heather A.; Price, Matthew A.; Porter, Travis R.; Cormier, Emmanuel; Mugavero, Michael J.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J.; Anzala, Omu; Amornkul, Pauli N.; Allen, Susan; Hunter, Eric; Kaslow, Richard A.; Gilmour, Jill; Tang, Jianming

    2014-01-01

    In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2–3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies. PMID:24418560

  13. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  14. Health Inequities and HIV, Viral Hepatitis, TB, and STDs

    Centers for Disease Control (CDC) Podcasts

    2010-09-15

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), discusses health inequities in the United States and how NCHHSTP research, policies, and programs can address them.  Created: 9/15/2010 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.   Date Released: 9/15/2010.

  15. Related factors to atazanavir plasma levels in a cohort of HIV positive individuals with undetectable viral load

    Directory of Open Access Journals (Sweden)

    Ana Júlia Luz

    Full Text Available OBJECTIVE: To evaluate the factors associated with plasma concentrations of atazanavir (ATV in a cohort of well-controlled HIV infected subjects (undetectable viremia. Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. METHODS: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm³, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. RESULTS AND DISCUSSION: Overall, 54 patients (mean age of 47 years and 50% women were included in the analysis. Those without ritonavir (unboosted atazanavir had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001 and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p < 0.05 in both cases. no statistical association was found among gender, ethnicity, age, weight, body mass index (BMI, lipid profile, and the plasma concentration of atazanavir. CONCLUSION: in summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p = 0.068.

  16. Circular viral DNA detection and junction sequence analysis from PBMC of SHIV-infected cynomolgus monkeys with undetectable virus plasma RNA

    International Nuclear Information System (INIS)

    Cara, Andrea; Maggiorella, Maria Teresa; Bona, Roberta; Sernicola, Leonardo; Baroncelli, Silvia; Negri, Donatella R.M.; Leone, Pasqualina; Fagrouch, Zahra; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

    2004-01-01

    Extrachromosomal forms of human immunodeficiency virus (HIV)-1 can be detected in peripheral blood mononuclear cell (PBMC) from HIV-infected patients in the absence of detectable viral replication and are thought to be a sign of active but cryptic virus replication. No information, however, are available on whether these forms are also present in animal models for acquired immunodeficiency syndrome (AIDS) and on their relation with other methods of detection of virus replication. To this aim, a polymerase chain reaction (PCR) approach was used to detect and analyze unintegrated circular 2-LTR-containing forms in PBMC of simian human immunodeficiency virus (SHIV)89.6P infected cynomolgus monkeys with RNA levels ranging between 1.8x10 6 and less than 50 copies/ml of plasma. 2-LTR forms were detected in 96.5% of monkeys' samples above 50 copies/ml of plasma, whereas they were present in 75.8% of monkeys' samples below 50 copies/ml of plasma. Persistence of unintegrated viral DNA in monkeys with undetectable plasma RNA could indicate either stability in non-dividing cells or ongoing low levels of viral replication in dividing cells

  17. Compartmentalization of the gut viral reservoir in HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Grant Tannika

    2007-12-01

    Full Text Available Abstract Background Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1 infection. The gut associated lymphoid tissue (GALT is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals. Results Gut biopsies (esophagus, stomach, duodenum and colorectum were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy patients. HIV-1 Nef and Reverse transcriptase (RT encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p Conclusion Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection.

  18. Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

    Science.gov (United States)

    Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

    2018-05-01

    Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

  19. Gastrointestinal viral load and enteroendocrine cell number are associated with altered survival in HIV-1 infected individuals.

    Directory of Open Access Journals (Sweden)

    Guido van Marle

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS. The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM enrolled pre-HAART (Highly Active Antiretroviral Therapy. We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum and somatostatin (duodenum and colon immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

  20. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA:Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged......Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...

  1. Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

    Science.gov (United States)

    Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

    2016-11-01

    Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

  2. Diagnosing acute HIV infection: The performance of quantitative HIV-1 RNA testing (viral load) in the 2014 laboratory testing algorithm.

    Science.gov (United States)

    Wu, Hsiu; Cohen, Stephanie E; Westheimer, Emily; Gay, Cynthia L; Hall, Laura; Rose, Charles; Hightow-Weidman, Lisa B; Gose, Severin; Fu, Jie; Peters, Philip J

    2017-08-01

    New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Vital Signs-HIV Care Saves Lives: Viral Suppression is Key

    Centers for Disease Control (CDC) Podcasts

    This podcast is based on the December 2014 CDC Vital Signs report. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.

  4. HIV Care Saves Lives: Viral Suppression is Key PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second Public Service Announcement is based on the December 2014 Vital Signs. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.

  5. A Strong Case for Viral Genetic Factors in HIV Virulence

    Directory of Open Access Journals (Sweden)

    Joshua T. Herbeck

    2011-03-01

    Full Text Available HIV infections show great variation in the rate of progression to disease, and the role of viral genetic factors in this variation had remained poorly characterized until recently. Now a series of four studies [1–4] published within a year has filled this important gap and has demonstrated a robust effect of the viral genotype on HIV virulence.

  6. Ultra-Sensitive HIV-1 Latency Viral Outgrowth Assays Using Humanized Mice.

    Science.gov (United States)

    Schmitt, Kimberly; Akkina, Ramesh

    2018-01-01

    In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral outgrowth assays (qVOA) have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been inadequate in detecting the presence of ultralow levels of latent virus in a number of patients who were initially thought to have been cured, but eventually showed viral rebound. In this context, new approaches utilizing in vivo mouse-based VOAs are promising. In the murine VOA (mVOA), large numbers of CD4 + T cells or PBMC from aviremic subjects are xenografted into immunodeficient NSG mice, whereas in the humanized mouse-based VOA (hmVOA) patient CD4 + T cell samples are injected into BLT or hu-hematopoetic stem cells (hu-HSC) humanized mice. While latent virus could be recovered in both of these systems, the hmVOA provides higher sensitivity than the mVOA using a fewer number of input cells. In contrast to the mVOA, the hmVOA provides a broader spectrum of highly susceptible HIV-1 target cells and enables newly engrafted cells to home into preformed human lymphoid organs where they can infect cells in situ after viral activation. Hu-mice also allow for both xenograft- and allograft-driven cell expansions with less severe GvH providing a longer time frame for potential viral outgrowth from cells with a delayed latent viral activation. Based on these advantages, the hmVOA has great potential in playing an important role in HIV-1 latency and cure research.

  7. Which adherence measure - self-report, clinician recorded or pharmacy refill - is best able to predict detectable viral load in a public ART programme without routine plasma viral load monitoring?

    Science.gov (United States)

    Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2016-07-01

    Combination antiretroviral therapy (cART) suppresses viral replication to an undetectable level if a sufficiently high level of adherence is achieved. We investigated which adherence measurement best distinguishes between patients with and without detectable viral load in a public ART programme without routine plasma viral load monitoring. We randomly selected 870 patients who started cART between May 2009 and April 2012 in 10 healthcare facilities in Addis Ababa, Ethiopia. Six hundred and sixty-four (76.3%) patients who were retained in HIV care and were receiving cART for at least 6 months were included and 642 had their plasma HIV-1 RNA concentration measured. Patients' adherence to cART was assessed according to self-report, clinician recorded and pharmacy refill measures. Multivariate logistic regression model was fitted to identify the predictors of detectable viremia. Model accuracy was evaluated by computing the area under the receiver operating characteristic (ROC) curve. A total of 9.2% and 5.5% of the 642 patients had a detectable viral load of ≥40 and ≥400 RNA copies/ml, respectively. In the multivariate analyses, younger age, lower CD4 cell count at cART initiation, being illiterate and widowed, and each of the adherence measures were significantly and independently predictive of having ≥400 RNA copies/ml. The ROC curve showed that these variables altogether had a likelihood of more than 80% to distinguish patients with a plasma viral load of ≥400 RNA copies/ml from those without. Adherence to cART was remarkably high. Self-report, clinician recorded and pharmacy refill non-adherence were all significantly predictive of detectable viremia. The choice for one of these methods to detect non-adherence and predict a detectable viral load can therefore be based on what is most practical in a particular setting. © 2016 John Wiley & Sons Ltd.

  8. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

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    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  9. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies.

    Directory of Open Access Journals (Sweden)

    Susanne Eriksson

    2013-02-01

    Full Text Available HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART. The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy

  10. A Pilot Study to Increase the Efficiency of HIV Outreach Testing Through the Use of Timely and Geolocated HIV Viral Load Surveillance Data

    Science.gov (United States)

    Jennings, Jacky M.; Schumacher, Christina; Perin, Jamie; Myers, Tanya; Fields, Nathan; Greiner Safi, Amelia; Chaulk, Patrick

    2018-01-01

    Background Eliminating HIV transmission in a population necessitates identifying population reservoirs of HIV infection and subgroups most likely to transmit. HIV viral load is the single most important predictor of HIV transmission. The objective of this analysis was to evaluate whether a public health practice pilot project based on community viral load resulted in increases in the proportion of time spent testing in high viral load areas (process measure) and 3 outcome measures—the number and percent of overall HIV diagnoses, new diagnoses, and high viral load positives—in one mid-Atlantic US city with a severe HIV epidemic. Methods The evaluation was conducted during three, 3-month periods for 3 years and included the use of community viral load, global positioning system tracking data, and statistical testing to evaluate the effectiveness of the pilot project. Results The proportion of time spent outreach testing in high viral load areas (69%–84%, P the overall number and percent of HIV positives ((60 (3%) to 127 (6%), P The number and percent of new diagnoses (3 (0.1%) to 6 (0.2%)) and high viral load positives (5 (0.2%) to 9 (0.4%)) increased, but the numbers were too small for statistical testing. Discussion These results suggest that using community viral load to increase the efficiency of HIV outreach testing is feasible and may be effective in identifying more HIV positives. The pilot project provides a model for other public health practice demonstration projects. PMID:29420450

  11. Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors

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    Xiaoli Zhang

    Full Text Available OBJECTIVE: One approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs. It is suspected that SP plasma has strongly neutralizing antibodies (NAb targeting specific HIV viral epitopes. METHODS: NAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from hightiter NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes. RESULTS: SPs had significantly more plasma neutralizing activity than typical progressors (TPs (p = 0.04. P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction. CONCLUSION: Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.

  12. Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

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    Vladimir Novitsky

    2011-02-01

    Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

  13. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

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    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  14. Residual viraemia in HIV-1-infected patients with plasma viral load

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, B K

    2008-01-01

    Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active......-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2...

  15. Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus-coinfected people.

    Science.gov (United States)

    Aibibula, W; Cox, J; Hamelin, A-M; Moodie, Eem; Naimi, A I; McLinden, T; Klein, M B; Brassard, P

    2018-02-01

    The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV). This study was conducted using data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model. A total of 725 HIV/HCV-coinfected people with 1973 person-visits over 3 years of follow-up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300-665] cells/μL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91-fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure. These findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV-coinfected people. © 2017 British HIV Association.

  16. Effect of Patient Navigation With or Without Financial Incentives on Viral Suppression Among Hospitalized Patients With HIV Infection and Substance Use

    Science.gov (United States)

    Metsch, Lisa R.; Feaster, Daniel J.; Gooden, Lauren; Matheson, Tim; Stitzer, Maxine; Das, Moupali; Jain, Mamta K.; Rodriguez, Allan E.; Armstrong, Wendy S.; Lucas, Gregory M.; Nijhawan, Ank E.; Drainoni, Mari-Lynn; Herrera, Patricia; Vergara-Rodriguez, Pamela; Jacobson, Jeffrey M.; Mugavero, Michael J.; Sullivan, Meg; Daar, Eric S.; McMahon, Deborah K.; Ferris, David C.; Lindblad, Robert; VanVeldhuisen, Paul; Oden, Neal; Castellón, Pedro C.; Tross, Susan; Haynes, Louise F.; Douaihy, Antoine; Sorensen, James L.; Metzger, David S.; Mandler, Raul N.; Colfax, Grant N.; del Rio, Carlos

    2017-01-01

    IMPORTANCE Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates. OBJECTIVE To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients. DESIGN, SETTING, AND PARTICIPANTS From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months. INTERVENTIONS Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment. MAIN OUTCOMES AND MEASURES The primary outcome was HIV viral suppression (≤200 copies/mL) relative to viral nonsuppression or death at the 12-month follow-up. RESULTS Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249

  17. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.

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    Sonya A MacParland

    Full Text Available Decreased hepatitis C virus (HCV clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV coinfection. The CD4+ T helper cytokines interleukin (IL-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

  18. Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion

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    de la Vega Michelle

    2011-12-01

    Full Text Available Abstract Background We recently provided evidence that HIV-1 enters HeLa-derived TZM-bl and lymphoid CEMss cells by fusing with endosomes, whereas its fusion with the plasma membrane does not proceed beyond the lipid mixing step. The mechanism of restriction of HIV-1 fusion at the cell surface and/or the factors that aid the virus entry from endosomes remain unclear. Results We examined HIV-1 fusion with a panel of target cells lines and with primary CD4+ T cells. Kinetic measurements of fusion combined with time-resolved imaging of single viruses further reinforced the notion that HIV-1 enters the cells via endocytosis and fusion with endosomes. Furthermore, we attempted to deliberately redirect virus fusion to the plasma membrane, using two experimental strategies. First, the fusion reaction was synchronized by pre-incubating the viruses with cells at reduced temperature to allow CD4 and coreceptors engagement, but not the virus uptake or fusion. Subsequent shift to a physiological temperature triggered accelerated virus uptake followed by entry from endosomes, but did not permit fusion at the cell surface. Second, blocking HIV-1 endocytosis by a small-molecule dynamin inhibitor, dynasore, resulted in transfer of viral lipids to the plasma membrane without any detectable release of the viral content into the cytosol. We also found that a higher concentration of dynasore is required to block the HIV-endosome fusion compared to virus internalization. Conclusions Our results further support the notion that HIV-1 enters disparate cell types through fusion with endosomes. The block of HIV-1 fusion with the plasma membrane at a post-lipid mixing stage shows that this membrane is not conducive to fusion pore formation and/or enlargement. The ability of dynasore to interfere with the virus-endosome fusion suggests that dynamin could be involved in two distinct steps of HIV-1 entry - endocytosis and fusion within intracellular compartments.

  19. Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

    Science.gov (United States)

    García, F; Niebla, G; Romeu, J; Vidal, C; Plana, M; Ortega, M; Ruiz, L; Gallart, T; Clotet, B; Miró, J M; Pumarola, T; Gatell, J M

    1999-08-20

    To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

  20. HIV care visits and time to viral suppression, 19 U.S. jurisdictions, and implications for treatment, prevention and the national HIV/AIDS strategy.

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    H Irene Hall

    Full Text Available OBJECTIVE: Early and regular care and treatment for human immunodeficiency virus (HIV infection are associated with viral suppression, reductions in transmission risk and improved health outcomes for persons with HIV. We determined, on a population level, the association of care visits with time from HIV diagnosis to viral suppression. METHODS: Using data from 19 areas reporting HIV-related tests to national HIV surveillance, we determined time from diagnosis to viral suppression among 17,028 persons diagnosed with HIV during 2009, followed through December 2011, using data reported through December 2012. Using Cox proportional hazards models, we assessed factors associated with viral suppression, including linkage to care within 3 months of diagnosis, a goal set forth by the National HIV/AIDS Strategy, and number of HIV care visits as determined by CD4 and viral load test results, while controlling for demographic, clinical, and risk characteristics. RESULTS: Of 17,028 persons diagnosed with HIV during 2009 in the 19 areas, 76.6% were linked to care within 3 months of diagnosis and 57.0% had a suppressed viral load during the observation period. Median time from diagnosis to viral suppression was 19 months overall, and 8 months among persons with an initial CD4 count ≤ 350 cells/µL. During the first 12 months after diagnosis, persons linked to care within 3 months experienced shorter times to viral suppression (higher rate of viral suppression per unit time, hazard ratio [HR] = 4.84 versus not linked within 3 months; 95% confidence interval [CI] 4.27, 5.48. Persons with a higher number of time-updated care visits also experienced a shorter time to viral suppression (HR = 1.51 per additional visit, 95% CI 1.49, 1.52. CONCLUSIONS: Timely linkage to care and greater frequency of care visits were associated with faster time to viral suppression with implications for individual health outcomes and for secondary prevention.

  1. 78 FR 32392 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2013-05-30

    ... Resources and Services Administration CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention.../AIDS, Viral Hepatitis and other STDs, the support of health care services to persons living with HIV/AIDS, and education of health professionals and the public about HIV/AIDS, Viral Hepatitis and other...

  2. 77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2012-11-05

    ... Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment In accordance with section 10(a...--Treatment as Prevention; (2) Ryan White HIV/AIDS Program Client Level Data Update; (3) Viral Hepatitis... Person for More Information: Margie Scott-Cseh, National Center for HIV/AIDS, Viral Hepatitis, STD, and...

  3. Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

    Science.gov (United States)

    Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

    2009-01-01

    Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

  4. Comparison of the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test v1.0 with v2.0 in HIV-1 viral load quantification

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    Yi-Ching Tung

    2015-04-01

    Full Text Available Roche modified the COBAS AmpliPrep/COBAS TaqMan human immunodeficiency virus type 1 (HIV-1 test version 1.0 (CAP/CTM v1.0, resulting in the COBAS AmpliPrep/COBAS TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0. The aim of this study was to evaluate the performance of the CAP/CTM v2.0 and to compare this performance with that of the CAP/CTM v1.0. The study was conducted in a small local study group in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. A total of 86 plasma samples from HIV-1-seropositive patients were tested using the two assays. The correlation and concordance of results between the two assays were calculated. The CAP/CTM v2.0 generated higher values than did the CAP/CTM v1.0, and five samples (5.8% yielded a difference of > 1 log10 copies/mL. In addition, our data show that CAP/CTM v1.0 and CAP/CTM v2.0 yielded relatively consistent values for 23 samples with low viral loads (< 200 copies/mL. Furthermore, when viral loads were in a medium range (2–5 log10 copies/mL, the results of the two assays were more compatible. This study shows a good correlation between CAP/CTM v1.0 and v2.0 in HIV-1 viral load measurement. Further attention must be paid to those cases in which measured viral loads present larger differences between the two assays.

  5. Antibody maturation and viral diversification in HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Maria M James

    Full Text Available The Post-exposure Prophylaxis in Infants (PEPI-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488; a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54. Antibody maturation and viral diversification were examined in these women.Samples collected at enrollment (N = 2,561 and 12-24 months later (N = 1,306 were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples and the known non-recent group (43 enrollment samples, 22 follow-up samples. Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US with known recent infection (N = 102 and known non-recent infection (N = 67.In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.

  6. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load EPF-ANRS CO1).

    Science.gov (United States)

    Tubiana, Roland; Le Chenadec, Jerome; Rouzioux, Christine; Mandelbrot, Laurent; Hamrene, Karima; Dollfus, Catherine; Faye, Albert; Delaugerre, Constance; Blanche, Stephane; Warszawski, Josiane

    2010-02-15

    The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non-breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997-2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30+/-4 weeks adjusted for viral load, CD4(+) T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5-553; P<.001). Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4(+) T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.

  7. Vital Signs-HIV Care Saves Lives: Viral Suppression is Key

    Centers for Disease Control (CDC) Podcasts

    2014-11-25

    This podcast is based on the December 2014 CDC Vital Signs report. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/25/2014.

  8. HIV Care Saves Lives: Viral Suppression is Key PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2014-11-25

    This 60 second Public Service Announcement is based on the December 2014 Vital Signs. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 11/25/2014.

  9. Improving laboratory efficiencies to scale-up HIV viral load testing.

    Science.gov (United States)

    Alemnji, George; Onyebujoh, Philip; Nkengasong, John N

    2017-03-01

    Viral load measurement is a key indicator that determines patients' response to treatment and risk for disease progression. Efforts are ongoing in different countries to scale-up access to viral load testing to meet the Joint United Nations Programme on HIV and AIDS target of achieving 90% viral suppression among HIV-infected patients receiving antiretroviral therapy. However, the impact of these initiatives may be challenged by increased inefficiencies along the viral load testing spectrum. This will translate to increased costs and ineffectiveness of scale-up approaches. This review describes different parameters that could be addressed across the viral load testing spectrum aimed at improving efficiencies and utilizing test results for patient management. Though progress is being made in some countries to scale-up viral load, many others still face numerous challenges that may affect scale-up efficiencies: weak demand creation, ineffective supply chain management systems; poor specimen referral systems; inadequate data and quality management systems; and weak laboratory-clinical interface leading to diminished uptake of test results. In scaling up access to viral load testing, there should be a renewed focus to address efficiencies across the entire spectrum, including factors related to access, uptake, and impact of test results.

  10. Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.

    Science.gov (United States)

    Patterson, B K; Mosiman, V L; Cantarero, L; Furtado, M; Bhattacharya, M; Goolsby, C

    1998-04-01

    Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.

  11. Evaluation of the performance of Abbott m2000 and Roche COBAS Ampliprep/COBAS Taqman assays for HIV-1 viral load determination using dried blood spots and dried plasma spots in Kenya.

    Science.gov (United States)

    Zeh, Clement; Ndiege, Kenneth; Inzaule, Seth; Achieng, Rebecca; Williamson, John; Chih-Wei Chang, Joy; Ellenberger, Dennis; Nkengasong, John

    2017-01-01

    Routine HIV viral load testing is not widely accessible in most resource-limited settings, including Kenya. To increase access to viral load testing, alternative sample types like dried blood spots (DBS), which overcome the logistic barriers associated with plasma separation and cold chain shipment need to be considered and evaluated. The current study evaluated matched dried blood spots (DBS) and dried plasma spots (DPS) against plasma using the Abbott M 2000 (Abbott) and Roche Cobas Ampliprep/Cobas TaqMan (CAP/CTM) quantitative viral load assays in western Kenya. Matched plasma DBS and DPS were obtained from 200 HIV-1 infected antiretroviral treatment (ART)-experienced patients attending patient support centers in Western Kenya. Standard quantitative assay performance parameters with accompanying 95% confidence intervals (CI) were assessed at the assays lower detection limit (400cps/ml for CAP/CTM and 550cps/ml for Abbott) using SAS version 9.2. Receiver operating curves (ROC) were further used to assess viral-load thresholds with best assay performance (reference assay CAP/CTM plasma). Using the Abbott test, the sensitivity and specificity, respectively, for DPS were (97.3%, [95%CI: 93.2-99.2] and 98.1% [95%CI: 89.7-100]) and those for DBS (93.9% [95%CI: 88.8-97.2] and 88.0% [95%CI: 82.2-92.4]). The correlation and agreement using paired plasma and DPS/DBS were strong, with r2 = 90.5 and rc = 68.1. The Bland-Altman relative percent change was 95.3 for DPS, (95%CI: 90.4-97.7) and 73.6 (95%CI: 51.6-86.5) for DBS. Using the CAP/CTM assay, the sensitivity for DBS was significantly higher compared to DPS (100.0% [95% CI: 97.6-100.0] vs. 94.7% [95%CI: 89.8-97.7]), while the specificity for DBS was lower: 4%, [95% CI: 0.4-13.7] compared to DPS: 94.0%, [95% CI: 83.5-98.7]. When compared under different clinical relevant thresholds, the accuracy for the Abbott assay was 95% at the 1000cps/ml cut-off with a sensitivity and specificity of 96.6% [95% CI 91.8-98.7] and 90

  12. A pilot evaluation of whole blood finger-prick sampling for point-of-care HIV viral load measurement: the UNICORN study.

    Science.gov (United States)

    Fidler, Sarah; Lewis, Heather; Meyerowitz, Jodi; Kuldanek, Kristin; Thornhill, John; Muir, David; Bonnissent, Alice; Timson, Georgina; Frater, John

    2017-10-20

    There is a global need for HIV viral load point-of-care (PoC) assays to monitor patients receiving antiretroviral therapy. UNICORN was the first study of an off-label protocol using whole blood finger-prick samples tested with and without a simple three minute spin using a clinic-room microcentrifuge. Two PoC assays were evaluated in 40 HIV-positive participants, 20 with detectable and 20 with undetectable plasma viral load (pVL) (<20 copies/ml). Using 100 µl finger-prick blood samples, the Cepheid Xpert HIV-1 Viral Load and HIV-1 Qual cartridges were compared with laboratory pVL assessment (TaqMan, Roche). For participants with undetectable viraemia by TaqMan, there was poor concordance without centrifugation with the TaqMan platform with only 40% 'undetectable' using Xpert VL and 25% 'not detected' using the Qual assay. After a 3 minute spin, 100% of samples were undetectable using either assay, showing full concordance with the TaqMan assay. Defining a lower limit of detection of 1000 copies/ml when including a spin, there was 100% concordance with the TaqMan platform with strong correlation (rho 0.95 and 0.94; p < 0.0001 for both assays). When including a simple microcentrifugation step, finger-prick PoC testing was a quick and accurate approach for assessing HIV viraemia, with excellent concordance with validated laboratory approaches.

  13. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

    DEFF Research Database (Denmark)

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent

    2013-01-01

    Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA......) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study....

  14. Generation of representative primary virus isolates from blood plasma after isolation of HIV-1 with CD44 MicroBeads

    NARCIS (Netherlands)

    Cornelissen, M; Heeregrave, E.J.; Zorgdrager, F.; Pollakis, G.; Paxton, W.A.; van der Kuyl, A.C.

    2010-01-01

    Infection of cell cultures with cell-free virus isolated from HIV-infected patients is notoriously difficult and results in a loss of viral variation. Here, we describe viral sequences from PBMC, U87.CD4.CCR5 and U87.CD4.CXCR4 cell cultures and compare them to those from blood plasma from 12

  15. Self-Perceived Viral Load and Sexual Risk Behavior Among Known HIV-Positive MSM in San Francisco, 2014.

    Science.gov (United States)

    Guigayoma, John; Chen, Yea-Hung; Snowden, Jonathan M; Santos, Glenn-Milo; Hecht, Jennifer; Raymond, H Fisher

    2017-07-01

    Self-perceived viral suppression status among men who have sex with men (MSM) may impact HIV risk transmission behaviors. We conducted a 2014 cross-sectional survey of MSM in San Francisco and assessed differences in sexual risk behavior among known HIV-positive MSM based on viral suppression of HIV. We collected demographics, self-perceived viral load status, and sexual risk behavior and tested for viral load levels through laboratory assays. Men were categorized in a hierarchical schema of sexual risk behavior categories based on responses to questions regarding recent partners' HIV status, condom use, and sexual positioning. We used Fisher exact tests to assess for differences based on self-perceived viral load status. Out of a sample of 96 known HIV-positive men, 59 men self-reported an undetectable HIV viral load and 9 men self-reported a detectable viral load consented to confirmatory laboratory testing. The sample of self-reported undetectable men had gradually larger proportions of higher-risk sexual practices, whereas the sample of detectable men was evenly distributed across sexual practices. This association was not statistically significant (P = 0.91). Self-perceived viral suppression may influence sexual practices of known HIV-positive MSM, but small sample size, especially within the detectable category, hinders our ability to determine statistical significance. More research is necessary to assess how HIV-positive men account for viral load in sexual decision-making practices, and this research may inform resource allocation and clinical recommendations to maintain the health of MSM populations.

  16. Distribution of HIV RNA in CSF and Blood is linked to CD4/CD8 Ratio During Acute HIV.

    Science.gov (United States)

    Chan, Phillip; Patel, Payal; Hellmuth, Joanna; Colby, Donn J; Kroon, Eugène; Sacdalan, Carlo; Pinyakorn, Suteeraporn; Jagodzinski, Linda; Krebs, Shelly; Ananworanich, Jintanat; Valcour, Victor; Spudich, Serena

    2018-05-07

    HIV RNA levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection but their dynamics have not been characterized during acute infection. This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. CSF immune markers were compared between groups with different PCratio. 117 mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had median age 28 years and an estimated median 18 days duration of infection; forty-three (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA CSF HIV RNA and PCratio of 3.76 and 2.36 Log10 copies/mL, respectively. HIV RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (pCSF neopterin, sCD163, IL-6 and sCD14 levels (all pCSF HIV RNA and PCratio, suggesting that immune responses modulate CNS viral entry at early infection.

  17. Performance Evaluation of the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit: Comparison with the Roche COBAS® AmpliPrep/COBAS TaqMan® HIV-1 Test Ver.2.0 for Quantification of HIV-1 Viral Load in Indonesia.

    Science.gov (United States)

    Kosasih, Agus Susanto; Sugiarto, Christine; Hayuanta, Hubertus Hosti; Juhaendi, Runingsih; Setiawan, Lyana

    2017-08-08

    Measurement of viral load in human immunodeficiency virus type 1 (HIV-1) infected patients is essential for the establishment of a therapeutic strategy. Several assays based on qPCR are available for the measurement of viral load; they differ in sample volume, technology applied, target gene, sensitivity and dynamic range. The Bioneer AccuPower® HIV-1 Quantitative RT-PCR is a novel commercial kit that has not been evaluated for its performance. This study aimed to evaluate the performance of the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit. In total, 288 EDTA plasma samples from the Dharmais Cancer Hospital were analyzed with the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit and the Roche COBAS? AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0 (CAP/CTM v2.0). The performance of the Bioneer assay was then evaluated against the Roche CAP/CTM v2.0. Overall, there was good agreement between the two assays. The Bioneer assay showed significant linear correlation with CAP/CTM v2.0 (R2=0.963, plaboratories.

  18. Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

    Science.gov (United States)

    Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

    2016-07-01

    Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.

  19. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

    Science.gov (United States)

    Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

    2007-10-01

    Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

  20. Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers.

    Science.gov (United States)

    Hutin, Yvan; Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

    2017-12-15

    Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators.

  1. 78 FR 64221 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of...

    Science.gov (United States)

    2013-10-28

    ... Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of Meeting In... Administrator, HRSA, regarding activities related to prevention and control of HIV/AIDS, Viral Hepatitis and... professionals and the public about HIV/AIDS, Viral Hepatitis, and other STDs. Agenda: Agenda items include: (1...

  2. HIV-1 DNA predicts disease progression and post-treatment virological control

    Science.gov (United States)

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  3. Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

    Science.gov (United States)

    Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J

    2017-08-01

    Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

  4. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.

    Science.gov (United States)

    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M

    2014-02-01

    In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. In a prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum, and nonpregnant periods. Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower during pregnant compared with postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and nonpregnant periods (P = 0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared with nonpregnant periods. CD4 count declines among HIV-1-infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short-term impact on plasma HIV-1 RNA concentrations.

  5. A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots.

    Science.gov (United States)

    Makadzange, A Tariro; Boyd, F Kathryn; Chimukangara, Benjamin; Masimirembwa, Collen; Katzenstein, David; Ndhlovu, Chiratidzo E

    2017-07-01

    Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system. Copyright © 2017 Makadzange et al.

  6. Select neurocognitive impairment in HIV-infected women: associations with HIV viral load, hepatitis C virus, and depression, but not leukocyte telomere length.

    Directory of Open Access Journals (Sweden)

    Chantelle J Giesbrecht

    Full Text Available Through implementation of combination antiretroviral therapy (cART remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection, to characterize impairments in predominately male HIV-infected populations.Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+ women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB.On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV- women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL, a marker of cellular aging, did not significantly differ between HIV+ and HIV- women, nor was LTL associated with overall neurocognition in the HIV+ group.The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments.

  7. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected pa......The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-10 viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  8. The HIV-1 Rev/RRE system is required for HIV-1 5' UTR cis elements to augment encapsidation of heterologous RNA into HIV-1 viral particles

    Directory of Open Access Journals (Sweden)

    Ma Hong

    2011-06-01

    Full Text Available Abstract Background The process of HIV-1 genomic RNA (gRNA encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ. Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site from the 5' untranslated region (UTR. Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ. Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons; however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into

  9. Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

    Science.gov (United States)

    Bagnoli, F.; Liò, P.; Sguanci, L.

    2006-07-01

    The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, which describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasispeciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.

  10. Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda.

    Science.gov (United States)

    Balinda, Sheila N; Ondoa, Pascale; Obuku, Ekwaro A; Kliphuis, Aletta; Egau, Isaac; Bronze, Michelle; Kasambula, Lordwin; Schuurman, Rob; Spieker, Nicole; Rinke de Wit, Tobias F; Kityo, Cissy

    2016-01-01

    WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda. We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml). 496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%-87.1%), 93% specificity (95% CI: 89.7%-96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively. VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS.

  11. Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda.

    Directory of Open Access Journals (Sweden)

    Sheila N Balinda

    Full Text Available WHO recommends regular viral load (VL monitoring of patients on antiretroviral therapy (ART for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS. We evaluated a simple, low-cost, qualitative viral-failure assay (VFA on dried blood spots (DBS in three clinical settings in Uganda.We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml.496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%-87.1%, 93% specificity (95% CI: 89.7%-96.4%, 89.3% accuracy (95% CI: 85%-92% and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively.VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS.

  12. HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

    Science.gov (United States)

    Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

    2008-01-01

    Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

  13. Different patterns of HIV-1 DNA after therapy discontinuation

    Directory of Open Access Journals (Sweden)

    Ghinelli Florio

    2005-09-01

    Full Text Available Abstract Background By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 – 24 weeks to study the possible relationship between DNA and RNA viral load. Methods The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load. Results Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. Conclusion Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.

  14. Integrase inhibitors in late pregnancy and rapid HIV viral load reduction.

    Science.gov (United States)

    Rahangdale, Lisa; Cates, Jordan; Potter, JoNell; Badell, Martina L; Seidman, Dominika; Miller, Emilly S; Coleman, Jenell S; Lazenby, Gweneth B; Levison, Judy; Short, William R; Yawetz, Sigal; Ciaranello, Andrea; Livingston, Elizabeth; Duthely, Lunthita; Rimawi, Bassam H; Anderson, Jean R; Stringer, Elizabeth M

    2016-03-01

    Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1 infected women

    Science.gov (United States)

    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M.

    2014-01-01

    Background In HIV-1 infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy (ART), it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. Methods In a prospective study among 2269 HIV-1 infected ART-naïve women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum and non-pregnant periods. Results Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% CI 39-73) cells/mm3 lower during pregnant compared to non-pregnant periods and 70 (95% CI 53-88) cells/mm3 lower during pregnant compared to postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and non-pregnant periods (p=0.9) or pregnant and postpartum periods (p=0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared to non-pregnant periods. Conclusion CD4 count declines among HIV-1 infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short term impact on plasma HIV-1 RNA concentrations. PMID:24442226

  16. Short communication: identification of a novel HIV type 1 subtype H/J recombinant in Canada with discordant HIV viral load (RNA) values in three different commercial assays.

    Science.gov (United States)

    Kim, John E; Beckthold, Brenda; Chen, Zhaoxia; Mihowich, Jennifer; Malloch, Laurie; Gill, Michael John

    2007-11-01

    The presence of HIV-1 non-B subtypes is increasing worldwide. This poses challenges to commercial diagnostic and viral load (RNA) monitoring tests that are predominantly based on HIV-1 subtype B strains. Based on phylogenetic analysis of the gag, pol, and env gene regions, we describe the first HIV-1 H/J recombinant in Canada that presented divergent viral load values. DNA sequence analysis of the gag gene region further revealed that genetic diversity between this H/J recombinant and the primers and probes used in the bio-Merieux Nuclisens HIV-1 QT (Nuclisens) and Roche Amplicor Monitor HIV-1, v1.5 (Monitor) viral RNA assays can erroneously lead to undetectable viral load values. This observation appears to be more problematic in the Nuclisens assay. In light of increasing genetic diversity in HIV worldwide we recommend that DNA sequencing of HIV, especially in the gag gene region targeted by primers and probes used in molecular diagnostic and viral load tests, be incorporated into clinical monitoring practices.

  17. Health Inequities and HIV, Viral Hepatitis, TB, and STDs

    Centers for Disease Control (CDC) Podcasts

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), discusses health inequities in the United States and how NCHHSTP research, policies, and programs can address them.

  18. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment

    Directory of Open Access Journals (Sweden)

    Monajemi Mahdis

    2012-04-01

    Full Text Available Abstract The enzyme APOBEC3G (A3G mutates the human immunodeficiency virus (HIV genome by converting deoxycytidine (dC to deoxyuridine (dU on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.

  19. Social Capital, Depressive Symptoms, and HIV Viral Suppression Among Young Black, Gay, Bisexual and Other Men Who Have Sex with Men Living with HIV.

    Science.gov (United States)

    Hussen, Sophia A; Easley, Kirk A; Smith, Justin C; Shenvi, Neeta; Harper, Gary W; Camacho-Gonzalez, Andres F; Stephenson, Rob; Del Rio, Carlos

    2018-04-04

    Social capital, the sum of an individual's resource-containing social network connections, has been proposed as a facilitator of successful HIV care engagement. We explored relationships between social capital, psychological covariates (depression, stigma and internalized homonegativity), and viral suppression in a sample of young Black gay, bisexual and other men who have sex with men (YB-GBMSM). We recruited 81 HIV-positive YB-GBMSM 18-24 years of age from a clinic setting. Participants completed a cross-sectional survey, and HIV-1 viral load (VL) measurements were extracted from the medical record. Sixty-five percent (65%) were virally suppressed (HIV-1 VL ≤ 40 copies/ml). Forty-seven percent (47%) had a positive depression screen. Depressive symptoms affected viral suppression differently in YB-GBMSM with lower vs. higher social capital (p = 0.046, test for statistical interaction between depression and social capital). The odds of viral suppression among YB-GBMSM with lower social capital was 93% lower among those with depressive symptoms (OR 0.07, p = 0.002); however, there was no association between depressive symptoms and viral suppression among those with higher social capital. Our results suggest that social capital may buffer the strong negative effects of depressive symptoms on clinical outcomes in YB-GBMSM living with HIV. In addition to treating depression, there is a role for interventions to augment social capital among YB-GBMSM living with HIV as a strategy for enhancing care engagement.

  20. Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification: A laboratory assessment of 3 commercial assays.

    Science.gov (United States)

    Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

    2016-11-01

    The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.

  1. Stem cell gene therapy for HIV: strategies to inhibit viral entry and replication.

    Science.gov (United States)

    DiGiusto, David L

    2015-03-01

    Since the demonstration of a cure of an HIV+ patient with an allogeneic stem cell transplant using naturally HIV-resistant cells, significant interest in creating similar autologous products has fueled the development of a variety of "cell engineering" approaches to stem cell therapy for HIV. Among the more well-studied strategies is the inhibition of viral entry through disruption of expression of viral co-receptors or through competitive inhibitors of viral fusion with the cell membrane. Preclinical evaluation of these approaches often starts in vitro but ultimately is tested in animal models prior to clinical implementation. In this review, we trace the development of several key approaches (meganucleases, short hairpin RNA (shRNA), and fusion inhibitors) to modification of hematopoietic stem cells designed to impart resistance to HIV to their T-cell and monocytic progeny. The basic evolution of technologies through in vitro and in vivo testing is discussed as well as the pros and cons of each approach and how the addition of postentry inhibitors may enhance the overall antiviral efficacy of these approaches.

  2. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Anthony M. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Cheung, Pamela [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Swartz, Talia H.; Li, Hongru [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Tsibane, Tshidi [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Durham, Natasha D. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Basler, Christopher F. [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Felsenfeld, Dan P. [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Chen, Benjamin K., E-mail: benjamin.chen@mssm.edu [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States)

    2016-03-15

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.

  3. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    International Nuclear Information System (INIS)

    Esposito, Anthony M.; Cheung, Pamela; Swartz, Talia H.; Li, Hongru; Tsibane, Tshidi; Durham, Natasha D.; Basler, Christopher F.; Felsenfeld, Dan P.; Chen, Benjamin K.

    2016-01-01

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.

  4. Suppression of HIV-1 viral load after multiple changes in high active ...

    African Journals Online (AJOL)

    1-infected patients. However, the virus persists ... chronological changes in HIV viral load and CD4+ T-cell count, and treatment outcomes of multiple combinations of .... Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the ...

  5. GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

    Science.gov (United States)

    Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

    2017-07-21

    Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

  6. Evaluation of a cost effective in-house method for HIV-1 drug resistance genotyping using plasma samples.

    Directory of Open Access Journals (Sweden)

    Devidas N Chaturbhuj

    Full Text Available OBJECTIVES: Validation of a cost effective in-house method for HIV-1 drug resistance genotyping using plasma samples. DESIGN: The validation includes the establishment of analytical performance characteristics such as accuracy, reproducibility, precision and sensitivity. METHODS: The accuracy was assessed by comparing 26 paired Virological Quality Assessment (VQA proficiency testing panel sequences generated by in-house and ViroSeq Genotyping System 2.0 (Celera Diagnostics, US as a gold standard. The reproducibility and precision were carried out on five samples with five replicates representing multiple HIV-1 subtypes (A, B, C and resistance patterns. The amplification sensitivity was evaluated on HIV-1 positive plasma samples (n = 88 with known viral loads ranges from 1000-1.8 million RNA copies/ml. RESULTS: Comparison of the nucleotide sequences generated by ViroSeq and in-house method showed 99.41±0.46 and 99.68±0.35% mean nucleotide and amino acid identity respectively. Out of 135 Stanford HIVdb listed HIV-1 drug resistance mutations, partial discordance was observed at 15 positions and complete discordance was absent. The reproducibility and precision study showed high nucleotide sequence identities i.e. 99.88±0.10 and 99.82±0.20 respectively. The in-house method showed 100% analytical sensitivity on the samples with HIV-1 viral load >1000 RNA copies/ml. The cost of running the in-house method is only 50% of that for ViroSeq method (112$ vs 300$, thus making it cost effective. CONCLUSIONS: The validated cost effective in-house method may be used to collect surveillance data on the emergence and transmission of HIV-1 drug resistance in resource limited countries. Moreover, the wide applications of a cost effective and validated in-house method for HIV-1 drug resistance testing will facilitate the decision making for the appropriate management of HIV infected patients.

  7. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  8. THE POPULATION IMPACT OF ELIMINATING HOMELESSNESS ON HIV VIRAL SUPPRESSION AMONG PEOPLE WHO USE DRUGS

    Science.gov (United States)

    Marshall, Brandon D.L.; Elston, Beth; Dobrer, Sabina; Parashar, Surita; Hogg, Robert S.; Montaner, Julio S.G.; Kerr, Thomas; Wood, Evan; Milloy, M-J

    2015-01-01

    Objective We sought to estimate the change in viral suppression prevalence if homelessness were eliminated from a population of HIV-infected people who use drugs (PWUD). Design Community-recruited prospective cohort of HIV-infected PWUD in Vancouver, Canada. Behavioral information was collected at baseline and linked to a province-wide HIV/AIDS treatment database. The primary outcome was viral suppression (<50 copies/mL) measured during subsequent routine clinical care. Methods We employed an imputation-based marginal modelling approach. First, we used modified Poisson regression to obtain effect estimates (adjusting for sociodemographics, substance use, addiction treatment, and other confounders). Then, we imputed an outcome probability for each individual while manipulating the exposure (homelessness). Population viral suppression prevalence under realized and “housed” scenarios were obtained by averaging these probabilities across the population. Bootstrapping was conducted to calculate 95% confidence limits. Results Of 706 individuals interviewed between January 2005 and December 2015, the majority was male (66.0%), of Caucasian race/ethnicity (55.1%), and had a history of injection (93.6%). At first study visit, 223 (31.6%) reported recent homelessness, and 37.8% were subsequently identified as virally suppressed. Adjusted marginal models estimated a 15.1% relative increase (95%CI: 9.0%, 21.7%) in viral suppression in the entire population—to 43.5% (95%CI: 39.4%, 48.2%)—if all homeless individuals were housed. Among those homeless, eliminating this exposure would increase viral suppression from 22.0% to 40.1% (95%CI: 35.1%, 46.1%), an 82.3% relative increase. Conclusions Interventions to house homeless, HIV-positive individuals who use drugs could significantly increase population viral suppression. Such interventions should be implemented as a part of renewed HIV/AIDS prevention and treatment efforts. PMID:26636924

  9. Durable Viral Suppression and Transmission Risk Potential Among Persons With Diagnosed HIV Infection: United States, 2012-2013.

    Science.gov (United States)

    Crepaz, Nicole; Tang, Tian; Marks, Gary; Mugavero, Michael J; Espinoza, Lorena; Hall, H Irene

    2016-10-01

    We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV)-diagnosed persons in care. Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential. Two-thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

  11. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  13. Control of HIV-1 in Elite Suppressors despite Ongoing Replication and Evolution in Plasma Virus▿

    Science.gov (United States)

    O'Connell, Karen A.; Brennan, Timothy P.; Bailey, Justin R.; Ray, Stuart C.; Siliciano, Robert F.; Blankson, Joel N.

    2010-01-01

    A subset of HIV-1-infected patients known as elite controllers or suppressors (ES) control the virus naturally. We have previously demonstrated sequence discordance between proviral and plasma gag clones in ES, much of which can be attributed to selective pressure from the host (J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, J. Exp. Med. 203:1357-1369, 2006). However, it is not clear whether ongoing viral replication continues in ES once the control of viremia has been established or whether selective pressure impacts this evolution. The cytotoxic T-lymphocyte (CTL) response in ES often targets Gag and frequently is superior to that of HIV-1 progressors, partially due to the HLA class I alleles B*57/5801 and B*27, which are overrepresented in ES. We therefore examined longitudinal plasma and proviral gag sequences from HLA-B*57/5801 and -B*27 ES. Despite the highly conserved nature of gag, we observed clear evidence of evolution in the plasma virus, largely due to synonymous substitutions. In contrast, evolution was rare in proviral clones, suggesting that ongoing replication in ES does not permit the significant reseeding of the latent reservoir. Interestingly, there was little continual evolution in CTL epitopes, and we detected de novo CTL responses to autologous viral mutants. Thus, some ES control viremia despite ongoing replication and evolution. PMID:20444904

  14. Ethnicity predicts viral rebound after travel to the tropics in HIV-infected travelers to the tropics in the Swiss HIV Cohort Study.

    Science.gov (United States)

    Gebreselassie, H M; Kraus, D; Fux, C A; Haubitz, S; Scherrer, A; Hatz, C; Veit, O; Stoeckle, M; Fehr, J; de Lucia, S; Cavassini, M; Bernasconi, E; Schmid, P; Furrer, H; Staehelin, C

    2017-09-01

    The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African (SSA) patients (OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53-2.61). Region of origin is the main risk factor for viral rebound

  15. Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression.

    Science.gov (United States)

    Adams, Joëlla W; Brady, Kathleen A; Michael, Yvonne L; Yehia, Baligh R; Momplaisir, Florence M

    2015-12-15

    Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV-infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (≥ 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (≥ 1 CD4 count or VL test in each 6-month interval of the period with ≥ 60 days between tests) and viral suppression (VL ≤ 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Lacour Nedra

    2008-07-01

    Full Text Available Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4% shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.

  17. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2014].

    Science.gov (United States)

    Medina González, Rafael; Orta Mira, Nieves; Guna Serrano, María Del Remedio; Latorre Martínez, José-Carlos; Gopegui, Enrique Ruiz de; Rosario Ovies, María; Poveda, Marta; Gimeno Cardona, Concepción

    2016-07-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. Impact of Antiretroviral Regimens on CSF Viral Escape in a Prospective Multicohort Study of ART-Experienced HIV-1 Infected Adults in the United States.

    Science.gov (United States)

    Mukerji, Shibani S; Misra, Vikas; Lorenz, David R; Uno, Hajime; Morgello, Susan; Franklin, Donald; Ellis, Ronald J; Letendre, Scott; Gabuzda, Dana

    2018-04-03

    Cerebrospinal fluid (CSF) viral escape occurs in 4-20% of HIV-infected adults, yet the impact of antiretroviral therapy (ART) on CSF escape is unclear. Prospective study of 1063 participants with baseline plasma viral load (VL) ≤400 copies/ml between 2005-2016. Odds ratio for ART regimens (PI with nucleoside reverse transcriptase inhibitor [PI+NRTI] versus other ART) and CSF escape was estimated using mixed-effects models. Drug resistance mutation frequencies were calculated. Baseline mean age was 46, median plasma VL, CD4 nadir, and CD4 count were 50 copies/mL, 88 cells/μL, and 424 cells/μL, respectively; 48% on PI+NRTI, 33% on non-NRTI, and 6% on integrase inhibitors. During median follow-up of 4.4 years, CSF escape occurred in 77 participants (7.2%). PI+NRTI use was an independent predictor of CSF escape (OR 3.1 [95% CI 1.8-5.0]) in adjusted analyses and models restricted to plasma VL ≤50 copies/ml (pCSF viral escape than non-ATV PI+NRTI regimens. Plasma and CSF M184V/I combined with thymidine-analog mutations were more frequent in CSF escape versus no escape (23% vs. 2.3%). Genotypic susceptibility score-adjusted CNS penetration-effectiveness (CPE) values were calculated for CSF escape with M184V/I mutations (n=34). Adjusted CPE values were low (CSF and plasma in 27 (79%) and 13 (38%), respectively, indicating suboptimal CNS drug availability. PI+NRTI regimens are independent predictors of CSF escape in HIV-infected adults. Reduced CNS ART bioavailability may predispose to CSF escape in patients with M184V/I mutations. Optimizing ART regimens may reduce risk of CSF escape.

  19. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    International Nuclear Information System (INIS)

    Ebina, Hirotaka; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-01-01

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  20. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Ebina, Hirotaka, E-mail: hebina@virus.kyoto-u.ac.jp; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-05-25

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  1. Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity.

    Science.gov (United States)

    Chung, Amy; Makuba, Jenniffer M; Ndlovu, Bongiwe; Licht, Anna; Robinson, Hannah; Ramlakhan, Yathisha; Ghebremichael, Musie; Reddy, Tarylee; Goulder, Philip; Walker, Bruce; Ndung'u, Thumbi; Alter, Galit

    2018-04-03

    Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively. p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4 counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles. p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

  2. Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 Subtype C infected patients in Northern India

    Science.gov (United States)

    Agarwal, Atima; Sankaran, Sumathi; Vajpayee, Madhu; Sreenivas, V; Seth, Pradeep; Dandekar, Satya

    2014-01-01

    Background Assays with specificity and cost effectiveness are needed for the measurement of HIV-1 burden to monitor disease progression or response to anti-retroviral therapy (ART) in HIV-1 subtype C infected patients. Objectives The objective of this study was to develop and validate an affordable; one step Real-Time RT-PCR assay with high specificity and sensitivity to measure plasma HIV-1 loads in HIV-1 subtype C infected patients. Results We developed an RT-PCR assay to detect and quantitate plasma HIV-1 levels in HIV-1 subtype C infected patients. An inverse correlation between plasma viral loads (PVL) and CD4+ T-cell numbers was detected at all CDC stages. Significant correlations were found between CD8+ T-cell activation and PVL, as well as with the clinical and immunological status of the patients. Conclusions The RT-PCR assay provides a sensitive method to measure PVL in HIV-1 subtype C infected patients. Viral loads correlated with immune activation and can be used to monitor HIV care in India. PMID:17962068

  3. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations...

  4. High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

    Directory of Open Access Journals (Sweden)

    Grinsztejn Beatriz

    2010-12-01

    Full Text Available Abstract Background Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL and tegumentary leishmaniasis (ATL have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3. Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

  5. Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission

    Science.gov (United States)

    Herbeck, Joshua T.; Müller, Viktor; Maust, Brandon S.; Ledergerber, Bruno; Torti, Carlo; Di Giambenedetto, Simona; Gras, Luuk; Günthard, Huldrych F.; Jacobson, Lisa P.; Mullins, James I.; Gottlieb, Geoffrey S.

    2013-01-01

    Objective The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results. Design We conducted a meta-analysis of changes in baseline CD4+ T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence. Methods We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4+ T-cell counts (21 052 total individuals), and eight studies of trends in set point viral loads (10 785 total individuals), spanning the years 1984–2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4+ T-cell counts. Results Baseline CD4+ T-cell counts showed a summary trend of decreasing cell counts [effect=−4.93 cells/µl per year, 95% confidence interval (CI) −6.53 to −3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect=0.013 log10 copies/ml per year, 95% CI −0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. Conclusion Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4+ T cells loss of approximately 148 cells/µl and a gain of 0.39 log10 copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk. PMID:22089381

  6. PRACTICE OF USING VIRAL PROTEASE INHIBITORS IN CHILDREN WITH HIV INFECTION

    Directory of Open Access Journals (Sweden)

    V.B. Denisenko

    2010-01-01

    Full Text Available Selection of the most effective and safest high-active antiretroviral therapies is a critical issue faced by modern HIV medicine. Authors studied 28 children with HIV infection aged from 3 to 7 divided into two groups administered a combination of two HIV reverse transcriptase nucleoside inhibitors with viral protease nelfinavir inhibitors (n = 13 and lopinavir/ritonavir (n = 15. The subjects in both groups demonstrated a decreased frequency of HIV-associated symptoms and opportunistic infections, positive dynamics of immunological indicators, suppression of HIV replication. When lopinavir/ritonavir was administered, there was more even better dynamics in clinical, immunological and virologic parameters, which allows this medication to be recommended as a antiretroviral therapy for children. Key words: HIV infection, lopinavir/ritonavir, nelfinavir, children. (Pediatric Pharmacology. – 2010; 7(1:62-67

  7. Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months

    DEFF Research Database (Denmark)

    Katzenstein, T.; Ullum, H.; Røge, B.T.

    2003-01-01

    OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of

  8. Influence of Jail Incarceration and Homelessness Patterns on Engagement in HIV Care and HIV Viral Suppression among New York City Adults Living with HIV/AIDS.

    Directory of Open Access Journals (Sweden)

    Sungwoo Lim

    Full Text Available Both homelessness and incarceration are associated with housing instability, which in turn can disrupt continuity of HIV medical care. Yet, their impacts have not been systematically assessed among people living with HIV/AIDS (PLWHA.We studied a retrospective cohort of 1,698 New York City PLWHA with both jail incarceration and homelessness during 2001-05 to evaluate whether frequent transitions between jail incarceration and homelessness were associated with a lower likelihood of continuity of HIV care during a subsequent one-year follow-up period. Using matched jail, single-adult homeless shelter, and HIV registry data, we performed sequence analysis to identify trajectories of these events and assessed their influence on engagement in HIV care and HIV viral suppression via marginal structural modeling.Sequence analysis identified four trajectories; 72% of the cohort had sporadic experiences of both brief incarceration and homelessness, whereas others experienced more consistent incarceration or homelessness during early or late months. Trajectories were not associated with differential engagement in HIV care during follow-up. However, compared with PLWHA experiencing early bouts of homelessness and later minimal incarceration/homelessness events, we observed a lower prevalence of viral suppression among PLWHA with two other trajectories: those with sporadic, brief occurrences of incarceration/homelessness (0.67, 95% CI = 0.50,0.90 and those with extensive incarceration experiences (0.62, 95% CI = 0.43,0.88.Housing instability due to frequent jail incarceration and homelessness or extensive incarceration may exert negative influences on viral suppression. Policies and services that support housing stability should be strengthened among incarcerated and sheltered PLWHA to reduce risk of adverse health conditions.

  9. Prolonged elevation of viral loads in HIV-1-infected children

    African Journals Online (AJOL)

    cqq1a

    2010-11-09

    Nov 9, 2010 ... treatment i.e. mean difference (signed-rank test) in viral load “before” and .... We used Abbott Determine and Unigold as the rapid HIV test kits. The ..... N: Number of patients, *: Wilcoxon signed ranks test for Median difference ...

  10. CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China.

    Science.gov (United States)

    Liu, Man-Qing; Tang, Li; Kong, Wen-Hua; Zhu, Ze-Rong; Peng, Jin-Song; Wang, Xia; Yao, Zhong-Zhao; Schilling, Robert; Zhou, Wang

    2013-10-01

    In China, the rate of human immunodeficiency virus (HIV) testing is increasing among men who have sex with men. The purpose of the present study was to describe HIV-related biomarkers and selected demographic variables of persons with newly diagnosed HIV/AIDS, among men who have sex with men in particular, in Wuhan China. Demographic indicators, and CD4+ T cell counts and HIV-1 viral load were collected from individuals newly identified as HIV-1 antibody positive during 2011. Of 176 enrolled patients, 132 (75.0%) were men who have sex with men. This group was significantly younger and had higher CD4+ T cell counts than patients who were likely infected through heterosexual contact. Most men who have sex with men (56.6%) were discovered by initiative investigation. Among heterosexual patients CD4+ T cell counts and HIV-1 viral load were significantly correlated; among the group of men who have sex with men, no such association was found. Copyright © 2013 Wiley Periodicals, Inc.

  11. Dataset of longitudinal analysis of tear cytokine levels, CD4, CD8 counts and HIV viral load in dry eye patients with HIV infection

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Balne

    2017-04-01

    Full Text Available The data presented in this article shows the longitudinal analysis of tear fluid cytokine profiles, blood CD4 and CD8 counts and HIV viral load in 34 dry eye patients with HIV infection during the HAART therapy. Clinical samples were collected from HIV patients with dry eye disease at the time of presentation to the clinic (visit 1, three months (visit 2 and 6 months (visit 3 after the presentation. At each time point tear samples were evaluated for 41 cytokines using Luminex bead based multiplex assay and blood samples were tested for HIV viral load and CD4 and CD8 counts.

  12. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

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    Petropoulos Christos J

    2005-11-01

    Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

  13. HIV taken by STORM: Super-resolution fluorescence microscopy of a viral infection

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    Pereira Cândida F

    2012-05-01

    Full Text Available Abstract Background The visualization of viral proteins has been hindered by the resolution limit of conventional fluorescent microscopes, as the dimension of any single fluorescent signal is often greater than most virion particles. Super-resolution microscopy has the potential to unveil the distribution of proteins at the resolution approaching electron microscopy without relying on morphological features of existing characteristics of the biological specimen that are needed in EM. Results Using direct stochastic optical reconstruction microscopy (dSTORM to achieve a lateral resolution of 15–20 nm, we quantified the 2-D molecular distribution of the major structural proteins of the infectious human immunodeficiency virus type 1 (HIV-1 before and after infection of lymphoid cells. We determined that the HIV-1 matrix and capsid proteins undergo restructuring soon after HIV-1 infection. Conclusions This study provides the proof-of-concept for the use of dSTORM to visualize the changes in the molecular distribution of viral proteins during an infection.

  14. Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

    Science.gov (United States)

    Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D

    2013-11-01

    To compare time to achieve viral load HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load HIV log10 viral load was associated with a later time of achieving viral load HIV log10 viral load was associated with a longer time of achieving viral load Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  15. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

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    Shoshana Y Kahana

    Full Text Available The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural and Esri Crime (e.g., global crime index databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1 being on antiretroviral therapy (ART currently; (2 being on ART for at least 6 months; (3 missed HIV care appointments (not having missed any vs. having missed one or more appointments over the past 12 months; and (4 viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability.Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%; ART use for ≥6 months (n = 861, 45.53%; at least one missed HIV care appointment (n = 936, 49.50; and viral suppression (n = 577, 30.51%. After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

  16. A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently.

    Science.gov (United States)

    Yamaguchi, Koushi; Sugiyama, Takahiro; Kato, Shinji; Kondo, Yoichi; Ageyama, Naohide; Kanekiyo, Masaru; Iwata, Misao; Koyanagi, Yoshio; Yamamoto, Naoki; Honda, Mitsuo

    2008-08-01

    In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIV(mac239) infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo.

  17. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

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    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  18. Field evaluation of an open and polyvalent universal HIV-1/SIVcpz/SIVgor quantitative RT-PCR assay for HIV-1 viral load monitoring in comparison to Abbott RealTime HIV-1 in Cameroon.

    Science.gov (United States)

    Guichet, Emilande; Aghokeng, Avelin; Eymard-Duvernay, Sabrina; Vidal, Nicole; Ayouba, Ahidjo; Mpoudi Ngole, Eitel; Delaporte, Eric; Ciaffi, Laura; Peeters, Martine

    2016-11-01

    With the increasing demand of HIV viral load (VL) tests in resource-limited countries (RLCs) there is a need for assays at affordable cost and able to quantify all known HIV-1 variants. VLs obtained with a recently developed open and polyvalent universal HIV-1/SIVcpz/SIVgor RT-qPCR were compared to Abbott RealTime HIV-1 assay in Cameroon. On 474 plasma samples, characterized by a wide range of VLs and a broad HIV-1 group M genetic diversity, 97.5% concordance was observed when using the lower detection limit of each assay. When using the threshold of 3.00 log 10 copies/mL, according to WHO guidelines to define virological failure (VF) in RLCs, the concordance was 94.7%, 360/474 versus 339/474 patients were identified with VF with the new assay and Abbott RealTime HIV-1, respectively. Higher VLs were measured with the new assay, +0.47 log 10 copies/mL (95% CI; 0.42-0.52) as shown with Bland-Altman analysis. Eleven samples from patients on VF with drug resistance were not detected by Abbott RealTime HIV-1 versus two only with the new assay. Overall, our study showed that the new assay can be easily implemented in a laboratory in RLCs with VL experience and showed good performance on a wide diversity of HIV-1 group M variants. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Association of HIV diversity and survival in HIV-infected Ugandan infants.

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    Maria M James

    2011-04-01

    Full Text Available The level of viral diversity in an HIV-infected individual can change during the course of HIV infection, reflecting mutagenesis during viral replication and selection of viral variants by immune and other selective pressures. Differences in the level of viral diversity in HIV-infected infants may reflect differences in viral dynamics, immune responses, or other factors that may also influence HIV disease progression. We used a novel high resolution melting (HRM assay to measure HIV diversity in Ugandan infants and examined the relationship between diversity and survival through 5 years of age.Plasma samples were obtained from 31 HIV-infected infants (HIVNET 012 trial. The HRM assay was used to measure diversity in two regions in the gag gene (Gag1 and Gag2 and one region in the pol gene (Pol.HRM scores in all three regions increased with age from 6-8 weeks to 12-18 months (for Gag1: P = 0.005; for Gag2: P = 0.006; for Pol: P = 0.016. Higher HRM scores at 6-8 weeks of age (scores above the 75(th percentile were associated with an increased risk of death by 5 years of age (for Pol: P = 0.005; for Gag1/Gag2 (mean of two scores: P = 0.003; for Gag1/Gag2/Pol (mean of three scores: P = 0.002. We did not find an association between HRM scores and other clinical and laboratory variables.Genetic diversity in HIV gag and pol measured using the HRM assay was typically low near birth and increased over time. Higher HIV diversity in these regions at 6-8 weeks of age was associated with a significantly increased risk of death by 5 years of age.

  20. Association between feline immunodeficiency virus (FIV) plasma viral RNA load, concentration of acute phase proteins and disease severity.

    Science.gov (United States)

    Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne

    2014-08-01

    Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

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    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  2. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. Methods: WLWH between 18...

  3. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    José E. Levi

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  4. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Levi José E.

    2002-01-01

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  5. Pooled HIV-1 viral load testing using dried blood spots to reduce the cost of monitoring antiretroviral treatment in a resource-limited setting.

    Science.gov (United States)

    Pannus, Pieter; Fajardo, Emmanuel; Metcalf, Carol; Coulborn, Rebecca M; Durán, Laura T; Bygrave, Helen; Ellman, Tom; Garone, Daniela; Murowa, Michael; Mwenda, Reuben; Reid, Tony; Preiser, Wolfgang

    2013-10-01

    Rollout of routine HIV-1 viral load monitoring is hampered by high costs and logistical difficulties associated with sample collection and transport. New strategies are needed to overcome these constraints. Dried blood spots from finger pricks have been shown to be more practical than the use of plasma specimens, and pooling strategies using plasma specimens have been demonstrated to be an efficient method to reduce costs. This study found that combination of finger-prick dried blood spots and a pooling strategy is a feasible and efficient option to reduce costs, while maintaining accuracy in the context of a district hospital in Malawi.

  6. Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

    Science.gov (United States)

    Spencer, LaShonda Y; Christiansen, Shawna; Wang, Chia-Hao H; Mack, Wendy J; Young, Mary; Strickler, Howard D; Anastos, Kathryn; Minkoff, Howard; Cohen, Mardge; Geenblatt, Ruth M; Karim, Roksana; Operskalski, Eva; Frederick, Toni; Homans, James D; Landay, Alan; Kovacs, Andrea

    2016-02-01

    Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV

  7. Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control.

    Science.gov (United States)

    Ruiz-Riol, M; Berdnik, D; Llano, A; Mothe, B; Gálvez, C; Pérez-Álvarez, S; Oriol-Tordera, B; Olvera, A; Silva-Arrieta, S; Meulbroek, M; Pujol, F; Coll, J; Martinez-Picado, J; Ganoza, C; Sanchez, J; Gómez, G; Wyss-Coray, T; Brander, C

    2017-08-15

    Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia ( P HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/β-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor ( IL27RA ) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and

  8. A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

    Science.gov (United States)

    Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-07-01

    Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log 10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log 10 cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log 10 cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy.

    Science.gov (United States)

    Wang, Nidan; Li, Yijia; Han, Yang; Xie, Jing; Li, Taisheng

    2017-06-01

    The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Health information technology interventions enhance care completion, engagement in HIV care and treatment, and viral suppression among HIV-infected patients in publicly funded settings.

    Science.gov (United States)

    Shade, Starley B; Steward, Wayne T; Koester, Kimberly A; Chakravarty, Deepalika; Myers, Janet J

    2015-04-01

    The National HIV/AIDS Strategy (NHAS) emphasizes the use of technology to facilitate coordination of comprehensive care for people with HIV. We examined the effect of six health information technology (HIT) interventions in a Ryan White-funded Special Projects of National Significance (SPNS) on care completion services, engagement in HIV care, and viral suppression. Interventions included use of surveillance data to identify out-of-care individuals, extending access to electronic health records to support service providers, use of electronic laboratory ordering and prescribing, and development of a patient portal. Data from a sample of electronic patient records from each site were analyzed to assess changes in utilization of comprehensive care (prevention screening, support service utilization), engagement in primary HIV medical care (receipt of services and use of antiretroviral therapy), and viral suppression. We used weighted generalized estimating equations to estimate outcomes while accounting for the unequal contribution of data and differences in the distribution of patient characteristics across sites and over time. We observed statistically significant changes in the desired direction in comprehensive care utilization and engagement in primary care outcomes targeted by each site. Five of six sites experienced statistically significant increases in viral suppression. These results provide additional support for the use of HIT as a valuable tool for achieving the NHAS goal of providing comprehensive care for all people living with HIV. HIT has the potential to increase utilization of services, improve health outcomes for people with HIV, and reduce community viral load and subsequent transmission of HIV. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com For affiliation see end of article.

  11. Impact of Chloroquine on Viral Load in Breast Milk

    Science.gov (United States)

    Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

    2006-01-01

    Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

  12. Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.

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    Michael J Dapp

    Full Text Available Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS participants who had not received combination antiretroviral therapy (ART. This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017, and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.

  13. A Robust PCR Protocol for HIV Drug Resistance Testing on Low-Level Viremia Samples

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    Shivani Gupta

    2017-01-01

    Full Text Available The prevalence of drug resistance (DR mutations in people with HIV-1 infection, particularly those with low-level viremia (LLV, supports the need to improve the sensitivity of amplification methods for HIV DR genotyping in order to optimize antiretroviral regimen and facilitate HIV-1 DR surveillance and relevant research. Here we report on a fully validated PCR-based protocol that achieves consistent amplification of the protease (PR and reverse transcriptase (RT regions of HIV-1 pol gene across many HIV-1 subtypes from LLV plasma samples. HIV-spiked plasma samples from the External Quality Assurance Program Oversight Laboratory (EQAPOL, covering various HIV-1 subtypes, as well as clinical specimens were used to optimize and validate the protocol. Our results demonstrate that this protocol has a broad HIV-1 subtype coverage and viral load span with high sensitivity and reproducibility. Moreover, the protocol is robust even when plasma sample volumes are limited, the HIV viral load is unknown, and/or the HIV subtype is undetermined. Thus, the protocol is applicable for the initial amplification of the HIV-1 PR and RT genes required for subsequent genotypic DR assays.

  14. Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults.

    Science.gov (United States)

    Thames, April D; Kuhn, Taylor P; Williamson, Timothy J; Jones, Jacob D; Mahmood, Zanjbeel; Hammond, Andrea

    2017-01-01

    The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

    2013-09-23

    We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The Alphabet Soup of HIV Reservoir Markers.

    Science.gov (United States)

    Sharaf, Radwa R; Li, Jonathan Z

    2017-04-01

    Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir. In this review, we assess the most commonly used HIV reservoir assays, as a clear understanding of the strengths and weaknesses of each is vital for the accurate interpretation of results and for the development of improved assays. The quantification of intracellular or plasma HIV RNA or DNA levels remains the most commonly used tests for the characterization of the viral reservoir. While cost-effective and high-throughput, these assays are not able to differentiate between replication-competent or defective fractions or quantify the number of infected cells. Viral outgrowth assays provide a lower bound for the fraction of cells that can produce infectious virus, but these assays are laborious, expensive and substantially underestimate the potential reservoir of replication-competent provirus. Newer assays are now available that seek to overcome some of these problems, including full-length proviral sequencing, inducible HIV RNA assays, ultrasensitive p24 assays and murine adoptive transfer techniques. The development and evaluation of strategies for HIV remission rely upon our ability to accurately and precisely quantify the size of the remaining viral reservoir. At this time, all current HIV reservoir assays have drawbacks such that combinations of assays are generally needed to gain a more comprehensive view of the viral reservoir. The development of novel, rapid, high-throughput assays that can sensitively quantify the levels of the replication-competent HIV reservoir is still needed.

  17. Extracellular histones identified in crocodile blood inhibit in-vitro HIV-1 infection.

    Science.gov (United States)

    Kozlowski, Hannah N; Lai, Eric T L; Havugimana, Pierre C; White, Carl; Emili, Andrew; Sakac, Darinka; Binnington, Beth; Neschadim, Anton; McCarthy, Stephen D S; Branch, Donald R

    2016-08-24

    It has been reported that crocodile blood contains potent antibacterial and antiviral properties. However, its effects on HIV-1 infection remain unknown. We obtained blood from saltwater crocodiles to examine whether serum or plasma could inhibit HIV-1 infection. We purified plasma fractions then used liquid chromatography-mass spectrometry to identify the inhibitory protein factor(s). We then analyzed the ability of recombinant proteins to recapitulate HIV-1 inhibition and determine their mechanism of action. Crocodylus porosus plasma was tested for inhibition of Jurkat T-cell HIV-1 infection. Inhibitor(s) were purified by reverse-phase chromatography then identified by protein liquid chromatography-mass spectrometry. Anti-HIV-1 activity of purified plasma or recombinant proteins were measured by p24 enzyme-linked immunosorbent assay and luciferase readouts, and mechanism of action was determined by measuring HIV-1 RNA, cDNA and transcription (using 1G5 cells). Crocodile plasma contains potent inhibitors of HIV-1IIIB infection, which were identified as histones. Recombinant human histones H1 and H2A significantly reduced HIV-1JR-FL infection (IC50 of 0.79 and 0.45 μmol/l, respectively), whereas H4 enhanced JR-FL luciferase activity. The inhibitory effects of crocodile plasma, recombinant H1 or recombinant H2A on HIV-1 infection were during or post-viral transcription. Circulating histones in crocodile blood, possibly released by neutrophil extracellular traps, are significant inhibitors of HIV-1 infection in-vitro. Extracellular recombinant histones have different effects on HIV-1 transcription and protein expression and are downregulated in HIV-1 patients. Circulating histones may be a novel resistance factor during HIV-1 infection, and peptide versions should be explored as future HIV-1 therapeutics that modulate viral transcription.

  18. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

    DEFF Research Database (Denmark)

    Obel, Niels

    2016-01-01

    OBJECTIVES: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. DESIGN: Collaborative analysis of data from eight European and three Canadian cohorts. METHODS: Adults (N>20 000) who started triple ART between 199...

  19. Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections

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    Enrique Fuentes-Mattei

    2017-06-01

    Full Text Available Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8 varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR, and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV, a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1 IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P < 0.001. The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the “gold” standard method to detect certain viral infections in clinical practice.

  20. Viral hepatitis and HIV-associated tuberculosis: Risk factors and TB treatment outcomes in Thailand

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    Likanonsakul Sirirat

    2008-07-01

    Full Text Available Abstract Background The occurrence of tuberculosis (TB, human immunodeficiency virus (HIV, and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. Methods Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST, alanine aminotransferase (ALT, total bilirubin (BR, complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. Results Of 769 enrolled patients, 752 (98% had serologic testing performed for viral hepatitis: 70 (9% were reactive for HBsAg, 237 (31% for anti-HCV, and 472 (63% non-reactive for both markers. At the beginning of TB treatment, 18 (26% patients with HBsAg reactivity had elevated liver function tests compared with 69 (15% patients non-reactive to any viral marker (p = 0.02. At the end of TB treatment, 493 (64% were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3 and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0. Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2 and living in Bangkok (AOR, 15.8; CI, 9.4–26.5. The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. Conclusion Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus

  1. Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA

    DEFF Research Database (Denmark)

    Jakobsen, Martin Roelsgaard; Tolstrup, M; Bertelsen, L

    2007-01-01

    on real-time PCR and amplification refractory mutation system (ARMS). RESULTS: The 103N and 184V mutations were not detected in patients with stable low viremia. Patients previously exposed to mono or dual therapy often carried minor viral populations of either one or both mutations in plasma. The viral......BACKGROUND: Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment. OBJECTIVE: To develop an ARMS assay for plasma virions...... an unequal distribution of linked-mutation populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V mutation may be more fit than the single 184V mutation and this linked population emerges rapidly under inadequate drug pressure. Udgivelsesdato: 2007-Jul...

  2. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages

    International Nuclear Information System (INIS)

    Jiang Jiyang; Aiken, Christopher

    2006-01-01

    HIV-1 infection requires fusion of viral and cellular membranes in a reaction catalyzed by the viral envelope proteins gp120 and gp41. We recently reported that efficient HIV-1 particle fusion with target cells is linked to maturation of the viral core by an activity of the gp41 cytoplasmic domain. Here, we show that maturation enhances the fusion of a variety of recombinant viruses bearing primary and laboratory-adapted Env proteins with primary human CD4 + T cells. Overall, HIV-1 fusion was more dependent on maturation for viruses bearing X4-tropic envelope proteins than for R5-tropic viruses. Fusion of HIV-1 with monocyte-derived macrophages was also dependent on particle maturation. We conclude that the ability to couple fusion to particle maturation is a common feature of HIV-1 Env proteins and may play an important role during HIV-1 replication in vivo

  3. The semen microbiome and its relationship with local immunology and viral load in HIV infection.

    Directory of Open Access Journals (Sweden)

    Cindy M Liu

    2014-07-01

    Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2  = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

  4. Fluorescent protein-tagged Vpr dissociates from HIV-1 core after viral fusion and rapidly enters the cell nucleus.

    Science.gov (United States)

    Desai, Tanay M; Marin, Mariana; Sood, Chetan; Shi, Jiong; Nawaz, Fatima; Aiken, Christopher; Melikyan, Gregory B

    2015-10-29

    HIV-1 Vpr is recruited into virions during assembly and appears to remain associated with the viral core after the reverse transcription and uncoating steps of entry. This feature has prompted the use of fluorescently labeled Vpr to visualize viral particles and to follow trafficking of post-fusion HIV-1 cores in the cytoplasm. Here, we tracked single pseudovirus entry and fusion and observed that fluorescently tagged Vpr gradually dissociates from post-fusion viral cores over the course of several minutes and accumulates in the nucleus. Kinetics measurements showed that fluorescent Vpr released from the cores very rapidly entered the cell nucleus. More than 10,000 Vpr molecules can be delivered into the cell nucleus within 45 min of infection by HIV-1 particles pseudotyped with the avian sarcoma and leukosis virus envelope glycoprotein. The fraction of Vpr from cell-bound viruses that accumulated in the nucleus was proportional to the extent of virus-cell fusion and was fully blocked by viral fusion inhibitors. Entry of virus-derived Vpr into the nucleus occurred independently of envelope glycoproteins or target cells. Fluorescence correlation spectroscopy revealed two forms of nuclear Vpr-monomers and very large complexes, likely involving host factors. The kinetics of viral Vpr entering the nucleus after fusion was not affected by point mutations in the capsid protein that alter the stability of the viral core. The independence of Vpr shedding of capsid stability and its relatively rapid dissociation from post-fusion cores suggest that this process may precede capsid uncoating, which appears to occur on a slower time scale. Our results thus demonstrate that a bulk of fluorescently labeled Vpr incorporated into HIV-1 particles is released shortly after fusion. Future studies will address the question whether the quick and efficient nuclear delivery of Vpr derived from incoming viruses can regulate subsequent steps of HIV-1 infection.

  5. Redefining the Viral Reservoirs That Prevent HIV-1 Eradication

    Science.gov (United States)

    Eisele, Evelyn; Siliciano, Robert F.

    2014-01-01

    Summary This review proposes definitions for key terms in the field of HIV-1 latency and eradication. In the context of eradication, a reservoir is a cell type that allows persistence of replication-competent HIV-1 on a time scale of years in patients on optimal antiretroviral therapy. Reservoirs act as a barrier to eradication in the patient population in whom cure attempts will likely be made. Halting viral replication is essential to eradication, and definitions and criteria for assessing whether this goal has been achieved are proposed. The cell types that may serve as reservoirs for HIV-1 are discussed. Currently, only latently infected resting CD4+ T cells fit the proposed definition of a reservoir, and more evidence is necessary to demonstrate that other cell types including hematopoietic stem cells and macrophages fit this definition. Further research is urgently required on potential reservoirs in the gut-associated lymphoid tissue and the central nervous system. PMID:22999944

  6. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Directory of Open Access Journals (Sweden)

    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  7. Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.

    Science.gov (United States)

    Gibellini, Lara; Pecorini, Simone; De Biasi, Sara; Pinti, Marcello; Bianchini, Elena; De Gaetano, Anna; Digaetano, Margherita; Pullano, Rosalberta; Lo Tartaro, Domenico; Iannone, Anna; Mussini, Cristina; Cossarizza, Andrea; Nasi, Milena

    2018-02-01

    Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection

    Science.gov (United States)

    Liu, Cindy M.; Osborne, Brendan J. W.; Hungate, Bruce A.; Shahabi, Kamnoosh; Huibner, Sanja; Lester, Richard; Dwan, Michael G.; Kovacs, Colin; Contente-Cuomo, Tania L.; Benko, Erika; Aziz, Maliha

    2014-01-01

    Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission. PMID:25058515

  9. Prevalence of HIV infection among former commercial plasma donors in rural eastern China.

    Science.gov (United States)

    Wu, Z; Rou, K; Detels, R

    2001-03-01

    Sporadic reports of HIV-1 infection among commercial plasma donors in China between 1994 and 1995. (1) To determine the prevalence of HIV infection among repeat plasma donors; (2) to identify factors associated with HIV infection; and (3) to describe characteristics associated with secondary transmission. Plasma/blood donors who had a history of donating plasma/blood before March 1, 1995, their spouses, and their children under 5 years were recruited for a cross-sectional study. A questionnaire and an HIV test were collected anonymously. Information collected included demographic characteristics, sexual behaviour, recreational drug use and history of medical care and blood/plasma donation. HIV antibody was identified by the Hema-Strip rapid test and confirmed by Western blot. The prevalence of HIV infection was calculated and risk factors associated with infection determined by univariate analyses followed by multivariate modelling. A total of 1517 individuals were interviewed and tested, of whom 1043 adults admitted to donating plasma. The prevalence of HIV infection among plasma donors was 12.5% and among their non-donor spouses was 2.1%. Prevalence was inversely related to educational level and was higher in married participants, but was not associated with medical care, drug abuse or multiple sexual partners. A higher frequency of plasma donation was directly associated with a higher risk of HIV infection. Multivariate analyses demonstrated that being HIV-positive was associated with being 30 to 49 years old [odds ratio (OR) = 1.9], donating both plasma and blood (OR = 2.5), and the frequency of plasma donation (OR = 14 for >10 donations per month). The study demonstrated that the prevalence of HIV infection in the commercial plasma donor population was alarmingly high. Many married individuals and those getting married in the future will transmit the virus to their spouses and future children. Plasma donors need to be alerted to the risk of being infected with

  10. The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.

    Science.gov (United States)

    Nolan, David J; Rose, Rebecca; Rodriguez, Patricia H; Salemi, Marco; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S

    2018-01-01

    Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

  11. Avances recientes en HIV/SIDA: Patogénesis, historia natural y carga viral

    Directory of Open Access Journals (Sweden)

    Rafael E Campo

    1996-10-01

    Full Text Available Results of recent investigations have given us a new understanding of the pathogenesis of HIV infection. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication is the principal force driving the destruction of CD4 lymphocytes. This knowledge will lead us to design better treatment strategies directed to curtail viral replication and prevent the emergence of viral resistance, and the use of combination antiretroviral therapy is a first example of these new strategies. The concept of viral load is introduced, and we discuss the usefulness of viral load in the clinical prognosis of this disease, and its use as an aid in the decision-making process when starling or mordifyng antiretroviral therapy in our patients. (Rev Med Hered 1996; 7: 182-188.

  12. The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection

    Science.gov (United States)

    Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre

    2016-01-01

    Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377

  13. Higher retention and viral suppression with adolescent-focused HIV clinic in South Africa.

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    Brian C Zanoni

    Full Text Available To determine retention in care and virologic suppression among HIV-infected adolescents and young adults attending an adolescent-friendly clinic compared to those attending the standard pediatric clinic at the same site.Retrospective cohort analysis.Government supported, hospital-based antiretroviral clinic in KwaZulu-Natal, South Africa.Two hundred forty-one perinatally HIV-infected adolescents and young adults aged 13 to 24 years attending an adolescent-friendly clinic or the standard pediatric clinic from April 2007 to November 2015.Attendance in an adolescent-friendly clinic compared to a standard pediatric clinic.Retention in care defined as one clinic visit or pharmacy refill in the prior 6 months; HIV-1 viral suppression defined as < 400 copies/ml.Overall, among 241 adolescents and young adults, retention was 89% (214/241 and viral suppression was 81% (196/241. Retention was higher among those attending adolescent clinic (95% versus standard pediatric clinic (85%; OR 3.7; 95% confidence interval (CI 1.2-11.1; p = 0.018. Multivariable logistic regression adjusted for age at ART initiation, gender, pre-ART CD4 count, months on ART, and tuberculosis history indicated higher odds of retention in adolescents and young adults attending adolescent compared to standard clinic (AOR = 8.5; 95% CI 2.3-32.4; p = 0.002. Viral suppression was higher among adolescents and young adults attending adolescent (91% versus standard pediatric clinic (80%; OR 2.5; 95% CI 1.1-5.8; p = 0.028. A similar multivariable logistic regression model indicated higher odds of viral suppression in adolescents and young adults attending adolescent versus standard pediatric clinic (AOR = 3.8; 95% CI 1.5-9.7; p = 0.005.Adolescents and young adults attending an adolescent-friendly clinic had higher retention in care and viral suppression compared to adolescents attending the standard pediatric clinic. Further studies are needed to prospectively assess the impact of adolescent

  14. Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations.

    Science.gov (United States)

    Bull, Marta; Learn, Gerald; Genowati, Indira; McKernan, Jennifer; Hitti, Jane; Lockhart, David; Tapia, Kenneth; Holte, Sarah; Dragavon, Joan; Coombs, Robert; Mullins, James; Frenkel, Lisa

    2009-09-22

    Compartmentalization of HIV-1 between the genital tract and blood was noted in half of 57 women included in 12 studies primarily using cell-free virus. To further understand differences between genital tract and blood viruses of women with chronic HIV-1 infection cell-free and cell-associated virus populations were sequenced from these tissues, reasoning that integrated viral DNA includes variants archived from earlier in infection, and provides a greater array of genotypes for comparisons. Multiple sequences from single-genome-amplification of HIV-1 RNA and DNA from the genital tract and blood of each woman were compared in a cross-sectional study. Maximum likelihood phylogenies were evaluated for evidence of compartmentalization using four statistical tests. Genital tract and blood HIV-1 appears compartmentalized in 7/13 women by >/=2 statistical analyses. These subjects' phylograms were characterized by low diversity genital-specific viral clades interspersed between clades containing both genital and blood sequences. Many of the genital-specific clades contained monotypic HIV-1 sequences. In 2/7 women, HIV-1 populations were significantly compartmentalized across all four statistical tests; both had low diversity genital tract-only clades. Collapsing monotypic variants into a single sequence diminished the prevalence and extent of compartmentalization. Viral sequences did not demonstrate tissue-specific signature amino acid residues, differential immune selection, or co-receptor usage. In women with chronic HIV-1 infection multiple identical sequences suggest proliferation of HIV-1-infected cells, and low diversity tissue-specific phylogenetic clades are consistent with bursts of viral replication. These monotypic and tissue-specific viruses provide statistical support for compartmentalization of HIV-1 between the female genital tract and blood. However, the intermingling of these clades with clades comprised of both genital and blood sequences and the absence

  15. Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements

    NARCIS (Netherlands)

    Lanoy, Emilie; May, Margaret; Mocroft, Amanda; Phillips, Andrew; Justice, Amy; Chene, Genevieve; Furrer, Hansjakob; Sterling, Timothy; D'Arminio Monforte, Antonella; Force, Lluis; Gill, John; Harris, Ross; Hogg, Robert S.; Rockstroh, Juergen; Saag, Mike; Khaykin, Pavel; de Wolf, Frank; Sterne, Jonathan A. C.; Costagliola, Dominique

    2009-01-01

    Objectives: CD4 cell count and plasma viral load are well known predictors of AIDS and mortality in HIV-1-infected patients treated with combination antiretroviral therapy (cART). This study investigated, in patients treated for at least 3 years, the respective prognostic importance of values

  16. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay.

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    Gregory M Laird

    Full Text Available HIV-1 persists in infected individuals in a stable pool of resting CD4(+ T cells as a latent but replication-competent provirus. This latent reservoir is the major barrier to the eradication of HIV-1. Clinical trials are currently underway investigating the effects of latency-disrupting compounds on the persistence of the latent reservoir in infected individuals. To accurately assess the effects of such compounds, accurate assays to measure the frequency of latently infected cells are essential. The development of a simpler assay for the latent reservoir has been identified as a major AIDS research priority. We report here the development and validation of a rapid viral outgrowth assay that quantifies the frequency of cells that can release replication-competent virus following cellular activation. This new assay utilizes bead and column-based purification of resting CD4(+ T cells from the peripheral blood of HIV-1 infected patients rather than cell sorting to obtain comparable resting CD4(+ T cell purity. This new assay also utilizes the MOLT-4/CCR5 cell line for viral expansion, producing statistically comparable measurements of the frequency of latent HIV-1 infection. Finally, this new assay employs a novel quantitative RT-PCR specific for polyadenylated HIV-1 RNA for virus detection, which we demonstrate is a more sensitive and cost-effective method to detect HIV-1 replication than expensive commercial ELISA detection methods. The reductions in both labor and cost make this assay suitable for quantifying the frequency of latently infected cells in clinical trials of HIV-1 eradication strategies.

  17. Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

    Science.gov (United States)

    Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

    2018-02-21

    The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

  18. Disseminated HIV-Associated Kaposi’s Sarcoma With High CD4 Cell Count And Low Viral Load

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    Diana Pereira Anjos

    2017-12-01

    Full Text Available Kaposi’s sarcoma is considered an acquired immunodeficiency syndrome-defining illness and is caused by human herpesvirus 8. It has been associated with patients infected with human immunodeficiency virus (HIV who have CD4 T lymphocytes <200 cells/uL and high viral loads. We report a case of a 23-year old woman infected with HIV-1 and receiving antiretroviral treatment since diagnosis, with high CD4 cell count and low viral load that presented with disseminated Kaposi’s sarcoma. Clinicians should be aware of the occurrence of Kaposi’s sarcoma despite robust CD4 cell counts.

  19. High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

    Science.gov (United States)

    Farquhar, Carey; Nduati, Ruth; Haigwood, Nancy; Sutton, William; Mbori-Ngacha, Dorothy; Richardson, Barbra; John-Stewart, Grace

    2012-01-01

    Background Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. Methods To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Results Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). Conclusions This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants. PMID:16280707

  20. Computerized counseling reduces HIV-1 viral load and sexual transmission risk: findings from a randomized controlled trial.

    Science.gov (United States)

    Kurth, Ann E; Spielberg, Freya; Cleland, Charles M; Lambdin, Barrot; Bangsberg, David R; Frick, Pamela A; Severynen, Anneleen O; Clausen, Marc; Norman, Robert G; Lockhart, David; Simoni, Jane M; Holmes, King K

    2014-04-15

    Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Longitudinal randomized controlled trial. An academic HIV clinic and a community-based organization in Seattle. In a total of 240 HIV-positive adults on ART, 209 completed 9-month follow-up (87% retention). Randomization to computerized counseling or assessment only, 4 sessions over 9 months. HIV-1 viral suppression, and self-reported ART adherence and transmission risks, compared using generalized estimating equations. Overall, intervention participants had reduced viral load: mean 0.17 log10 decline, versus 0.13 increase in controls, P = 0.053, and significant difference in ART adherence baseline to 9 months (P = 0.046). Their sexual transmission risk behaviors decreased (odds ratio = 0.55, P = 0.020), a reduction not seen among controls (odds ratio = 1.1, P = 0.664), and a significant difference in change (P = 0.040). Intervention effect was driven by those most in need; among those with detectable virus at baseline (>30 copies/mL, n = 89), intervention effect was mean 0.60 log10 viral load decline versus 0.15 increase in controls, P = 0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, P = 0.038. Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior.

  1. Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Raquel Autran Coelho

    2004-03-01

    Full Text Available OBJETIVVO: relacionar a gravidade de lesão cervical diagnosticada por exame citopatológico à contagem de células CD4+ e à carga viral de RNA-HIV em pacientes HIV-soropositivas. MÉTODOS: foram avaliadas retrospectivamente, por meio de revisão de prontuários, 115 pacientes HIV-positivas atendidas em ambulatório de hospital universitário, no período de janeiro de 2002 até abril de 2003. Oitenta e três casos apresentaram diagnóstico de neoplasia intra-epitelial cervical (NIC ao exame citopatológico, e trinta e dois, exames sem alterações. Todas as pacientes apresentavam contagem de células CD4+ e carga viral à época do exame. Os casos foram distribuídos quanto ao índice de células CD4+ em três grupos: CD4 acima de 500 cel/mm³, entre 200 e 500 cel/mm³ ou abaixo de 200 cel/mm³, e, em outros três grupos, quanto à carga viral de HIV: menor do que 10.000 cópias RNA-HIV/mL, entre 10.000 e 100.000 cópias RNA-HIV/mL ou maior do que 100.000 cópias RNA-HIV/mL. A verificação da hipótese de associação foi realizada por meio do teste exato de Fisher. RESULTADOS: das 83 pacientes com NIC citopatológico, 73% apresentaram contagem de células CD4+ abaixo de 500 células/mm³. Em qualquer das faixas de contagem de células CD4+, mais da metade das pacientes apresentavam NIC I citopatológico. Quanto à carga viral de HIV, 71,7% das pacientes com menor carga viral de HIV apresentaram NIC I, ao passo que 11,3% revelaram NIC III. Já no grupo com maior carga viral (100.000 cópias/mL, em 61,5% do total de pacientes o exame citopatológico foi compatível com NIC I, e 30,8% com NIC III. CONCLUSÃO: houve evidência de associação entre carga viral e NIC (p=0.013, não sendo observado o mesmo em relação à contagem de linfócitos CD4+. A presença de infecção secundária cervicovaginal foi considerada possível fator confundidor.PURPOSE: to correlate the type of cervical lesion diagnosed by Pap smear with CD4 cell counts and HIV

  2. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  3. Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.

    Science.gov (United States)

    Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W

    2016-08-01

    We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  4. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

    DEFF Research Database (Denmark)

    Chereau, Fanny; Madec, Yoann; Sabin, Caroline

    2017-01-01

    OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. MET...

  5. Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 ...

    African Journals Online (AJOL)

    Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected untreated children in Kenya; implication for immunodeficiency and AIDS progression. Washingtone Ochieng, Dorington Ogoyi, Francis J Mulaa, Simon Ogola, Rachel Musoke, Moses G Otsyula ...

  6. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  7. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

    Science.gov (United States)

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-01-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

  8. Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA

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    Soros Vanessa

    2008-10-01

    Full Text Available Abstract HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68ΔC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68ΔC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68ΔC. We demonstrate that inhibition of HIV expression by Sam68ΔC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68ΔC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.

  9. Multivariate analysis of covariates of adherence among HIV-positive mothers with low viral suppression.

    Science.gov (United States)

    Nsubuga-Nyombi, Tamara; Sensalire, Simon; Karamagi, Esther; Aloyo, Judith; Byabagambi, John; Rahimzai, Mirwais; Nabitaka, Linda Kisaakye; Calnan, Jacqueline

    2018-03-31

    As part of efforts to improve the prevention of mother-to-child transmission in Northern Uganda, we explored reasons for poor viral suppression among 122 pregnant and lactating women who were in care, received viral load tests, but had not achieved viral suppression and had more than 1000 copies/mL. Understanding the patient factors associated with low viral suppression was of interest to the Ministry of Health to guide the development of tools and interventions to achieve viral suppression for pregnant and lactating women newly initiating on ART as well as those on ART with unsuppressed viral load. A facility-based cross-sectional and mixed methods study design was used, with retrospective medical record review. We assessed 122 HIV-positive mothers with known low viral suppression across 31 health facilities in Northern Uganda. Adjusted odds ratios were used to determine the covariates of adherence among HIV positive mothers using logistic regression. A study among health care providers shed further light on predictors of low viral suppression and a history of low early retention. This study was part of a larger national evaluation of the performance of integrated care services for mothers. Adherence defined as taking antiretroviral medications correctly everyday was low at 67.2%. The covariates of low adherence are: taking other medications in addition to ART, missed appointments in the past 6 months, experienced violence in the past 6 months, and faces obstacles to treatment. Mothers who were experiencing each of these covariates were less likely to adhere to treatment. These covariates were triangulated with perspectives of health providers as covariates of low adherence and included: long distances to health facility, missed appointments, running out of pills, sharing antiretroviral drugs, violence, and social lifestyles such as multiple sexual partners coupled with non-disclosure to partners. Inadequate counseling, stigma, and lack of client identity are

  10. Individual and community factors associated with geographic clusters of poor HIV care retention and poor viral suppression.

    Science.gov (United States)

    Eberhart, Michael G; Yehia, Baligh R; Hillier, Amy; Voytek, Chelsea D; Fiore, Danielle J; Blank, Michael; Frank, Ian; Metzger, David S; Brady, Kathleen A

    2015-05-01

    Previous analyses identified specific geographic areas in Philadelphia (hotspots) associated with negative outcomes along the HIV care continuum. We examined individual and community factors associated with residing in these hotspots. Retrospective cohort of 1404 persons newly diagnosed with HIV in 2008-2009 followed for 24 months after linkage to care. Multivariable regression examined associations between individual (age, sex, race/ethnicity, HIV transmission risk, and insurance status) and community (economic deprivation, distance to care, access to public transit, and access to pharmacy services) factors and the outcomes: residence in a hotspot associated with poor retention-in-care and residence in a hotspot associated with poor viral suppression. In total, 24.4% and 13.7% of persons resided in hotspots associated with poor retention and poor viral suppression, respectively. For persons residing in poor retention hotspots, 28.3% were retained in care compared with 40.4% of those residing outside hotspots (P care, and longer distance to pharmacies. Factors significantly associated with residence in poor viral suppression hotspots included female sex, higher economic deprivation, and shorter distance to pharmacies. Individual and community-level associations with geographic hotspots may inform both content and delivery strategies for interventions designed to improve retention-in-care and viral suppression.

  11. Comparación de los métodos de cuantificación de carga viral de VIH: COBAS® AmpliPrep/COBAS® TaqMan HIV-1 test, v 2.0, y VERSANT HIV-1 RNA 1.0 Assay (kPCR Comparison of COBAS® AmpliPrep/COBAS® TaqMan HIV-1 test, v 2.0 and VERSANT HIV-1 RNA 1.0 (kPCR assays for HIV-1 plasma viral load

    Directory of Open Access Journals (Sweden)

    María Isabel Múnera-Jaramillo

    2012-03-01

    Full Text Available Objetivo. El propósito del estudio fue evaluar el desempeño del método VERSANTHIV-1RNA 1.0 Assay® (kPCR (Siemens, para la cuantificación de la carga viral en pacientes con VIH-1, en comparación con el método COBAS® AmpliPrep/COBAS TaqMan HIV-1 test®, v2.0 (Roche Diagnostics (CAP/CTM. Métodos. Las muestras fueron tomadas en dos tubos con EDTA, de 60 pacientes remitidos por el médico tratante para pruebas de carga viral como parte de su control de rutina de VIH/sida, y fueron procesadas para la cuantificación del ARN del VIH-1 por ambas técnicas. Se hizo análisis de regresión y se calcularon los coeficientes de correlación de Pearson, y los de correlación y concordancia de Lin. Se evalúo la concordancia entre las dos técnicas mediante el método de Bland-Altman. Resultados. El promedio de la carga viral por el método CAP/CTM fue 3,2±1,4 long10 copias/ml y, por el método kPCR, 3,0±1,3 long10 copias/ml. El 86,7 % de muestras presentó diferencias entre los dos métodos, menores de 0,5 long10 copias/ml, y el 13,3 % presentó diferencias mayores. El coeficiente de correlación de Pearson entre los dos métodos fue de 0,97 (IC95% 0,95-0,99 y el índice kappa ponderado entre los dos métodos en diferentes rangos de concentración, fue de 0,91 (IC95% 0,87-0,96. El promedio de las diferencias entre las mediciones fue 0,22 long10 copias/ml (IC95% -0,45 a 0,89. Conclusión. Las dos técnicas evaluadas fueron comparables, con el método kPCR se observaron resultados más bajos.Objective: The purpose of this study was to evaluate the performance of the kPCR VERSANT (™ 440 HIV-1RNA 3.0 Assay® (Siemens method for the quantification of viral load in HIV-1 patients, compared to the COBAS AmpliPrep/COBASTaqMan HIV-1 test®, v. 2.0 (Roche Diagnostics (CAP/CTM. Methods: Samples were taken in 2 tubes with EDTA, in 60 patients referred by the attending physician for viral load tests as part of their routine control of HIV/AIDS, and were

  12. Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda.

    Science.gov (United States)

    Asiimwe, Stephen B; Fatch, Robin; Patts, Gregory; Winter, Michael; Lloyd-Travaglini, Christine; Emenyonu, Nneka; Muyindike, Winnie; Kekibiina, Allen; Blokhina, Elena; Gnatienko, Natalia; Kruptisky, Evgeny; Cheng, Debbie M; Samet, Jeffrey H; Hahn, Judith A

    2017-11-01

    In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log 10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log 10 viral load than beer/low-ethanol-content cocktail drinkers (β = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log 10 HIV viral load (β = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the

  13. Importance of Viral Sequence Length and Number of Variable and Informative Sites in Analysis of HIV Clustering.

    Science.gov (United States)

    Novitsky, Vlad; Moyo, Sikhulile; Lei, Quanhong; DeGruttola, Victor; Essex, M

    2015-05-01

    To improve the methodology of HIV cluster analysis, we addressed how analysis of HIV clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering and tree certainty was compared between 401 HIV-1C near full-length genome sequences and subgenomic regions retrieved from the LANL HIV Database. Sliding window analysis was based on 99 windows of 1,000 bp and 45 windows of 2,000 bp. Potential associations between the extent of HIV clustering and sequence length and the number of variable and informative sites were evaluated. The near full-length genome HIV sequences showed the highest extent of HIV clustering and the highest tree certainty. At the bootstrap threshold of 0.80 in maximum likelihood (ML) analysis, 58.9% of near full-length HIV-1C sequences but only 15.5% of partial pol sequences (ViroSeq) were found in clusters. Among HIV-1 structural genes, pol showed the highest extent of clustering (38.9% at a bootstrap threshold of 0.80), although it was significantly lower than in the near full-length genome sequences. The extent of HIV clustering was significantly higher for sliding windows of 2,000 bp than 1,000 bp. We found a strong association between the sequence length and proportion of HIV sequences in clusters, and a moderate association between the number of variable and informative sites and the proportion of HIV sequences in clusters. In HIV cluster analysis, the extent of detectable HIV clustering is directly associated with the length of viral sequences used, as well as the number of variable and informative sites. Near full-length genome sequences could provide the most informative HIV cluster analysis. Selected subgenomic regions with a high extent of HIV clustering and high tree certainty could also be considered as a second choice.

  14. HIV-Specific CD8+ T Cell-Mediated Viral Suppression Correlates With the Expression of CD57

    DEFF Research Database (Denmark)

    Jensen, Sanne S; Tingstedt, Jeanette Linnea; Larsen, Tine Kochendorf

    2016-01-01

    BACKGROUND: Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44...

  15. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

    Directory of Open Access Journals (Sweden)

    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  16. Predictors of CD4 health and viral suppression outcomes for formerly homeless people living with HIV/AIDS in scattered site supportive housing.

    Science.gov (United States)

    Bowen, Elizabeth A; Canfield, James; Moore, Suzanne; Hines, Midge; Hartke, Brent; Rademacher, Chrissy

    2017-11-01

    Stable housing is key to improving health outcomes for people living with HIV/AIDS. Though many formerly homeless HIV positive individuals reside in supportive housing, little research has examined biometric HIV health outcomes for residents of these programs. Through a community-based research partnership, this study analyzed secondary data from a Shelter Plus Care supportive housing program in Cincinnati, Ohio to examine the likelihood of participants achieving a healthy CD4 count (>500 cells/mm 3 ) and viral suppression (viral load housing and to identify participant characteristics associated with these outcomes. The study sample was 86 participants who entered the program between 2008 and 2016, including 50 current residents and 36 exited participants. Participants' average length of stay in Shelter Plus Care was 35.2 months (range 3.2-108.1 months) during the study period. Bivariate analysis indicated statistically significant improvements on both outcome variables, with 45% of participants achieving a healthy CD4 count and 79% achieving viral suppression by program exit or most recent time point. Participants who had health insurance at intake and who had never been incarcerated were more likely to achieve viral suppression, and longer length of stay in the program was also positively associated with viral suppression. These results add to the literature on the relationship between housing conditions and HIV health outcomes by demonstrating that residence in supportive housing is associated with improvements in CD4 count and viral load for a sample of formerly homeless persons living with HIV/AIDS, two-thirds of whom had co-occurring physical health, mental health, or substance abuse problems. Further research collaborations should expand on these findings to examine the service packages that are associated with optimal HIV health outcomes for supportive housing residents.

  17. Behavioral and Other Characteristics Associated with HIV Viral Load in an Outpatient Clinic.

    Directory of Open Access Journals (Sweden)

    Paul L Sacamano

    Full Text Available Persons living with HIV (PLWH who are engaged in care, yet not virally suppressed, represent a risk for transmission and opportunity for risk reduction interventions. This study describes characteristics of an outpatient clinic cohort of PLWH by laboratory confirmed viral suppression status and examines associations with demographics and sexual and drug use behaviors gathered through questionnaire. From a sample of 500 clinic patients, 438 were prescribed antiretroviral treatment (ART and 62 were not. Among the 438 on ART, 72 (16.4% were not virally suppressed at the most recent lab draw. Compared to individuals with a suppressed viral load, those that were unsuppressed were more likely to: be black (79.2% vs. 64.2%; p = 0.014; earn below $25,000/year (88.9% vs. 65.0%; p < 0.001; be of a younger age (47.8 vs. 50.0 mean years; p = 0.009; be on opiate substitution (14.1% vs. 6.3%; p = 0.023; and acknowledge poly-substance (38.9% vs. 24.4%; p = 0.012 and excessive alcohol use (13.9% vs. 6.0%; p = 0.019. Conversely, a smaller proportion of those with an unsuppressed viral load had multiple sex partners in the previous 30 days (39.8% vs. 58.5%; p = 0.003. In multivariable regression of those on ART, the prevalence of an unsuppressed viral load was 3% lower with each increasing year of age (aPR: 0.97; 95% CI: 0.95, 0.99 and 47% lower with income over $25,000/year (aPR: 0.33; 95% CI: 0.16, 0.70. In a separate analysis of all 500 subjects, ART was less frequently prescribed to blacks compared to whites, heterosexuals, those with lower education and income, and persons with active substance use. Findings confirm that a large proportion of PLWH and engaged in care were not virally suppressed and continued behaviors that risk transmission, indicating the need for screening, prevention counseling and access to ancillary services to lower the incidence of HIV infections.

  18. Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection.

    Science.gov (United States)

    Fidler, Sarah; Olson, Ashley D; Bucher, Heiner C; Fox, Julie; Thornhill, John; Morrison, Charles; Muga, Roberto; Phillips, Andrew; Frater, John; Porter, Kholoud

    2017-02-01

    Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research. Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders. Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0-35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.

  19. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey.

    Science.gov (United States)

    Nguyen, Quyen Le Thi; Nguyen, Long Hoang; Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W B; Ho, Roger C M

    2017-01-01

    Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients' health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients' WTP for CD4 cell count and viral load testing. HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6-8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3-20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients.

  20. Host and viral determinants for MxB restriction of HIV-1 infection.

    Science.gov (United States)

    Matreyek, Kenneth A; Wang, Weifeng; Serrao, Erik; Singh, Parmit Kumar; Levin, Henry L; Engelman, Alan

    2014-10-25

    Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26-90 that contribute to MxB activity, finding sequences present within residues 27-50 particularly important. MxB inhibits HIV-1 by interfering with minimally two steps of infection

  1. Recent developments in the effort to cure HIV infection: going beyond N = 1

    Science.gov (United States)

    Siliciano, Janet D.; Siliciano, Robert F.

    2016-01-01

    Combination antiretroviral therapy (ART) can suppress plasma HIV to undetectable levels, allowing HIV-infected individuals who are treated early a nearly normal life span. Despite the clear ability of ART to prevent morbidity and mortality, it is not curative. Even in individuals who have full suppression of viral replication on ART, there are resting memory CD4+ T cells that harbor stably integrated HIV genomes, which are capable of producing infectious virus upon T cell activation. This latent viral reservoir is considered the primary obstacle to the development of an HIV cure, and recent efforts in multiple areas of HIV research have been brought to bear on the development of strategies to eradicate or develop a functional cure for HIV. Reviews in this series detail progress in our understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies. PMID:26829622

  2. Mapping the binding interface between an HIV-1 inhibiting intrabody and the viral protein Rev.

    Directory of Open Access Journals (Sweden)

    Thomas Vercruysse

    Full Text Available HIV-1 Rev is the key protein in the nucleocytoplasmic export and expression of the late viral mRNAs. An important aspect for its function is its ability to multimerize on these mRNAs. We have recently identified a llama single-domain antibody (Nb190 as the first inhibitor targeting the Rev multimerization function in cells. This nanobody is a potent intracellular antibody that efficiently inhibits HIV-1 viral production. In order to gain insight into the Nb190-Rev interaction interface, we performed mutational and docking studies to map the interface between the nanobody paratope and the Rev epitope. Alanine mutants of the hyper-variable domains of Nb190 and the Rev multimerization domains were evaluated in different assays measuring Nb190-Rev interaction or viral production. Seven residues within Nb190 and five Rev residues are demonstrated to be crucial for epitope recognition. These experimental data were used to perform docking experiments and map the Nb190-Rev structural interface. This Nb190-Rev interaction model can guide further studies of the Nb190 effect on HIV-1 Rev function and could serve as starting point for the rational development of smaller entities binding to the Nb190 epitope, aimed at interfering with protein-protein interactions of the Rev N-terminal domain.

  3. HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya.

    Science.gov (United States)

    Kantor, Rami; DeLong, Allison; Balamane, Maya; Schreier, Leeann; Lloyd, Robert M; Injera, Wilfred; Kamle, Lydia; Mambo, Fidelis; Muyonga, Sarah; Katzenstein, David; Hogan, Joseph; Buziba, Nathan; Diero, Lameck

    2014-01-01

    Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma

  4. Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

    Science.gov (United States)

    Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

    2011-07-01

    The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

  5. The diagnosis of symptomatic acute antiretroviral syndrome during the window period with antigen/antibody testing and HIV viral load

    Directory of Open Access Journals (Sweden)

    Daniel O. Griffin

    Full Text Available Despite much focus on moving toward a cure to end the epidemic human immunodeficiency virus (HIV epidemic there are still thousands of new infections occurring every year in the United States. Although there is ongoing transmission of HIV in the United States and a growing population of people living with HIV, the acute presentation of HIV infection can be challenging to diagnose and is often not considered when patients present to healthcare providers. Although in certain states there are HIV testing laws that require that all persons between the ages of 13 and 64 be offered HIV testing in an opt-out approach, many patient presenting with an acute illness, that would warrant diagnostic testing for HIV, leave without having an HIV test performed for either diagnostic or screening purposes.We describe the case of a woman who presented to medical attention with symptoms later confirmed to be due to acute HIV infection. She was initially discharged from the hospital and only underwent HIV testing with confirmation of her diagnosis after readmission. We describe the algorithm where fourth generation testing combined with HIV viral load testing allowed for the diagnosis of acute HIV prior to the development of a specific immunoglobulin response. Consideration of this diagnosis, improved HIV screening, and understanding of the use of antigen/antibody screening tests, combined with Multispot and HIV viral RNA detection, when appropriate, can allow for early diagnosis of HIV before progression of disease and before undiagnosed patient spread the infection to new contacts.

  6. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

  7. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

    2018-04-01

    Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  8. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Directory of Open Access Journals (Sweden)

    Christopher W Peterson

    2018-04-01

    Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  9. Membrane-based, sedimentation-assisted plasma separator for point-of-care applications.

    Science.gov (United States)

    Liu, Changchun; Mauk, Michael; Gross, Robert; Bushman, Frederic D; Edelstein, Paul H; Collman, Ronald G; Bau, Haim H

    2013-11-05

    Often, high-sensitivity, point-of-care (POC) clinical tests, such as HIV viral load, require large volumes of plasma. Although centrifuges are ubiquitously used in clinical laboratories to separate plasma from whole blood, centrifugation is generally inappropriate for on-site testing. Suitable alternatives are not readily available to separate the relatively large volumes of plasma from milliliters of blood that may be needed to meet stringent limit-of-detection specifications for low-abundance target molecules. We report on a simple-to-use, low-cost, pump-free, membrane-based, sedimentation-assisted plasma separator capable of separating a relatively large volume of plasma from undiluted whole blood within minutes. This plasma separator consists of an asymmetric, porous, polysulfone membrane housed in a disposable chamber. The separation process takes advantage of both gravitational sedimentation of blood cells and size exclusion-based filtration. The plasma separator demonstrated a "blood in-plasma out" capability, consistently extracting 275 ± 33.5 μL of plasma from 1.8 mL of undiluted whole blood within less than 7 min. The device was used to separate plasma laden with HIV viruses from HIV virus-spiked whole blood with recovery efficiencies of 95.5% ± 3.5%, 88.0% ± 9.5%, and 81.5% ± 12.1% for viral loads of 35,000, 3500, and 350 copies/mL, respectively. The separation process is self-terminating to prevent excessive hemolysis. The HIV-laden plasma was then injected into our custom-made microfluidic chip for nucleic acid testing and was successfully subjected to reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP), demonstrating that the plasma is sufficiently pure to support high-efficiency nucleic acid amplification.

  10. Dried blood spot HIV-1 RNA quantification using open real-time systems in South Africa and Burkina Faso.

    Science.gov (United States)

    Viljoen, Johannes; Gampini, Sandrine; Danaviah, Sivapragashini; Valéa, Diane; Pillay, Sureshnee; Kania, Dramane; Méda, Nicolas; Newell, Marie-Louise; Van de Perre, Philippe; Rouet, François

    2010-11-01

    There is an urgent need to assess the accuracy/feasibility of using dried blood spots (DBS) for monitoring of HIV-1 viral load in resource-limited settings. A total of 892 DBS from HIV-1-positive pregnant women and their neonates enrolled in the Kesho Bora prevention of mother-to-child transmission trial conducted in Durban (South Africa) and Bobo-Dioulasso (Burkina Faso) between May 2005 and July 2008 were tested for HIV-1 RNA. The combination Nuclisens extraction method (BioMérieux)/Generic HIV Viral Load assay (Biocentric) was performed using one DBS (in Durban) versus 2 DBS (in Bobo-Dioulasso) on 2 distinct open real-time polymerase chain reaction instruments. DBS HIV-1 RNA results were compared with plasma HIV-1 RNA and HIV serology results used as the gold standards. The limits of detection of assays on DBS were 3100 and 1550 copies per milliliter in Durban and Bobo-Dioulasso, respectively. DBS HIV-1 RNA values correlated significantly with plasma levels (n = 327; R = 0.7351) and were uniformly distributed according to duration of DBS storage at -20°C (median duration, 280 days). For early infant diagnosis, the sensitivity and specificity were 100% (95% confidence interval: 97.2 to 100.0 and 96.5 to 100.0, respectively). HIV-1 viral load kinetics in DNase-pretreated DBS were similar to those obtained in plasma specimens among 13 patients receiving antiretroviral treatment. HIV-1 RNA findings from serial infant DBS collected prospectively (n = 164) showed 100% concordance with HIV serology at 18 months of life. Our findings strongly advocate the implementation of DBS HIV-1 RNA testing in remote areas from low-income and middle-income countries.

  11. Validation of Performance of the Gen-Probe Human Immunodeficiency Virus Type 1 Viral Load Assay with Genital Swabs and Breast Milk Samples

    Science.gov (United States)

    DeVange Panteleeff, Dana; Emery, Sandra; Richardson, Barbra A.; Rousseau, Christine; Benki, Sarah; Bodrug, Sharon; Kreiss, Joan K.; Overbaugh, Julie

    2002-01-01

    Human immunodeficiency type 1 (HIV-1) continues to spread at an alarming rate. The virus may be transmitted through blood, genital secretions, and breast milk, and higher levels of systemic virus in the index case, as measured by plasma RNA viral load, have been shown to correlate with increased risk of transmitting HIV-1 both vertically and sexually. Less is known about the correlation between transmission and HIV-1 levels in breast milk or genital secretions, in part because reliable quantitative assays to detect HIV-1 in these fluids are not available. Here we show that the Gen-Probe HIV-1 viral load assay can be used to accurately quantify viral load in expressed breast milk and in cervical and vaginal samples collected on swabs. Virus could be quantified from breast milk and swab samples spiked with known amounts of virus, including HIV-1 subtypes A, C, and D. As few as 10 copies of HIV-1 RNA could be detected above background threshold levels in ≥77% of assays performed with spiked breast milk supernatants and mock swabs. In genital swab samples from HIV-1-infected women, similar levels of HIV-1 RNA were consistently detected in duplicate swabs taken from the same woman on the same clinic visit, suggesting that the RNA values from a single swab sample can be used to measure genital viral load. PMID:12409354

  12. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

  13. HIV Viral Load Trends in Six Eastern Caribbean Countries Utilizing a Regional Laboratory Referral Service: Implications for Treatment as Prevention.

    Science.gov (United States)

    Landis, R Clive; Carmichael-Simmons, Kelly; Hambleton, Ian R; Best, Anton

    2015-01-01

    Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS), Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL) offered by The Ladymeade Reference Unit (LRU) Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service. Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama). VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples. A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2%) mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001). We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network.

  14. HIV Viral Load Trends in Six Eastern Caribbean Countries Utilizing a Regional Laboratory Referral Service: Implications for Treatment as Prevention.

    Directory of Open Access Journals (Sweden)

    R Clive Landis

    Full Text Available Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS, Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL offered by The Ladymeade Reference Unit (LRU Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service.Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama. VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples.A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2% mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001.We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network.

  15. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    Science.gov (United States)

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  16. Food insecurity, CD4 counts, and incomplete viral suppression among HIV+ patients from Texas Children's Hospital: A pilot study

    Science.gov (United States)

    Our goal was to determine the relationship between food insecurity and CD4 counts and viral suppression among pediatric HIV-positive patients. Food insecurity was assessed by validated survey. CD4 counts and viral load were abstracted from patients’ charts. We used linear regression for the dependen...

  17. Change in fibrosis score as a predictor of mortality among HIV-infected patients with viral hepatitis.

    Science.gov (United States)

    Jain, Mamta K; Seremba, Emmanuel; Bhore, Rafia; Dao, Doan; Joshi, Reeti; Attar, Nahid; Yuan, He-Jun; Lee, William M

    2012-02-01

    Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

  18. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

    Directory of Open Access Journals (Sweden)

    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  19. Seroprevalence occurrence of viral hepatitis and HIV among hemodialysis patients

    Science.gov (United States)

    Kamal, Inass Mahmood; Mutar Mahdi, Batool

    2018-05-01

    Background: Patients with chronic renal failure (CRF) were on maintenance invasive haemodialysis (HD) procedure. This procedure by itself affects immunity of the patients and became more susceptible to viral infections. Aim of the study: to investigate the occurrence of HBV, HCV and HIV infections in patients with hemodialysis. Patients and methods: A retrospective study of 430 end-stage renal failure patients, referred to hemodialysis department at Al-Kindy Teaching Hospital, Baghdad-Iraq from Junuary-2015 to Junuary-2017. Patients were investigated for HBs-Ag using enzyme-labeled antigen test (Foresight-EIA-USA ), HCV- Abs (IgG) specific immunoglobulin using a HCV enzyme-labeled antigen test (Foresight-EIA-USA) and anti HIV Abs (IgG) using enzyme-labeled antigen test (Foresight-EIA-USA). Results: The frequency of HBV infection in the first year was not significant between males (1.11%) and females (0.00%)(P = 0.295). About HCV also there are no significant differences between males (12.63%) and females (9.31%)(P = 0.347). After one year of follow up the frequencies of HBV and HCV were not significant between two sexes. Additionally, no any one of the patients had HIV infection. Conclusions: This study brings a light on that HBV and HCV were having the same frequencies in both genders and lower occurrence with time. Furthermore, HIV was not detected in those patients.

  20. Seroprevalence occurrence of viral hepatitis and HIV among hemodialysis patients.

    Science.gov (United States)

    Kamal, Inass Mahmood Abid; Mahdi, Batool Mutar

    2018-05-01

    Patients with chronic renal failure (CRF) were on maintenance invasive hemodialysis (HD) procedure. This procedure by itself affects immunity of the patients and became more susceptible to viral infections. to investigate the occurrence of HBV, HCV and HIV infections in patients with hemodialysis. A retrospective study of 430 end-stage renal failure patients, referred to hemodialysis department at XXXX Teaching Hospital, Baghdad-Iraq from January-2015 to January-2017. Patients were investigated for HBs-Ag using enzyme-labeled antigen test (Foresight-EIA-USA), HCV- Abs (IgG) specific immunoglobulin using an HCV enzyme-labeled antigen test (Foresight-EIA-USA)and anti - HIV Abs (IgG) using enzyme-labeled antigen test (Foresight-EIA-USA). The frequency of HBV infection in the first year was not significant between males (1.11%) and females (0.00%) (P = 0.295). About HCV also there are no significant differences between males (12.63%) and females (9.31%) (P = 0.347). After one year of follow up the frequencies of HBV and HCV were not significant between two sexes. Additionally, no any one of the patients had HIV infection. This study brings a light on that HBV and HCV were having the same frequencies in both genders and lower occurrence with time. Furthermore, HIV was not detected in those patients.

  1. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  2. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  3. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Holger B Kramer

    2010-05-01

    Full Text Available The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, beta-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA occurred as early as 5-7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT, termed virus inhibitory peptide (VIRIP, was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

  4. Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.

    Science.gov (United States)

    Bertels, Frederic; Marzel, Alex; Leventhal, Gabriel; Mitov, Venelin; Fellay, Jacques; Günthard, Huldrych F; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Battegay, Manuel; Rauch, Andri; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Schmid, Patrick; Scherrer, Alexandra U; Müller, Viktor; Bonhoeffer, Sebastian; Kouyos, Roger; Regoes, Roland R

    2018-01-01

    Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

    Directory of Open Access Journals (Sweden)

    Sandra A Springer

    Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  6. Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4+ Level

    Science.gov (United States)

    de Freitas, Vera Lúcia Teixeira; da Silva, Sheila Cristina Vicente; Sartori, Ana Marli; Bezerra, Rita Cristina; Westphalen, Elizabeth Visone Nunes; Molina, Tatiane Decaris; Teixeira, Antonio R. L.; Ibrahim, Karim Yaqub; Shikanai-Yasuda, Maria Aparecida

    2011-01-01

    Background Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4+ cells or the CD4+/CD8+ ratio. Conclusions qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4+ cells/mm3 and the CD4+/CD8+ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy. PMID

  7. A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication.

    Science.gov (United States)

    Herzig, Eytan; Voronin, Nickolay; Kucherenko, Nataly; Hizi, Amnon

    2015-08-01

    The process of reverse transcription (RTN) in retroviruses is essential to the viral life cycle. This key process is catalyzed exclusively by the viral reverse transcriptase (RT) that copies the viral RNA into DNA by its DNA polymerase activity, while concomitantly removing the original RNA template by its RNase H activity. During RTN, the combination between DNA synthesis and RNA hydrolysis leads to strand transfers (or template switches) that are critical for the completion of RTN. The balance between these RT-driven activities was considered to be the sole reason for strand transfers. Nevertheless, we show here that a specific mutation in HIV-1 RT (L92P) that does not affect the DNA polymerase and RNase H activities abolishes strand transfer. There is also a good correlation between this complete loss of the RT's strand transfer to the loss of the DNA clamp activity of the RT, discovered recently by us. This finding indicates a mechanistic linkage between these two functions and that they are both direct and unique functions of the RT (apart from DNA synthesis and RNA degradation). Furthermore, when the RT's L92P mutant was introduced into an infectious HIV-1 clone, it lost viral replication, due to inefficient intracellular strand transfers during RTN, thus supporting the in vitro data. As far as we know, this is the first report on RT mutants that specifically and directly impair RT-associated strand transfers. Therefore, targeting residue Leu92 may be helpful in selectively blocking this RT activity and consequently HIV-1 infectivity and pathogenesis. Reverse transcription in retroviruses is essential for the viral life cycle. This multistep process is catalyzed by viral reverse transcriptase, which copies the viral RNA into DNA by its DNA polymerase activity (while concomitantly removing the RNA template by its RNase H activity). The combination and balance between synthesis and hydrolysis lead to strand transfers that are critical for reverse transcription

  8. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

    Directory of Open Access Journals (Sweden)

    Melanie Thompson

    Full Text Available GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA boost vaccine (GOVX-B11, was undertaken in HIV infected participants on antiretroviral treatment (ART to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI. Nine men who began antiretroviral therapy (ART within 18 months of seroconversion and had sustained plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine.clinicaltrials.gov NCT01378156.

  9. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

    Science.gov (United States)

    Thompson, Melanie; Heath, Sonya L; Sweeton, Bentley; Williams, Kathy; Cunningham, Pamela; Keele, Brandon F; Sen, Sharon; Palmer, Brent E; Chomont, Nicolas; Xu, Yongxian; Basu, Rahul; Hellerstein, Michael S; Kwa, Suefen; Robinson, Harriet L

    2016-01-01

    GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA) boost vaccine (GOVX-B11), was undertaken in HIV infected participants on antiretroviral treatment (ART) to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI). Nine men who began antiretroviral therapy (ART) within 18 months of seroconversion and had sustained plasma HIV-1 RNA HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine. clinicaltrials.gov NCT01378156.

  10. HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

    Science.gov (United States)

    Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

    2018-03-01

    HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

  11. [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads].

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    Orta Mira, Nieves; Serrano, María del Remedio Guna; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Cardona, Concepción Gimeno

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean ± 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Δ<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean ± 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable. Copyright © 2011 Elsevier España S.L. All rights reserved.

  12. “Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk: Findings from a Randomized Controlled Trial”

    Science.gov (United States)

    KURTH, Ann E.; SPIELBERG, Freya; CLELAND, Charles M.; LAMBDIN, Barrot; BANGSBERG, David R.; FRICK, Pamela A.; SEVERYNEN, Anneleen O.; CLAUSEN, Marc; NORMAN, Robert G.; LOCKHART, David; SIMONI, Jane M.; HOLMES, King K.

    2014-01-01

    Objective Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design Longitudinal RCT. Settings An academic HIV clinic and a community-based organization in Seattle. Subjects 240 HIV-positive adults on ART; 209 completed nine-month follow-up (87% retention). Intervention Randomization to computerized counseling or assessment-only, 4 sessions over 9 months. Main Outcome Measures HIV-1 viral suppression, and self-reported ART adherence, and transmission risks, compared using generalized estimating equations. Results Overall, intervention participants had reduced viral load (VL): mean 0.17 log10 decline, versus 0.13 increase in controls, p = 0.053, and significant difference in ART adherence baseline to 9 months (p = 0.046). Their sexual transmission risk behaviors decreased (OR = 0.55, p = 0.020), a reduction not seen among controls (OR = 1.1, p = 0.664), and a significant difference in change (p = 0.040). Intervention effect was driven by those most in need: among those with detectable virus at baseline (>30 copies/milliliter, n=89), intervention effect was mean 0.60 log10 VL decline versus 0.15 increase in controls, p=0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, p = 0.038. Conclusions Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior. PMID:24384803

  13. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

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    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  14. Disclosure behaviour and experienced reactions in patients with HIV versus chronic viral hepatitis or diabetes mellitus in Germany.

    Science.gov (United States)

    Kittner, J M; Brokamp, F; Jäger, B; Wulff, W; Schwandt, B; Jasinski, J; Wedemeyer, H; Schmidt, R E; Schattenberg, J M; Galle, P R; Schuchmann, M

    2013-01-01

    Disclosure is a prerequisite to receive disease-specific social support. However, in the case of a stigmatised disease, it can also lead to discrimination. We aimed to assess disclosure rates of HIV patients and the reactions they encountered in comparison to patients with chronic viral hepatitis or diabetes mellitus and patients' general perception of disease-specific discrimination. We constructed a self-report questionnaire, anonymously assessing the size of the social environment, the persons who had been informed, and the experienced reactions as perceived by the disclosing patients, to be rated on 1-4 point Likert scales. In addition, patients were asked whether they perceive general discrimination in Germany. One hundred and seventy-one patients were asked to participate. Five rejected, thus questionnaires from 83 patients with HIV, 42 patients with chronic viral hepatitis B (n = 9) or C (n = 33), and 41 patients with insulin-dependent diabetes mellitus (type I n = 14, type II n = 27) were analysed. Whereas the size of the social environment did not differ, HIV-infected patients were least likely to disclose their disease (60.7%, SD ± 31.9) to their social environment as compared to patients with chronic viral hepatitis (84.2 ± 23.3%, pdiabetes mellitus (94.4 ± 10.3%, ppatient group, the mean disclosure rate was highest to partners (90.9%), followed by the public environment (65.2%), friends (59.4%) and family members (43.8%). HIV patients experienced supportive reactions after 79.3 ± 26.4% of disclosures, which was the case in 91.4 ± 19.6% and 75.7 ± 36.1% of patients with hepatitis or diabetes mellitus, respectively. 69.5% of HIV patients stated to perceive general discrimination in Germany. We conclude that HIV patients had experienced supportive reactions after the majority of disclosures, but the low rate points out that their information strategy had been very selective. Societal discrimination of HIV patients is still an issue and needs to be

  15. Cervical Shedding of HIV-1 RNA Among Women With Low Levels of Viremia While Receiving Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Neely, Michael N.; Benning, Lorie; Xu, Jiaao; Strickler, Howard D.; Greenblatt, Ruth M.; Minkoff, Howard; Young, Mary; Bremer, James; Levine, Alexandra M.; Kovacs, Andrea

    2011-01-01

    Background Among women with low o r undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. Methods We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women’s Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. Results Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). Conclusions This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners. PMID:17106279

  16. Fluorescent reporter signals, EGFP and DsRed, encoded in HIV-1 facilitate the detection of productively infected cells and cell-associated viral replication levels

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    Kazutaka eTerahara

    2012-01-01

    Full Text Available Flow cytometric analysis is a reliable and convenient method for investigating molecules at the single cell level. Previously, recombinant human immunodeficiency virus type 1 (HIV-1 strains were constructed that express a fluorescent reporter, either enhanced green fluorescent protein or DsRed, which allow the monitoring of HIV-1-infected cells by flow cytometry. The present study further investigated the potential of these recombinant viruses in terms of whether the HIV-1 fluorescent reporters would be helpful in evaluating viral replication based on fluorescence intensity. When primary CD4+ T cells were infected with recombinant viruses, the fluorescent reporter intensity measured by flow cytometry was associated with the level of CD4 downmodulation and Gag p24 expression in infected cells. Interestingly, some HIV-1-infected cells, in which CD4 was only moderately downmodulated, were reporter-positive but Gag p24-negative. Furthermore, when the activation status of primary CD4+ T cells was modulated by T cell receptor-mediated stimulation, we confirmed the preferential viral production upon strong stimulation and showed that the intensity of the fluorescent reporter within a proportion of HIV-1-infected cells was correlated with the viral replication level. These findings indicate that a fluorescent reporter encoded within HIV-1 is useful for the sensitive detection of productively-infected cells at different stages of infection and for evaluating cell-associated viral replication at the single cell level.

  17. Measuring population transmission risk for HIV: an alternative metric of exposure risk in men who have sex with men (MSM in the US.

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    Colleen F Kelley

    Full Text Available Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL, population viral load (PVL, percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities.Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM, we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. MSM with plasma VL>400 copies/mL were defined as having 'transmission risk'. We calculated HIV prevalence, CVL, PVL, percent of HIV-positive with undetectable viral loads, and prevalence of plasma VL>400 copies/ml (%VL400 for black and white MSM. We used Monte Carlo simulation incorporating data on sexual mixing by race to estimate exposure of black and white HIV-negative MSM to a partner with transmission risk via unprotected anal intercourse (UAI. Of 709 MSM recruited, 42% (168/399 black and 14% (44/310 white MSM tested HIV-positive (p<.0001. No significant differences were seen in CVL, PVL, or percent of HIV positive with undetectable viral loads. The %VL400 was 25% (98/393 for black vs. 8% (25/310 for white MSM (p<.0001. Black MSM with 2 UAI partners were estimated to have 40% probability (95% CI: 35%, 45% of having ≥1 UAI partner with transmission risk vs. 20% for white MSM (CI: 15%, 24%.Despite similarities in other metrics, black MSM in our cohort are three times as likely as white MSM to have HIV transmission risk. With comparable risk behaviors, HIV-negative black MSM have a substantially higher likelihood of encountering a UAI partner at risk of transmitting HIV. Our results support increasing HIV testing, linkage to care, and antiretroviral treatment of HIV-positive MSM to reduce prevalence of those with transmission risk, particularly for black MSM.

  18. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells.

    Science.gov (United States)

    Oufir, Mouhssin; Bisset, Leslie R; Hoffmann, Stefan R K; Xue, Gongda; Klauser, Stephan; Bergamaschi, Bianca; Gervaix, Alain; Böni, Jürg; Schüpbach, Jörg; Gutte, Bernd

    2011-01-01

    An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  19. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

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    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  20. Seroprevalence occurrence of viral hepatitis and HIV among hemodialysis patients

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    Inass Mahmood Abid Kamal

    2018-05-01

    Full Text Available Background: Patients with chronic renal failure (CRF were on maintenance invasive hemodialysis (HD procedure. This procedure by itself affects immunity of the patients and became more susceptible to viral infections. Aim of the study: to investigate the occurrence of HBV, HCV and HIV infections in patients with hemodialysis. Patients and methods: A retrospective study of 430 end-stage renal failure patients, referred to hemodialysis department at XXXX Teaching Hospital, Baghdad-Iraq from January-2015 to January-2017. Patients were investigated for HBs-Ag using enzyme-labeled antigen test (Foresight-EIA-USA, HCV- Abs (IgG specific immunoglobulin using an HCV enzyme-labeled antigen test (Foresight-EIA-USAand anti - HIV Abs (IgG using enzyme-labeled antigen test (Foresight-EIA-USA. Results: The frequency of HBV infection in the first year was not significant between males (1.11% and females (0.00% (P = 0.295. About HCV also there are no significant differences between males (12.63% and females (9.31% (P = 0.347. After one year of follow up the frequencies of HBV and HCV were not significant between two sexes. Additionally, no any one of the patients had HIV infection. Conclusions: This study brings a light on that HBV and HCV were having the same frequencies in both genders and lower occurrence with time. Furthermore, HIV was not detected in those patients. Keywords: Virus, Hemodialysis, Infection

  1. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

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    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  2. Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load.

    NARCIS (Netherlands)

    Arnaiz, J.A.; Mallolas, J.; Podzamczer, D.; Gerstoft, J.; Lundgren, J.D.; Cahn, P.; Fatkenheuer, G.; D'Arminio-Monforte, A.; Casiro, A.; Reiss, P.; Burger, D.M.; Stek Jr, M.; Gatell, J.M.

    2003-01-01

    OBJECTIVE: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). DESIGN: Multicentre, international,

  3. Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load

    NARCIS (Netherlands)

    Arnaiz, Juan A.; Mallolas, Josep; Podzamczer, Daniel; Gerstoft, Jan; Lundgren, Jens D.; Cahn, Pedro; Fätkenheuer, Gerd; D'Arminio-Monforte, Antonella; Casiró, Arnaldo; Reiss, Peter; Burger, David M.; Stek, Michael; Gatell, José M.

    2003-01-01

    Objective: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). Design: Multicentre, international,

  4. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Science.gov (United States)

    Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

    2013-01-01

    To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, pgenital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  5. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

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    Sharma Gaurav

    2011-01-01

    Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.

  6. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART during acute HIV-1 infection: An observational study.

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    Timothy J Henrich

    2017-11-01

    Full Text Available It is unknown if extremely early initiation of antiretroviral therapy (ART may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male and 12 days (Participant B; 31-year-old male after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI following 32 weeks of continuous ART.Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF, plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA. Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse, but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input

  7. Comparison of HIV DNA and RNA in gut-associated lymphoid tissue of HIV-infected controllers and noncontrollers.

    Science.gov (United States)

    Hatano, Hiroyu; Somsouk, Ma; Sinclair, Elizabeth; Harvill, Kara; Gilman, Lee; Cohen, Michelle; Hoh, Rebecca; Hunt, Peter W; Martin, Jeffrey N; Wong, Joseph K; Deeks, Steven G; Yukl, Steven A

    2013-09-10

    HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers. Cross-sectional cohort study. Colorectal biopsy pieces were obtained from five untreated noncontrollers, five ART-suppressed patients, and nine untreated controllers. Rectal HIV DNA was lower in controllers (median 496 copies/10(6) CD4 T cells) than in untreated noncontrollers (117483 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (6116 copies/10(6) CD4 T cells, P = 0.004). Similarly, rectal HIV RNA was lower in controllers (19 copies/10(6) CD4 T cells) than in noncontrollers (15210 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (1625 copies/10(6) CD4+ T cells, P = 0.0599). Rectal HIV RNA/DNA ratios were not statistically different between the three groups. Despite being able to maintain very low plasma HIV RNA levels in the absence of antiretroviral therapy (ART), HIV-infected controllers have readily measurable levels of HIV DNA and RNA in GALT. As expected, controllers had lower rectal HIV DNA and RNA compared with untreated noncontrollers and ART-suppressed individuals. Compared with the mechanisms of 'natural' viral control of controllers, long-term ART does not reduce the total HIV reservoir to the level of controllers.

  8. Produção de interleucina-10 na gestação reduz a taxa de replicação do HIV-1 em culturas de linfócitos maternos Interleukin-10 production during pregnancy reduces HIV-1 replicaction in cultures of maternal lymphocytes

    Directory of Open Access Journals (Sweden)

    Bruno Monção Paolino

    2005-07-01

    Full Text Available OBJETIVO: avaliar a proliferação de células T e a produção de citocinas em gestantes infectadas pelo HIV-1 e seu impacto na replicação viral in vitro. MÉTODOS: sangue periférico de 12 gestantes infectadas pelo HIV-1 e de seus neonatos, bem como de 10 gestantes HIV-1 negativas, foi colhido e a quantidade de linfócitos TCD4+ e TCD8+ periféricos foi avaliada por citometria de fluxo. Para obter plasma ou células mononucleares periféricas (PBMC, as amostras foram centrifugadas na ausência ou presença de um gradiente de Ficoll-Hypaque, respectivamente. As PBMC foram mantidas em cultura por sete dias na presença de fito-hemaglutinina mais IL-2 recombinante e a resposta linfoproliferativa de células T foi analisada pelo método de exclusão em azul de Trypan. Em alguns experimentos, as culturas foram mantidas na presença adicional de anticorpo anti-IL-10. Os plasmas e sobrenadantes das culturas de PBMC ativadas foram submetidos à análise da produção de citocinas, pelo método ELISA indireto, e a carga viral, detectada pelo RT-PCR. RESULTADOS: independente da carga viral plasmática, a resposta linfoproliferativa em culturas de células obtidas de gestantes infectadas pelo HIV foi inferior às amostras normais [4,2±0,37 vs 2,4±0,56 (x 10(6 células/mL; pPURPOSE: to evaluate T cell proliferation and cytokine production in HIV-1-infected pregnant women and their impact on in vitro virus replication. METHODS: peripheral blood from 12 HIV-1-infected pregnant women and from their neonates was collected. As control, 10 samples from non-infected pregnants were also colleted. The CD4+ and CD8+ T cell counts were assayed by flow cytometry. Peripheral blood mononuclear cells (PBMC and plasma were obtained by centrifugation with and without Ficoll-Hypaque gradient, respectively. The freshly purified PBMC were kept in cultures for seven days with PHA plus r-IL-2, and the lymphoproliferative response was assayed by Trypan blue dye exclusion

  9. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

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    Mouhssin Oufir

    2011-01-01

    Full Text Available An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  10. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

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    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  11. Association of High-Risk Human Papillomavirus with Genital Tract Mucosal Immune Factors In HIV-Infected Women

    Science.gov (United States)

    Buckley, Niall; Huber, Ashley; Lo, Yungtai; Castle, Philip E.; Kemal, Kimdar; Burk, Robert D.; Strickler, Howard D.; Einstein, Mark H.; Young, Mary; Anastos, Kathryn; Herold, Betsy C.

    2015-01-01

    Problem High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. Method of Study Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n=8), other HR-HPV (n=41), and non-HR-HPV controls (n=79). Results Compared to controls, HR-HPV groups had higher plasma viral loads (p=0.004), lower CD4 cells (p=0.02), more genital tract HIV RNA (p=0.03), greater number of different HPV types (p<0.001), higher cervicovaginal lavage (CVL) IL-1α (p=0.03) and human beta defensin 2 (HBD2) (p=0.049), and less anti-HIVBal activity (p=0.03). HPV-16 remained significantly associated with higher HBD2 (p=0.03), higher IL-1α (p=0.009), and lower anti-HIVBaL activity (p=0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. Conclusion HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health. PMID:26685115

  12. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Direct and dynamic detection of HIV-1 in living cells.

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    Jonas Helma

    Full Text Available In basic and applied HIV research, reliable detection of viral components is crucial to monitor progression of infection. While it is routine to detect structural viral proteins in vitro for diagnostic purposes, it previously remained impossible to directly and dynamically visualize HIV in living cells without genetic modification of the virus. Here, we describe a novel fluorescent biosensor to dynamically trace HIV-1 morphogenesis in living cells. We generated a camelid single domain antibody that specifically binds the HIV-1 capsid protein (CA at subnanomolar affinity and fused it to fluorescent proteins. The resulting fluorescent chromobody specifically recognizes the CA-harbouring HIV-1 Gag precursor protein in living cells and is applicable in various advanced light microscopy systems. Confocal live cell microscopy and super-resolution microscopy allowed detection and dynamic tracing of individual virion assemblies at the plasma membrane. The analysis of subcellular binding kinetics showed cytoplasmic antigen recognition and incorporation into virion assembly sites. Finally, we demonstrate the use of this new reporter in automated image analysis, providing a robust tool for cell-based HIV research.

  14. A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape

    NARCIS (Netherlands)

    Lebbink, Robert Jan; de Jong, Dorien C M; Wolters, Femke; Kruse, Elisabeth M; van Ham, Petra M; Wiertz, Emmanuel J H J; Nijhuis, Monique

    2017-01-01

    HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle

  15. Low Prevalence of Parvovirus 4 in HIV-infected Children in Denmark.

    Science.gov (United States)

    Rosenfeldt, Vibeke; Norja, Päivi; Lindberg, Ellinor; Jensen, Lise; Hedman, Lea; Väisänen, Elina; Li, Xuemeng; Hedman, Klaus; von Linstow, Marie-Louise

    2015-07-01

    Parvovirus 4 (PARV4) has been associated with HIV infection in adults. We examined plasma samples from 46 HIV-infected 0-year-old to 16-year-old children for the presence of PARV4. Four children (8.7%) had detectable PARV4 IgG and 1 had IgM. The result of PARV4 polymerase chain reaction was found to be negative in all patients. PARV4 seropositivity was associated with low CD4 count but not with HIV viral load.

  16. Changes in HIV-1 subtypes B and C genital tract RNA in women and men after initiation of antiretroviral therapy.

    Science.gov (United States)

    Fiscus, Susan A; Cu-Uvin, Susan; Eshete, Abel Tilahun; Hughes, Michael D; Bao, Yajing; Hosseinipour, Mina; Grinsztejn, Beatriz; Badal-Faesen, Sharlaa; Dragavon, Joan; Coombs, Robert W; Braun, Ken; Moran, Laura; Hakim, James; Flanigan, Timothy; Kumarasamy, N; Campbell, Thomas B

    2013-07-01

    Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype. HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C). Despite similar baseline CD4(+) cell counts and blood plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtype B and men with subtype C or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P female genital tract may serve as a reservoir of persistent HIV-1 replication during cART and affect the use of cART to prevent sexual and perinatal transmission of HIV-1.

  17. Clinical value of indicators of cationic proteins, leukocytes myeloperoxidase and fibronectin blood plasma in viral meningitis in children

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    O. G. Kimirilova

    2017-01-01

    Full Text Available Objective: was to establish clinical and diagnostic value of cytochemical indices of peripheral blood leukocytes (cationic protein and myeloperoxidase, fibronectin blood plasma to assess the severity, predict the course and outcome of viral meningitis in children.Subjects and methods. In 450 patients with viral meningitis (enterovirus, arbovirus, parotitic, herpesviral, adenovirus etiology at the age of 14 years, the parameters of the microbicidal system of leukocytes (cation proteins, myeloperoxidase and fibronectin blood plasma were determined. Etiological diagnosis of meningitis was confirmed by release of viral RNA from blood and cerebrospinal fluid by the polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA.The results and conclusion. Found that severe, prolonged duration, lethal outcome of viral meningitis in children are accompanied by sugnificant suppression of cationic proteins, myeloperoxidase, fibronectin blood plasma, maximally expressed in lethal outcomes, compared with the severe form, but with a favorable outcome and control. Settings imbalance cationic proteins, myeloperoxidase, fibronectin blood plasma are objective criteria of the adaptation syndrome that reflects the state of the phagocytosis system in viral meningitis in children and can be considered as additional criteria for predicting the course and outcome of disease.

  18. Asociación de LT-CD4 y carga viral con candidiasis bucal en pacientes VIH/SIDA en Talca, Chile Association between LT-CD4 and the viral load with oral candidiasis in HIV/AIDS patients in Talca, Chile

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    Pedro Brevis Azocar

    2009-12-01

    Full Text Available La candidiasis bucal aparece con frecuencia en las personas infectadas por el virus de la inmunodeficiencia humana (VIH y puede causar diversas manifestaciones clínicas y complicaciones. En los pacientes VIH la carga viral es considerada uno de los principales predictores en la progresión de la enfermedad. Se realizó un estudio en 29 pacientes adultos VIH-positivos para evaluar los niveles de linfocitos T-CD4 y carga viral; se estableció una relación con las manifestaciones de la candidiasis bucal. El análisis estadístico mostró que hubo relación entre la manifestación de la candidiasis bucal y la carga viral, pues en pacientes con cargas virales superiores a 10 000 copias/mL, las lesiones fueron más frecuentes.Oral candidiasis is frequently appearing in persons infected by human immunodeficiency virus (HIV and may to cause many clinical and complications manifestations. In HIV patients the viral load is considered one of the main predictors in disease progression. A study was conducted in 29 HIV-positive adult patients to assess the T-CD4 lymphocyte levels and the viral load establishing a relationship with oral candidiasis manifestations. The statistical analysis showed that there was a relationship between the oral candidiasis manifestation and the viral load since in patients with viral load higher than 10 000 copies/mL, lesions were more frequent.

  19. Polymorphisms in the IFNγ, IL-10, and TGFβ Genes May Be Associated with HIV-1 Infection

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    Felipe Bonfim Freitas

    2015-01-01

    Full Text Available Objective. This study investigated possible associations between the TNFα-308G/A, IFN+874A/T, IL-6-174C/G, IL-10-1082A/G, and TGFβ-509C/T polymorphisms with HIV-1 infection, in addition to correlation of the polymorphisms with clinical markers of AIDS progression, such as levels of CD4+/CD8+ T lymphocytes and plasma viral load. Methods. A total of 216 individuals who were infected with HIV-1 and on antiretroviral therapy (ART and 294 individuals from the uninfected control group were analyzed. Results. All individuals evaluated were negative for total anti-HBc, anti-HCV, anti-T. pallidum, and anti-HTLV-1/2. The polymorphisms were identified by PCR-RFLP. Individuals presenting the IFN+874A allele as well as the AA genotype were more frequent in the HIV-1 infected group compared to the control group (P<0.05, in addition to having lower levels of CD4+ T lymphocytes. The CD8+ T lymphocytes count was significantly lower in individuals with the IL-10-1082 GG genotype. The TGFβ-509TT genotype was associated with higher plasma viral load. Conclusions. The results suggest that the presence of the IFN+874A allele confers susceptibility to HIV-1 infection and a decrease in the number of CD4+ T lymphocytes. In addition, the genotype associated with high serum levels of TGFβ may be associated with an increase in plasma viral load.

  20. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

    Science.gov (United States)

    Montaner, J S; Reiss, P; Cooper, D; Vella, S; Harris, M; Conway, B; Wainberg, M A; Smith, D; Robinson, P; Hall, D; Myers, M; Lange, J M

    1998-03-25

    Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. Double-blind, controlled, randomized trial. University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. Plasma HIV-1 RNA. Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death

  1. Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry.

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    Rachid Sougrat

    2007-05-01

    Full Text Available The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV, are heterodimers of a transmembrane glycoprotein (usually gp41, and a surface glycoprotein (gp120, which binds CD4 on target cells to initiate viral entry. We have used electron tomography to determine the three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells. The trimeric viral envelope glycoprotein surface spikes are heterogeneous in appearance and typically approximately 120 A long and approximately 120 A wide at the distal end. Docking of SIV or HIV-1 on the T cell surface occurs via a neck-shaped contact region that is approximately 400 A wide and consistently consists of a closely spaced cluster of five to seven rod-shaped features, each approximately 100 A long and approximately 100 A wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies, the CCR5 antagonist TAK779, or the peptide entry inhibitor SIVmac251 C34. For virions bound to cells, few trimers were observed away from this cluster at the virion-cell interface, even in cases where virus preparations showing as many as 70 envelope glycoprotein trimers per virus particle were used. This contact zone, which we term the "entry claw", provides a spatial context to understand the molecular mechanisms of viral entry. Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry.

  2. Validating a self-report measure of HIV viral suppression: an analysis of linked questionnaire and clinical data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study.

    Science.gov (United States)

    Carter, Allison; de Pokomandy, Alexandra; Loutfy, Mona; Ding, Erin; Sereda, Paul; Webster, Kath; Nicholson, Valerie; Beaver, Kerrigan; Hogg, Robert S; Kaida, Angela

    2017-03-24

    We assessed the validity of a self-report measure of undetectable viral load (VL) among women with HIV in British Columbia (BC), Canada. Questionnaire data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study was linked with population-based clinical data from the BC Centre for Excellence in HIV/AIDS. Self-reported undetectable VL was assessed by the question: "What was your most recent VL, undetectable (i.e. linked to clinical data. Those unlinked (n = 1), missing self-report VL (n = 18), or missing self-report and laboratory VL (n = 1) were excluded. Among the remaining 336: median age was 44 (IQR 37-51); 96% identified as cis-gender; 84% identified as heterosexual; and 45% identified as Indigenous, 40% White, 8% African, Caribbean, or Black, and 8% other/multiple ethnicities. Overall, 85% self-reported having an undetectable VL while 82% had clinical data indicating viral suppression. The PPV was 93.7 (95% CI 90.2-96.2) indicating that 94% of women who self-reported being undetectable truly were. The NPV was 80.4 (95% CI 66.9-90.2). LR+ was 3.2 (2.1-4.6) and LR- was 0.05 (0.03-0.10). Our self-report measure assessing undetectable VL strongly predicted true viral suppression among Canadian women with HIV. This measure can be used in research settings without laboratory data in regions with high rates of VL testing and suppression.

  3. HIV-1 Viral RNA Dynamics at the Plasma Membrane May Provide Insight into Viral Assembly | Poster

    Science.gov (United States)

    Many aspects of how infectious viruses assemble in cells have yet to be completely deciphered. However, as reported in a recent Journal of Virology paper, researchers may be one step closer to understanding how HIV-1, the virus that causes AIDS, assembles and replicates.

  4. Latent viral reactivation is associated with changes in plasma antimicrobial protein concentrations during long-duration spaceflight

    Science.gov (United States)

    Spielmann, G.; Laughlin, M. S.; Kunz, H.; Crucian, B. E.; Quiriarte, H. D.; Mehta, S. K.; Pierson, D. L.; Simpson, R. J.

    2018-05-01

    Long duration spaceflights are associated with profound dysregulation of the immune system and latent viral reactivations. However, little is known on the impact of long duration spaceflight on innate immunity which raises concerns on crewmembers' ability to fight infections during a mission. The aim of this study was to determine the effects of spaceflight on plasma antimicrobial proteins (AMPs) and how these changes impact latent herpesvirus reactivations. Plasma, saliva and urine samples were obtained from 23 crewmembers before, during and after a 6-month mission on the International Space Station (ISS). Plasma AMP concentrations were determined by ELISA, and saliva Epstein-Barr virus (EBV) and varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. There was a non-significant increase in plasma HNP1-3 and LL-37 during the early and middle stages of the missions, which was significantly associated with changes in viral DNA during and after spaceflight. Plasma HNP1-3 and Lysozyme increased at the late mission stages in astronauts who had exhibited EBV and VZV reactivations during the early flight stages. Following return to Earth and during recovery, HNP1-3 and lysozyme concentrations were associated with EBV and VZV viral DNA levels, reducing the magnitude of viral reactivation. Reductions in plasma LL-37 upon return were associated with greater CMV reactivation. This study shows that biomarkers of innate immunity appeared to be partially restored after 6-months in space and suggests that following adaptation to the space environment, plasma HNP1-3 and lysozyme facilitate the control of EBV and VZV reactivation rate and magnitude in space and upon return on earth. However, the landing-associated decline in plasma LL-37 may enhance the rate of CMV reactivation in astronauts following spaceflight, potentially compromising crewmember health after landing.

  5. Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061.

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    Iris Chen

    Full Text Available HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.A high resolution melting (HRM diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm, and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study visits.Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions and HIV drug resistance (both gag regions were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

  6. SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A.

    Science.gov (United States)

    Luo, Xinlong; Yang, Wei; Gao, Guangxia

    2018-07-01

    Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via passing through the nuclear pore complex. The nuclear membrane-imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here we report that overexpression of SUN1 specifically inhibited infection by HIV-1 but not that by simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription but led to reduced accumulation of the 2-long-terminal-repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA. IMPORTANCE HIV-1 infects both dividing and nondividing cells. The viral preintegration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1: the regulatory

  7. HIV tropism and decreased risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Nancy A Hessol

    2010-12-01

    Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

  8. Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

    Science.gov (United States)

    Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

    2014-05-01

    Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios. © 2013 Wiley Periodicals, Inc.

  9. Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for Determination of HIV-1 Viral Loads in a Cohort of Canadian Patients with Diverse HIV Subtype Infections▿

    OpenAIRE

    Church, Deirdre; Gregson, Daniel; Lloyd, Tracie; Klein, Marina; Beckthold, Brenda; Laupland, Kevin; Gill, M. John

    2010-01-01

    HIV clinics in Canada provide care to an increasing number of patients born outside of Canada with HIV-1 non-B subtype infections. Because the Easy Q HIV-1 v1.2 assay (EQ; bioMérieux) failed to detect some non-B subtype infections, a multiassay HIV-1 viral load (VL) study was conducted with patients with diverse HIV subtype infections. Patients were enrolled from the Southern Alberta HIV Clinic (SAC), Calgary, Alberta, Canada (n = 349) and the McGill HIV Clinic (MHC), Montreal, Quebec, Canada...

  10. Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

    OpenAIRE

    Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

    2002-01-01

    Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

  11. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  12. Eradication of HIV from Tissue Reservoirs: Challenges for the Cure.

    Science.gov (United States)

    Rose, Rebecca; Nolan, David J; Maidji, Ekaterina; Stoddart, Cheryl A; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S

    2018-01-01

    The persistence of HIV infection, even after lengthy and successful combined antiretroviral therapy (cART), has precluded an effective cure. The anatomical locations and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. In this study, we review research supporting the importance of anatomical tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages. We present accumulated research that clearly demonstrates the limitations of using blood-derived cells as a proxy for tissue reservoirs and sanctuaries throughout the body. We cite recent studies that have successfully used deep-sequencing strategies to uncover the complexity of HIV infection and the ability of the virus to evolve despite undetectable plasma viral loads. Finally, we suggest new strategies and highlight the importance of tissue banks for future research.

  13. Overcoming the Constraints of Anti-HIV/CD89 Bispecific Antibodies That Limit Viral Inhibition

    Directory of Open Access Journals (Sweden)

    Xiaocong Yu

    2016-01-01

    Full Text Available Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89 on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection. This is in sharp contrast to viral inhibition using a chemical conjugate of the Fab of these two antibodies. Therefore, we constructed two novel Fab-like bispecific antibody molecules centered on fusion of the IgG1 CH1 domain or CH1-hinge domain to the C-terminus of F240scFv and fusion of the kappa chain CL domain to the C-terminus of 14A8scFv. Both Bi-Fab antibodies showed significant ADCVI activity for multiple clade B and clade C isolates by arming the neutrophils to inhibit HIV infection. The approach presented in this study is unique for HIV immunotherapy in that the impetus of neutralization is to arm and mobilize PMN to destroy HIV and HIV infected cells.

  14. Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. WHS 001 Study Team.

    Science.gov (United States)

    Reichelderfer, P S; Coombs, R W; Wright, D J; Cohn, J; Burns, D N; Cu-Uvin, S; Baron, P A; Coheng, M H; Landay, A L; Beckner, S K; Lewis, S R; Kovacs, A A

    2000-09-29

    To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus. A prospective analysis of 55 HIV-1-infected women. Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load. Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03). HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

  15. Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

    Science.gov (United States)

    Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

    2014-04-01

    Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

  16. [Reproductive options for people living with HIV: 2013 guidelines from the French expert working group].

    Science.gov (United States)

    Mandelbrot, L; Berrebi, A; Rouzioux, C; Partisani, M; Faucher, P; Tubiana, R; Matheron, S; Bujan, L; Morlat, P

    2014-01-01

    The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. High levels of viral suppression among East African HIV-infected women and men in serodiscordant partnerships initiating antiretroviral therapy with high CD4 counts and during pregnancy.

    Science.gov (United States)

    Mujugira, Andrew; Baeten, Jared; Kidoguchi, Lara; Haberer, Jessica; Celum, Connie; Donnell, Deborah; Ngure, Kenneth; Bukusi, Elizabeth; Mugo, Nelly; Asiimwe, Stephen; Odoyo, Josephine; Tindimwebwa, Edna; Bulya, Nulu; Katabira, Elly; Heffron, Renee

    2017-09-13

    People who are asymptomatic and feel healthy, including pregnant women, may be less motivated to initiate ART or achieve high adherence. We assessed whether ART initiation, and viral suppression 6, 12 and 24-months after ART initiation, were lower in HIV-infected members of serodiscordant couples who initiated during pregnancy or with higher CD4 counts. We used data from the Partners Demonstration Project, an open-label study of the delivery of integrated PrEP and ART (at any CD4 count) for HIV prevention among high-risk HIV serodiscordant couples in Kenya and Uganda. Differences in viral suppression (HIV RNA 500 cells/mm3) and during pregnancy were estimated using Poisson regression. Of 865 HIV-infected participants retained after becoming eligible for ART during study follow-up, 95% initiated ART. Viral suppression 24-months after ART initiation was high overall (97%), and comparable among those initiating ART at CD4 counts >500, 351-500 and ≤350 cells/mm3 (96% vs 97% vs 97%; relative risk [RR] 0.98; 95% CI: 0.93-1.03 for CD4 >500 vs <350 and RR 0.99; 95% CI: (0.93-1.06) for CD4 351-500 vs ≤350). Viral suppression was as likely among women initiating ART primarily to prevent perinatal transmission as ART initiation for other reasons (p=0.9 at 6 months and p=0.5 at 12 months). Nearly all HIV-infected partners initiating ART were virally suppressed by 24 months, irrespective of CD4 count or pregnancy status. These findings suggest that people initiating ART at high CD4 counts or due to pregnancy can adhere to ART as well as those starting treatment with symptomatic HIV disease or low CD4 counts.

  18. Role of Gag and lipids during HIV-1 assembly in CD4 T cells and Macrophages

    Directory of Open Access Journals (Sweden)

    Charlotte eMariani

    2014-06-01

    Full Text Available HIV-1 is an RNA enveloped virus that preferentiallyinfects CD4+ T lymphocytes andalso macrophages. In CD4+ T cells, HIV-1mainly buds from the host cell plasma membrane.The viral Gag polyprotein targets theplasma membrane and is the orchestrator ofthe HIV assembly as its expression is sufficientto promote the formation of virus-likeparticles particles carrying a lipidic envelopederiving from the host cell membrane. Certainlipids are enriched in the viral membraneand are thought to play a key role in theassembly process and the envelop composition.A large body of work performed oninfected CD4+ T cells has provided importantknowledge about the assembly process andthe membrane virus lipid composition. WhileHIV assembly and budding in macrophages isthought to follow the same general Gag-drivenmechanism as in T-lymphocytes, the HIV cyclein macrophage exhibits specific features.In these cells, new virions bud from the limitingmembrane of seemingly intracellular compartments,where they accumulate while remaininginfectious. These structures are now oftenreferred to as Virus Containing Compartments(VCCs. Recent studies suggest that VCCsrepresent intracellularly sequestered regionsof the plasma membrane, but their precisenature remains elusive. The proteomic andlipidomic characterization of virions producedby T cells or macrophages has highlightedthe similarity between their composition andthat of the plasma membrane of producercells, as well as their enrichment in acidiclipids, some components of raft lipids andin tetraspanin-enriched microdomains. Greatchances are that Gag promotes the coalescenceof these components into an assemblyplatform from which viral budding takesplace. How Gag exactly interacts with membranelipids and what are the mechanisms involvedin the interaction between the differentmembrane nanodomains within the assemblyplatform remains unclear. Here we review recentliterature regarding the role of Gag andlipids

  19. Predictive factors of plasma HIV suppression during pregnancy: a prospective cohort study in Benin.

    Directory of Open Access Journals (Sweden)

    Lise Denoeud-Ndam

    Full Text Available To investigate the factors associated with HIV1 RNA plasma viral load (pVL below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT in Benin.Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT.HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy.Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area, regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression.This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.

  20. Predictive factors of plasma HIV suppression during pregnancy: a prospective cohort study in Benin.

    Science.gov (United States)

    Denoeud-Ndam, Lise; Fourcade, Camille; Ogouyemi-Hounto, Aurore; Azon-Kouanou, Angèle; d'Almeida, Marcelline; Azondékon, Alain; Alao, Marouf J; Dossou-Gbété, Véronique; Afangnihoun, Aldric; Girard, Pierre-Marie; Cot, Michel; Zannou, Djimon-Marcel

    2013-01-01

    To investigate the factors associated with HIV1 RNA plasma viral load (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT) in Benin. Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT. HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART) for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy. Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area), regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression. This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.

  1. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

    Directory of Open Access Journals (Sweden)

    James M Fox

    2016-03-01

    Full Text Available Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1 infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1, HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC of asymptomatic carriers (ACs and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP or adult T cell leukaemia/lymphoma (ATLL. 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.

  2. Oncogenic Viral Prevalence in Invasive Vulvar Cancer Specimens from HIV Positive and Negative Women in Botswana

    Science.gov (United States)

    Tesfalul, Martha; Simbiri, Kenneth; Wheat, Chikoti M.; Motsepe, Didintle; Goldbach, Hayley; Armstrong, Kathleen; Hudson, Kathryn; Kayembe, Mukendi K.; Robertson, Erle; Kovarik, Carrie

    2014-01-01

    Objective The primary aim of this study is to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with Human Immunodeficiency Virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world. Methods/materials A cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) viral testing were done for Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV) strains, and Kaposi's Sarcoma Herpesvirus (KSHV), and PCR viral testing alone was done for John Cunningham Virus (JCV). Results HPV prevalence by PCR was 100% (39/39 35/35) among tested samples. HPV16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). KSHV prevalence by PCR had a significant association with HIV status (p = 0.013), but not by IHC (p = 0.650). Conclusions The high burden of HPV, specifically HPV16, in VSCC in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses KSHV and EBV were also more prevalent in our study population though their potential role in VSCC pathology is unclear. PMID:24651632

  3. Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication.

    Directory of Open Access Journals (Sweden)

    Masha Sorin

    2009-06-01

    Full Text Available HIV-1 integrase (IN is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD, a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1 virions in an HIV-1 IN-dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1(H141A was utilized. Incorporation of HDAC1(H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1(H141A decreased the infectivity of HIV-1 (but not SIV virions. The block in infectivity due to virion-associated HDAC1(H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post

  4. Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk.

  5. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections.

    Directory of Open Access Journals (Sweden)

    Raphaël Gaudin

    Full Text Available During HIV pathogenesis, infected macrophages behave as "viral reservoirs" that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs. The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.

  6. Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda

    NARCIS (Netherlands)

    Balinda, Sheila N.; Ondoa, Pascale; Obuku, Ekwaro A.; Kliphuis, Aletta; Egau, Isaac; Bronze, Michelle; Kasambula, Lordwin; Schuurman, Rob; Spieker, Nicole; Rinke de Wit, Tobias F.; Kityo, Cissy

    2016-01-01

    WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing

  7. Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert.

    Science.gov (United States)

    Avidor, Boaz; Matus, Natalia; Girshengorn, Shirley; Achsanov, Svetlana; Gielman, Simona; Zeldis, Irene; Schweitzer, Inbal; Adler, Amos; Turner, Dan

    2017-08-01

    HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. A total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. There was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5' long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. This study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1.

    Science.gov (United States)

    Monde, Kazuaki; Contreras-Galindo, Rafael; Kaplan, Mark H; Markovitz, David M; Ono, Akira

    2012-10-01

    Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON) Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON) Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

  9. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Astvad, Karen; Ladelund, Steen

    2012-01-01

    OBJECTIVE: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis....... RESULTS: We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality......) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have...

  10. Viruses & kidney disease: beyond HIV

    Science.gov (United States)

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B.

    2008-01-01

    HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA. PMID:19013331

  11. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

    Directory of Open Access Journals (Sweden)

    Katja Pfafferott

    2011-02-01

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  12. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses t...

  13. HIV restriction by APOBEC3 in humanized mice.

    Directory of Open Access Journals (Sweden)

    John F Krisko

    2013-03-01

    Full Text Available Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3 family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV, Hepatitis B virus (HBV, Human Papilloma virus (HPV, and Human T Cell Leukemia virus (HTLV. The best characterized members of this family are APOBEC3G (A3G and APOBEC3F (A3F and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif. Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.

  14. Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jaffar, Shabbar; Van der Loeff, Maarten Schim; Eugen-Olsen, Jesper

    2005-01-01

    We investigated the association between beta2-microglobulin, neopterin, serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), CD4 count, and plasma viremia with survival in 133 HIV-2-infected villagers and 160 controls living in rural Guinea-Bissau. Subjects were recruited......%, and plasma viral load were associated independently with survival in multivariate analyses. Neopterin and suPAR did not reach statistical significance. These findings suggest that immune activation is central to the pathogenesis of HIV. They also have important implications for resource-poor settings where...

  15. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-05-17

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should

  16. Association of a 3' untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women.

    Science.gov (United States)

    Kuniholm, Mark H; Liang, Hua; Anastos, Kathryn; Gustafson, Deborah; Kassaye, Seble; Nowicki, Marek; Sha, Beverly E; Pawlowski, Emilia J; Gange, Stephen J; Aouizerat, Bradley E; Pushkarsky, Tatiana; Bukrinsky, Michael I; Prasad, Vinayaka R

    2017-11-28

    To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

  17. Plasma viraemia in HIV-positive pregnant women entering antenatal care in South Africa

    Science.gov (United States)

    Myer, Landon; Phillips, Tamsin K; Hsiao, Nei-Yuan; Zerbe, Allison; Petro, Gregory; Bekker, Linda-Gail; McIntyre, James A; Abrams, Elaine J

    2015-01-01

    Introduction Plasma HIV viral load (VL) is the principle determinant of mother-to-child HIV transmission (MTCT), yet there are few data on VL in populations of pregnant women in sub-Saharan Africa. We examined the distribution and determinants of VL in HIV-positive women seeking antenatal care (ANC) in Cape Town, South Africa. Methods Consecutive HIV-positive pregnant women making their first antenatal clinic visit were recruited into a cross-sectional study of viraemia in pregnancy, including a brief questionnaire and specimens for VL testing and CD4 cell enumeration. Results & discussion Overall 5551 pregnant women sought ANC during the study period, of whom 1839 (33%) were HIV positive and 1521 (85%) were included. Approximately two-thirds of HIV-positive women in the sample (n=947) were not on antiretrovirals at the time of the first ANC visit, and the remainder (38%, n=574) had initiated antiretroviral therapy (ART) prior to conception. For women not on ART, the median VL was 3.98 log10 copies/mL; in this group, the sensitivity of CD4 cell counts ≤350 cells/µL in detecting VL>10,000 copies/mL was 64% and this increased to 78% with a CD4 threshold of ≤500 cells/µL. Among women on ART, 78% had VL1000 copies/mL at the time of their ANC visit. Conclusions VL >10,000 copies/mL was commonly observed in women not on ART with CD4 cell counts >350 cells/µL, suggesting that CD4 cell counts may not be adequately sensitive in identifying women at greatest risk of MTCT. A large proportion of women entering ANC initiated ART before conception, and in this group more than 10% had VL>1000 copies/mL despite ART use. VL monitoring during pregnancy may help to identify pregnancies that require additional clinical attention to minimize MTCT risk and improve maternal and child health outcomes. PMID:26154734

  18. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-09-03

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general

  19. Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics

    Science.gov (United States)

    Lythgoe, Katrina A.; Blanquart, François

    2016-01-01

    The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation. PMID:27706164

  20. Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Mwila Mulubwa

    2016-07-01

    Objective: To investigate the correlation between plasma tenofovir (TFV concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART.These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30 on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR, creatinine clearance (CrCl, serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001 in HIV-infected women. In the adjusted (weight analysis, eGFR (p = 0.038,CrCl (p = 0.032 and albuminuria (p = 0.048 were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001 and CrCl (p = 0.008 increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

  1. Plasma fractionation issues.

    Science.gov (United States)

    Farrugia, Albert; Evers, Theo; Falcou, Pierre-Francois; Burnouf, Thierry; Amorim, Luiz; Thomas, Sylvia

    2009-04-01

    Procurement and processing of human plasma for fractionation of therapeutic proteins or biological medicines used in clinical practice is a multi-billion dollar international trade. Together the private sector and public sector (non-profit) provide large amounts of safe and effective therapeutic plasma proteins needed worldwide. The principal therapeutic proteins produced by the dichotomous industry include gamma globulins or immunoglobulins (including pathogen-specific hyperimmune globulins, such as hepatitis B immune globulins) albumin, factor VIII and Factor IX concentrates. Viral inactivation, principally by solvent detergent and other processes, has proven highly effective in preventing transmission of enveloped viruses, viz. HBV, HIV, and HCV.

  2. Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication

    Directory of Open Access Journals (Sweden)

    Belhumeur Pierre

    2008-11-01

    Full Text Available Abstract Background HIV-1 integrase (IN is a key viral enzymatic molecule required for the integration of the viral cDNA into the genome. Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. Interestingly, previous studies have demonstrated that the expression of HIV-1 IN induces the lethal phenotype in some strains of Saccharomyces cerevisiae. In this study, we performed mutagenic analyses of the C-terminal region of the catalytic core domain of HIV-1 IN in order to delineate the critical amino acid(s and/or motif(s required for the induction of the lethal phenotype in the yeast strain HP16, and to further elucidate the molecular mechanism which causes this phenotype. Results Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. Conclusion Overall, this study demonstrates that three mutations located in the C-terminal region of the catalytic core domain of HIV-1 IN inhibit the IN-induced lethal phenotype in yeast by inhibiting the binding of IN to the host chromatin. These results demonstrate that the C-terminal region of the catalytic core domain of HIV-1 IN is important for binding to host chromatin and is crucial for both viral replication and the promotion of

  3. HIV sexual transmission risks in the context of clinical care: a prospective study of behavioural correlates of HIV suppression in a community sample, Atlanta, GA, USA.

    Science.gov (United States)

    Kalichman, Seth C; Cherry, Chauncey; Kalichman, Moira O; Washington, Christopher; Grebler, Tamar; Merely, Cindy; Welles, Brandi; Pellowski, Jennifer; Kegler, Christopher

    2015-01-01

    Antiretroviral therapy (ART) improves the health of people living with HIV and has the potential to reduce HIV infectiousness, thereby preventing HIV transmission. However, the success of ART for HIV prevention hinges on sustained ART adherence and avoiding sexually transmitted infections (STI). To determine the sexual behaviours and HIV transmission risks of individuals with suppressed and unsuppressed HIV replication (i.e., viral load). Assessed HIV sexual transmission risks among individuals with clinically determined suppressed and unsuppressed HIV. Participants were 760 men and 280 women living with HIV in Atlanta, GA, USA, who completed behavioural assessments, 28-daily prospective sexual behaviour diaries, one-month prospective unannounced pill counts for ART adherence, urine screening for illicit drug use and medical record chart abstraction for HIV viral load. Individuals with unsuppressed HIV demonstrated a constellation of behavioural risks for transmitting HIV to uninfected sex partners that included symptoms of STI and substance use. In addition, 15% of participants with suppressed HIV had recent STI symptoms/diagnoses, indicating significant risks for sexual infectiousness despite their HIV suppression in blood plasma. Overall, 38% of participants were at risk for elevated sexual infectiousness and just as many engaged in unprotected sexual intercourse with non-HIV-infected partners. Implementation strategies for using HIV treatments as HIV prevention requires enhanced behavioural interventions that extend beyond ART to address substance use and sexual health that will otherwise undermine the potential preventive impact of early ART.

  4. Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children.

    Science.gov (United States)

    Moholisa, Retsilisitsoe R; Schomaker, Michael; Kuhn, Louise; Castel, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Strehlau, Renate; Patel, Faeezah; Pinillos, Francoise; Abrams, Elaine J; Maartens, Gary; McIlleron, Helen

    2016-12-01

    Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long-term viral suppression have not been adequately defined in children. We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy. After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) RESULTS:: At randomization, the median (interquartile range) age, CD4 T-Lymphocyte percentage, weight-for-age and weight-for-height z scores were 19 (16-24) months, 29% (23-37), -0.6 (-1.3 to 0.2) and -3.2 (-4.1 to -2.1), respectively. The proportion of children with viral load 51-400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1 versus ≥1 mg/L [adjusted hazard ratio 0.62 (95% confidence interval, 0.40-0.94)] and for children with viral loads 51-400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia. Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1 mg/L of lopinavir to ensure sustained viral suppression.

  5. EBV AND HHV-6 CIRCULATING SUBTYPES IN PEOPLE LIVING WITH HIV IN BURKINA FASO, IMPACT ON CD4 T CELL COUNT AND HIV VIRAL LOAD

    Directory of Open Access Journals (Sweden)

    Lassina TRAORE

    2017-09-01

    Full Text Available Epstein Barr Virus (EBV and Human Herpes Virus 6 (HHV-6 are responsible for severe diseases, particularly in immunocompromised persons. There are poor data on the infection with these opportunistic viruses in Burkina Faso. The purpose of this study is to characterize EBV and HHV-6 subtypes and to assess their impact on CD4 T cell count, HIV-1 viral load and antiretroviral treatment in people living with HIV-1. The study population consisted of 238 HIV-positive patients with information on CD4 count, HIV-1 viral load and HAART. Venous blood samples collected on EDTA tubes were used for EBV and HHV-6 Real Time PCR subtyping. An infection rate of 6.7% (16/238 and 7.1% (17/238 were found respectively for EBV and HHV-6 in the present study. Among EBV infections, similar prevalences were noted for both subtypes (3.9% [9/238] for EBV-1 vs 4.6% [11/238] for EBV-2 with 2.1% (5/238 of co-infection. HHV-6A infection represented 6.3% (15/238 of the study population against 5.0% (12/238 for HHV-6B. . EBV-2 infection was significantly higher in patients with CD4 count ≥ 500 compared to those with CD4 count less than 500 cells (1.65% vs 8.56%, p = 0,011. The prevalence of EBV and HHV-6 infections were almost similar in HAART-naive and HAART-experienced patients. The present study provides information on the prevalence of EBV and HHV-6 subtypes in people living with HIV-1 in Burkina Faso. The study also suggests that HAART treatment has no effect on infection with these opportunistic viruses in people living with HIV-1.

  6. Comparative Analysis of Gender Differences in the HIV-1 Infection Dynamics

    Science.gov (United States)

    Ballesteros, P.; Estrada, J. L.; Barriga, G.; Molinar, F.; Hernández, M. C.; Huerta, L.; Cocho, G.; Villarreal, C.

    2006-09-01

    We have performed a retrospective study of the HIV-1 viral load and CD4 T-cell counts in blood plasma of more than 3000 Mexican patients. We found that women had consistently lower viral loads than men for CD4 T-cell counts higher than 50 cells/μL and higher viral loads when CD4 T-cell counts were at most 50 cells/μL. Our results show the same pattern as the one reported in studies performed in European and North American populations. We present theoretical predictions of viral load dynamics during highly active antiretroviral therapy taking into account gender differences.

  7. Four-tiered π interaction at the dimeric interface of HIV-1 integrase critical for DNA integration and viral infectivity

    International Nuclear Information System (INIS)

    Al-Mawsawi, Laith Q.; Hombrouck, Anneleen; Dayam, Raveendra; Debyser, Zeger; Neamati, Nouri

    2008-01-01

    HIV-1 integrase (IN) is an essential enzyme for viral infection. Here, we report an extensive π electron orbital interaction between four amino acids, W132, M178, F181 and F185, located at the dimeric interface of IN that is critical for the strand transfer activity alone. Catalysis of nine different mutant IN proteins at these positions were evaluated. Whereas the 3'-processing activity is predominantly strong, the strand transfer activity of each enzyme was completely dependent on an intact π electron orbital interaction at the dimeric interface. Four representative IN mutants were constructed in the context of the infectious NL4.3 HIV-1 viral clone. Whereas viruses with an intact π electron orbital interaction at the IN dimeric interface replicated comparable to wild type, viruses containing an abolished π interaction were non-infectious. Q-PCR analysis of viral DNA forms during viral replication revealed pleiotropic effects of most mutations. We hypothesize that the π interaction is a critical contact point for the assembly of functional IN multimeric complexes, and that IN multimerization is required for a functional pre-integration complex. The rational design of small molecule inhibitors targeting the disruption of this π-π interaction should lead to powerful anti-retroviral drugs

  8. Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa.

    Science.gov (United States)

    Sigaloff, Kim C E; Hamers, Raph L; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Ive, Prudence; Botes, Mariette E; Mandaliya, Kishor; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; van Vugt, Michèle; de Wit, Tobias F Rinke

    2011-09-01

    This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated. Cross-sectional analysis of adults switching ART regimens at 13 clinical sites in 6 African countries was performed. Two types of failure identification were compared: diagnosis of clinicoimmunological failure without viral load testing (CIF only) or CIF with local targeted viral load testing (targeted VL). After study enrollment, reference HIV RNA and genotype were determined retrospectively. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI cross-resistance (≥2 TAMs or Q151M or K65R/K70E). Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA <1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P < 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising ≥2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use. Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa.

  9. Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

    Science.gov (United States)

    Li, Xiaolin; Wu, Tong; Jiang, Yongjun; Zhang, Zining; Han, Xiaoxu; Geng, Wenqing; Ding, Haibo; Kang, Jing; Wang, Qi; Shang, Hong

    2018-05-16

    The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc.

    Science.gov (United States)

    Chaillon, Antoine; Gianella, Sara; Lada, Steven M; Perez-Santiago, Josué; Jordan, Parris; Ignacio, Caroline; Karris, Maile; Richman, Douglas D; Mehta, Sanjay R; Little, Susan J; Wertheim, Joel O; Smith, Davey M

    2018-02-01

    Residual viremia is common during antiretroviral therapy (ART) and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial and monitored for a median of 107 weeks. Participants started ART with ( n = 9) or without ( n = 9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR. Deep sequencing of C2-V3 env , gag , and pol (454 Roche) was performed on longitudinally collected plasma and peripheral blood mononuclear cell (PBMC) samples while on ART. Sequence data were analyzed for evidence of evolution by (i) molecular diversity analysis, (ii) nonparametric test for panmixia, and (iii) tip date randomization within a Bayesian framework. There was a longitudinal decay of HIV DNA after initiation of ART with no difference between MVC intensification groups (-0.08 ± 0.01 versus -0.09 ± 0.01 log 10 copies/week in MVC + versus MVC - groups; P = 0.62). All participants had low-level residual viremia (median, 2.8 RNA copies/ml). Across participants, medians of 56 (interquartile range [IQR], 36 to 74), 29 (IQR, 25 to 35), and 40 (IQR, 31 to 54) haplotypes were generated for env , gag , and pol regions, respectively. There was no clear evidence of viral evolution during ART and no difference in viral diversity or population structure from individuals with or without MVC intensification. Further efforts focusing on elucidating the mechanism(s) of viral persistence in various compartments using recent sequencing technologies are still needed, and potential low-level viral replication should always be considered in cure strategies. IMPORTANCE Residual viremia is common among HIV-infected people on ART. It remains controversial if this viremia is a consequence of propagating

  11. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  12. TOXOPLASMA AND VIRAL ANTIBODIES AMONG HIV PATIENTS AND INMATES IN CENTRAL JAVA, INDONESIA.

    Science.gov (United States)

    Sari, Yulia; Haryati, Sri; Raharjo, Irvan; Prasetyo, Afiono Agung

    2015-11-01

    In Indonesia, Toxoplasma and its associations with blood-borne viruses have been poorly studied. In order to study the association between anti-Toxoplasma antibodies and blood-borne viral antibodies, blood samples from 497 participants (375 inmates from four prisons in Central Java, Indonesia and 122 HIV patients at a Voluntary Counseling and Testing Clinic in Surakarta, Indonesia) were tested for serological markers of Toxoplasma, human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and human T-lymphotropic virus types I and II (HTLV-1/2). Anti-Toxoplasma IgG and IgM positivity rates were 41.6% and 3.6%, respectively. One point two percent of participants was positive for both anti-Toxoplasma IgG and IgM antibodies. Sixteen point five percent, 11.3%, 2.6% and 2.8% of participants were positive for anti- Toxoplasma IgG combined with anti-HCV antibodies, anti-Toxoplasma IgG combined with anti-HIV antibodies, anti-Toxoplasma IgM combined with anti-HIV antibodes and anti-Toxoplasma IgG combined with both anti-HIV and anti-HCV antibodies, respectively. Anti-Toxoplasma IgM seropositivity was associated with anti-HIV (aOR = 4.3; 95% CI: 1.112-16.204, p = 0.034). Anti-Toxoplasma IgG antibodies were associated with anti-HCV (aOR = 2.8; 95% CI: 1.749-4.538, p < 0.001) and history of injection drug use (aOR = 3.1; 95% CI: 1.905-5.093, p < 0.001). In conclusion, we recommend patients with HIV, HCV infection and injection drug users should be screened for Toxoplasma infection in Indonesia.

  13. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    International Nuclear Information System (INIS)

    Janas, Alicia M.; Dong, Chunsheng; Wang Jianhua; Wu Li

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection

  14. CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV.

    Science.gov (United States)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Gitte; Pedersen, Court; Obel, Niels; Gerstoft, Jan

    2013-07-01

    The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer. Patients with human immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable. We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2-5.4]). CD4 counts dropped from a median of 492 cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate ratio, 11.7 [95% CI, 3.6-37.4] and 13.7 [95% CI, 4.3-43.6], respectively, and mortality rate ratio 4.3 [95% CI, 1.1-17.6]). A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer, and death among virally suppressed HIV patients.

  15. Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

    Science.gov (United States)

    Fox, Julie; Brady, Michael; Alexander, Hannah; Davies, Olubanke; Robinson, Nicola; Pace, Mathew; Else, Laura; Cason, John; Khoo, Saye; Back, David; Fidler, Sarah; Frater, John

    2016-03-01

    The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

  16. Minimal residual HIV viremia: verification of the Abbott Real-Time HIV-1 assay sensitivity

    Directory of Open Access Journals (Sweden)

    Alessandra Amendola

    2010-06-01

    Full Text Available Introduction: In the HIV-1 infection, the increase in number of CD4 T lymphocytes and the viral load decline are the main indicators of the effectiveness of antiretroviral therapy. On average, 85% of patients receiving effective treatment has a persistent suppression of plasma viral load below the detection limit (<50 copies/mL of clinically used viral load assays, regardless of treatment regimen in use. It is known, however, that, even when viremia is reduced below the sensitivity limit of current diagnostic assays, the virus persists in “reservoirs” and traces of free virions can be detected in plasma.There is a considerable interest to investigate the clinical significance of residual viremia. Advances in molecular diagnostics allows nowadays to couple a wide dynamic range to a high sensitivity.The Abbott Real-time HIV-1 test is linear from 40 to 107 copies/mL and provides, below 40 copies/mL, additional information such as “<40cp/mL, target detected” or “target not detected”. The HIV-1 detection is verified by the max-Ratio algorithm software.We assessed the test sensitivity when the qualitative response is considered as well. Methods: A ‘probit’ analysis was performed using dilutions of the HIV-1 RNA Working Reagent 1 for NAT assays (NIBSC code: 99/634, defined in IU/mL and different from that used by the manufacturer (VQA,Virology Quality Assurance Laboratory of the AIDS Clinical Trial Group for standardization and definition of performances.The sample input volume (0.6 mL was the same used in clinical routine. A total of 196 replicates at concentrations decreasing from 120 to 5 copies/mL, in three different sessions, have been tested.The ‘probit’ analysis (binomial dose-response model, 95% “hit-rate” has been carried out on the SAS 9.1.3 software package. Results: The sensitivity of the “<40cp/mL, target detected” response was equal to 28,76 copies/mL, with 95% confidence limits between 22,19 and 52,27 copies

  17. [Microbiological diagnosis of HIV infection].

    Science.gov (United States)

    López-Bernaldo de Quirós, Juan Carlos; Delgado, Rafael; García, Federico; Eiros, José M; Ortiz de Lejarazu, Raúl

    2007-12-01

    Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

  18. Clinical significance of measurement of changes of serum NSE and plasma NPY levels after treatment in pediatric patients with viral encephalitis

    International Nuclear Information System (INIS)

    Jin Bo; Zheng Guo

    2007-01-01

    Objective: To explore the significance ef changes of serum NSE and plasma NPY levels after treatment in pediatric patients with viral encephalitis. Methods: Serum NSE and plasma NPY levels were measured with RIA in 32 pediatric patients with viral encephalitis both before and after treatment as well as in 30 controls. Results: Before treatment, in the patients, the serum NSE and plasma NPY levels were significantly higher than those in controls (P<0.01). After 1 month's treatment the levels dropped markedly but still remained significantly higher than those in controls (P<0.05). Conclusion: Serum NSE and plasma NPY levels changes were closely related to the progress of viral encephalitis. (authors)

  19. Viruses and kidney disease: beyond HIV.

    Science.gov (United States)

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B

    2008-11-01

    Human immunodeficiency virus (HIV)-infected patients may acquire new viral co-infections; they also may experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections owing to immunodeficiency or risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.

  20. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.  Created: 6/9/2011 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 6/9/2011.

  1. Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

    Directory of Open Access Journals (Sweden)

    V. N. Timchenko

    2016-01-01

    Full Text Available The study included 338 HIV-infected children (B-23 and 350 children with perinatal contact HIV infection (R-75, consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5% diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

  2. HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    Science.gov (United States)

    Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

    2018-04-01

    Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

  3. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Directory of Open Access Journals (Sweden)

    Jim Todd

    Full Text Available To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1 57 women at 70 clinic visits with clinical genital herpes; (2 39 of the same women at 46 clinic visits when asymptomatic; (3 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL, herpetic lesions, HSV shedding and other factors were examined.Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03. In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001 and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001 but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27.HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  4. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

    Science.gov (United States)

    Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

    2013-10-24

    The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus

  5. Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.

    Science.gov (United States)

    Clarridge, Katherine E; Blazkova, Jana; Einkauf, Kevin; Petrone, Mary; Refsland, Eric W; Justement, J Shawn; Shi, Victoria; Huiting, Erin D; Seamon, Catherine A; Lee, Guinevere Q; Yu, Xu G; Moir, Susan; Sneller, Michael C; Lichterfeld, Mathias; Chun, Tae-Wook

    2018-01-01

    Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6-12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies.

  6. Workup of Human Blood Samples for Deep Sequencing of HIV-1 Genomes

    NARCIS (Netherlands)

    Cornelissen, Marion; Gall, Astrid; van der Kuyl, Antoinette; Wymant, Chris; Blanquart, François; Fraser, Christophe; Berkhout, Ben

    2018-01-01

    We describe a detailed protocol for the manual workup of blood (plasma/serum) samples from individuals infected with the human immunodeficiency virus type 1 (HIV-1) for deep sequence analysis of the viral genome. The study optimizing the assay was performed in the context of the BEEHIVE (Bridging

  7. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study

    NARCIS (Netherlands)

    Montaner, J. S.; Reiss, P.; Cooper, D.; Vella, S.; Harris, M.; Conway, B.; Wainberg, M. A.; Smith, D.; Robinson, P.; Hall, D.; Myers, M.; Lange, J. M.

    1998-01-01

    CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving

  8. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity.

    Directory of Open Access Journals (Sweden)

    Rui Jia

    Full Text Available The interferon-inducible transmembrane (IFITM proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1 strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3 is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117-125, which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117-125 mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117-125 to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117-125, mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.

  9. Viral load and genomic integration of HPV 16 in cervical samples from HIV-1-infected and uninfected women in Burkina Faso.

    Science.gov (United States)

    Rousseau, Marie-Noelle Didelot; Costes, Valérie; Konate, Issouf; Nagot, Nicolas; Foulongne, Vincent; Ouedraogo, Abdoulaye; Van de Perre, Philippe; Mayaud, Philippe; Segondy, Michel

    2007-06-01

    The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV 16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and cervical cytology were studied among women enrolled in a cohort of female sex workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV 16 viral load in cervical samples was determined by real-time PCR. Integration ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers. Integrated HPV16 viral load was defined as the product of HPV 16 viral load by the integration ratio. High HPV 16 viral load and high integration ratio were more frequent among women with squamous intraepithelial lesions compared with women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among women with high-grade squamous intraepithelial lesions compared with women without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs. 11%, respectively). High HPV 16 DNA load, but not high integration ratio, was also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%, respectively). The absence of statistical significance of these differences might be explained by the small study sample size. High-integrated HPV 16 DNA load was significantly associated with the presence of high-grade squamous intraepithelial lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may be considered as a useful marker of high-grade cervical lesions in HPV 16-infected women. (c) 2007 Wiley-Liss, Inc.

  10. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.

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    Weijun Zhu

    Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

  11. Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

    Science.gov (United States)

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

    2017-05-01

    In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

  12. Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV?

    Directory of Open Access Journals (Sweden)

    Sophia Pathai

    Full Text Available HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa.Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye.The median age was 40 years (IQR: 35-48 years. Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART (median duration, 58 months, their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15. Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07. Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm 6 years, p-trend = 0.02, and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05. HIV-related venular changes were not detected.Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.

  13. The natural history of HIV infection

    DEFF Research Database (Denmark)

    Sabin, C.A.; Lundgren, J.D.

    2013-01-01

    PURPOSE OF REVIEW: To review recent published literature around three areas: long-term nonprogression/viral control; predictors of viral load set point/disease progression; and the potential impact of antiretroviral therapy (ART) in early HIV infection. RECENT FINDINGS: The natural course...... of untreated HIV infection varies widely with some HIV-positive individuals able to maintain high CD4 cell counts and/or suppressed viral load in the absence of ART. Although similar, the underlying mechanistic processes leading to long-term nonprogression and viral control are likely to differ. Concerted...... the immunological deterioration which would otherwise be seen in untreated HIV infection, recent studies do not address the longer term clinical benefits of ART at this very early stage. SUMMARY: A better understanding of the relative influences of viral, host, and environmental factors on the natural course of HIV...

  14. Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha; Pai, Madhukar

    2018-04-01

    Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation ( n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation ( n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics ( n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. Copyright © 2018 Nash et al.

  15. Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy

    Directory of Open Access Journals (Sweden)

    Carmen D Zorrilla

    2009-12-01

    Full Text Available Carmen D Zorrilla, Vivian Tamayo-AgraitDepartment of Obstetrics and Gynecology, University of Puerto Rico School of Medicine, Maternal Infant Studies Center (CEMI, San Juan, Puerto RicoAbstract: Over the past decade, significant advances have been made in the treatment of HIV-1 infection using both pharmacologic and nonpharmacologic strategies to prevent mother-to-child transmission (MTCT. Optimal prevention of the MTCT of HIV requires antiretroviral drugs (ARV during pregnancy, during labor, and to the infant. ARVs reduce viral replication, lowering maternal plasma viral load and thus the likelihood of MTCT. Postexposure prophylaxis of ARV agents in newborns protect against infection following potential exposure to maternal HIV during birth. In general, the choice of an ARV for treatment of HIV-infected women during pregnancy is complicated by the need to consider the effectiveness of the therapy for the maternal disease as well as the teratogenic or teratotoxic potential of these drugs. Clinicians managing HIV in pregnancy need to discuss the potential risks and benefits of available therapy options so that mothers can make informed decisions in choosing the best treatment regimen for themselves and for their children.Keywords: HIV, pregnancy, acquired immunodeficiency syndrome, antiretroviral agents

  16. A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children

    Science.gov (United States)

    Persaud, Deborah; Pierson, Theodore; Ruff, Christian; Finzi, Diana; Chadwick, Karen R.; Margolick, Joseph B.; Ruff, Andrea; Hutton, Nancy; Ray, Stuart; Siliciano, Robert F.

    2000-01-01

    HIV-1 persists in a latent state in resting CD4+ T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4+ T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4+ T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1–3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4+ T cells will be a major obstacle to HIV-1 eradication in children. PMID:10749578

  17. Neurologic signs and symptoms frequently manifest in acute HIV infection

    Science.gov (United States)

    Fletcher, James L.K.; Valcour, Victor; Kroon, Eugène; Ananworanich, Jintanat; Intasan, Jintana; Lerdlum, Sukalaya; Narvid, Jared; Pothisri, Mantana; Allen, Isabel; Krebs, Shelly J.; Slike, Bonnie; Prueksakaew, Peeriya; Jagodzinski, Linda L.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Spudich, Serena

    2016-01-01

    Objective: To determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre–antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART). Methods: Participants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained. Results: Median estimated HIV infection duration was 19 days (range 3–56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006). Conclusions: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV. PMID:27287217

  18. Vinblastine, rituximab and HAART, treatment of an HIV -positive patient with multicentric Castleman's disease

    NARCIS (Netherlands)

    van Aalderen, M. C.; Brinkman, K.; van den Berk, G. E. L.; Terpstra, W. E.

    2010-01-01

    An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lymphadenopathy and splenomegaly. An FDG-PET-scan-guided lymph node biopsy revealed the characteristic histological features of the plasma cell variant of Castleman's disease. A high HHV-8 viral load was

  19. A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

    Science.gov (United States)

    Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

    2010-12-01

    Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

  20. Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

    Science.gov (United States)

    Miller, Tracie L.; Borkowsky, William; DiMeglio, Linda A.; Dooley, Laurie; Geffner, Mitchell E.; Hazra, Rohan; McFarland, Elizabeth J.; Mendez, Armando J.; Patel, Kunjal; Siberry, George K.; Van Dyke, Russell B.; Worrell, Carol J.; Jacobson, Denise L.

    2011-01-01

    Objectives Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. Design Prospective cohort study Methods Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. Results The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). Conclusions HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication. PMID:22136114

  1. Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    Matee Mecky

    2008-12-01

    Full Text Available Abstract Background Tanzania is currently scaling-up access to anti-retro viral therapy (ART to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country. Methods A cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged ≥18 years presenting at the HIV care and treatment clinic (CTC of the Muhimbili National Hospital (MNH. The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA. Results The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%, while that of HAV and HBV was detected in two subjects (0.8%. None of the patients had all the three hepatitis viruses. Most patients (81.1% with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively. Conclusion There is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.

  2. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  3. Validation of Simultaneous Quantitative Method of HIV Protease Inhibitors Atazanavir, Darunavir and Ritonavir in Human Plasma by UPLC-MS/MS

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    Tulsidas Mishra

    2014-01-01

    Full Text Available Objectives. HIV protease inhibitors are used in the treatment of patients suffering from AIDS and they act at the final stage of viral replication by interfering with the HIV protease enzyme. The paper describes a selective, sensitive, and robust method for simultaneous determination of three protease inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra performance liquid chromatography-tandem mass spectrometry. Materials and Methods. The sample pretreatment consisted of solid phase extraction of analytes and their deuterated analogs as internal standards from 50 μL human plasma. Chromatographic separation of analytes was performed on Waters Acquity UPLC C18 (50 × 2.1 mm, 1.7 μm column under gradient conditions using 10 mM ammonium formate, pH 4.0, and acetonitrile as the mobile phase. Results. The method was established over a concentration range of 5.0–6000 ng/mL for atazanavir, 5.0–5000 ng/mL for darunavir and 1.0–500 ng/mL for ritonavir. Accuracy, precision, matrix effect, recovery, and stability of the analytes were evaluated as per US FDA guidelines. Conclusions. The efficiency of sample preparation, short analysis time, and high selectivity permit simultaneous estimation of these inhibitors. The validated method can be useful in determining plasma concentration of these protease inhibitors for therapeutic drug monitoring and in high throughput clinical studies.

  4. Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.

    Directory of Open Access Journals (Sweden)

    Terrence M Dobrowsky

    2010-07-01

    Full Text Available The fusion of the human immunodeficiency virus type 1 (HIV-1 with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection.

  5. Higher risk sexual behaviour is associated with unawareness of HIV-positivity and lack of viral suppression - implications for Treatment as Prevention.

    Science.gov (United States)

    Huerga, Helena; Venables, Emilie; Ben-Farhat, Jihane; van Cutsem, Gilles; Ellman, Tom; Kenyon, Chris

    2017-11-23

    Efficacy of Treatment as Prevention Strategy depends on a variety of factors including individuals' likelihood to test and initiate treatment, viral load and sexual behaviour. We tested the hypothesis that people with higher risk sexual behaviour are less likely to know their HIV-positive status and be virologically suppressed. A cross-sectional population-based survey of individuals aged 15-59 years old was conducted in 2013 in KwaZulu-Natal, South Africa. A two-stage cluster probability sampling was used. After adjustment for age and sex, lack of awareness of HIV-positivity was strongly associated with having more than one sexual partner in the preceding year (aOR: 2.1, 95%CI: 1.5-3.1). Inconsistent condom use was more common in individuals with more than one sexual partner (aOR: 16.6, 95%CI: 7.6-36.7) and those unaware (aOR: 3.7, 95%CI: 2.6-5.4). Among people aware of their HIV-positivity, higher risk sexual behaviour was associated with lack of viral suppression (aOR: 2.2, 95%CI: 1.1-4.5). Risky sexual behaviour seems associated with factors linked to poor health-seeking behaviour which may have negative implications for HIV testing and Treatment as Prevention. Innovative strategies, driven by improved epidemiological and anthropological understanding, are needed to enable comprehensive approaches to HIV prevention.

  6. HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand.

    Science.gov (United States)

    Forhan, S E; Dunne, E F; Sternberg, M R; Whitehead, S J; Leelawiwat, W; Thepamnuay, S; Chen, C; Evans-Strickfaden, Tt; McNicholl, J M; Markowitz, L E

    2012-08-01

    We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P genital sampling, and inclusion of genital sites other than the cervix.

  7. Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing on Linkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The CASCADE Randomized Clinical Trial.

    Science.gov (United States)

    Labhardt, Niklaus D; Ringera, Isaac; Lejone, Thabo I; Klimkait, Thomas; Muhairwe, Josephine; Amstutz, Alain; Glass, Tracy R

    2018-03-20

    Home-based HIV testing is a frequently used strategy to increase awareness of HIV status in sub-Saharan Africa. However, with referral to health facilities, less than half of those who test HIV positive link to care and initiate antiretroviral therapy (ART). To determine whether offering same-day home-based ART to patients with HIV improves linkage to care and viral suppression in a rural, high-prevalence setting in sub-Saharan Africa. Open-label, 2-group, randomized clinical trial (February 22, 2016-September 17, 2017), involving 6 health care facilities in northern Lesotho. During home-based HIV testing in 6655 households from 60 rural villages and 17 urban areas, 278 individuals aged 18 years or older who tested HIV positive and were ART naive from 268 households consented and enrolled. Individuals from the same household were randomized into the same group. Participants were randomly assigned to be offered same-day home-based ART initiation (n = 138) and subsequent follow-up intervals of 1.5, 3, 6, 9, and 12 months after treatment initiation at the health facility or to receive usual care (n = 140) with referral to the nearest health facility for preparatory counseling followed by ART initiation and monthly follow-up visits thereafter. Primary end points were rates of linkage to care within 3 months (presenting at the health facility within 90 days after the home visit) and viral suppression at 12 months, defined as a viral load of less than 100 copies/mL from 11 through 14 months after enrollment. Among 278 randomized individuals (median age, 39 years [interquartile range, 28.0-52.0]; 180 women [65.7%]), 274 (98.6%) were included in the analysis (137 in the same-day group and 137 in the usual care group). In the same-day group, 134 (97.8%) indicated readiness to start ART that day and 2 (1.5%) within the next few days and were given a 1-month supply of ART. At 3 months, 68.6% (94) in same-day group vs 43.1% (59) in usual care group had linked to care

  8. A pilot study to evaluate the magnitude of association of the use of electronic personal health records with patient activation and empowerment in HIV-infected veterans

    Directory of Open Access Journals (Sweden)

    Pierre-Cédric B. Crouch

    2015-03-01

    Full Text Available The HITECH Act signed into law in 2009 requires hospitals to provide patients with electronic access to their health information through an electronic personal health record (ePHR in order to receive Medicare/Medicaid incentive payments. Little is known about who uses these systems or the impact these systems will have on patient outcomes in HIV care. The health care empowerment model provides rationale for the hypothesis that knowledge from an electronic personal health record can lead to greater patient empowerment resulting in improved outcomes. The objective was to determine the patient characteristics and patient activation, empowerment, satisfaction, knowledge of their CD4, Viral Loads, and antiretroviral medication, and medication adherence outcomes associated with electronic personal health record use in Veterans living with HIV at the San Francisco VA Medical Center. The participants included HIV-Infected Veterans receiving care in a low volume HIV-clinic at the San Francisco VA Medical Center, divided into two groups of users and non-users of electronic personal health records. The research was conducted using in-person surveys either online or on paper and data abstraction from medical records for current anti-retroviral therapy (ART, CD4 count, and plasma HIV-1 viral load. The measures included the Patient Activation Measure, Health Care Empowerment Inventory, ART adherence, provider satisfaction, current CD4 count, current plasma viral load, knowledge of current ART, knowledge of CD4 counts, and knowledge of viral load. In all, 40 participants were recruited. The use of electronic personal health records was associated with significantly higher levels of patient activation and levels of patient satisfaction for getting timely appointments, care, and information. ePHR was also associated with greater proportions of undetectable plasma HIV-1 viral loads, of knowledge of current CD4 count, and of knowledge of current viral load. The

  9. Stimulation of HIV-1-specific cytolytic T-lymphocytes facilitates elimination of latent viral reservoir after virus reactivation

    Science.gov (United States)

    Shan, Liang; Deng, Kai; Shroff, Neeta S.; Durand, Christine; Rabi, S. Alireza.; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B.; Blankson, Joel N.; Siliciano, Robert F.

    2012-01-01

    Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia. Life-long treatment is therefore required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T-cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4+ T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T-lymphocytes (CTL) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials. PMID:22406268

  10. Detection of HIV-1 p24 Gag in plasma by a nanoparticle-based bio-barcode-amplification method.

    Science.gov (United States)

    Kim, Eun-Young; Stanton, Jennifer; Korber, Bette T M; Krebs, Kendall; Bogdan, Derek; Kunstman, Kevin; Wu, Samuel; Phair, John P; Mirkin, Chad A; Wolinsky, Steven M

    2008-06-01

    Detection of HIV-1 in patients is limited by the sensitivity and selectivity of available tests. The nanotechnology-based bio-barcode-amplification method offers an innovative approach to detect specific HIV-1 antigens from diverse HIV-1 subtypes. We evaluated the efficacy of this protein-detection method in detecting HIV-1 in men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS). The method relies on magnetic microparticles with antibodies that specifically bind the HIV-1 p24 Gag protein and nanoparticles that are encoded with DNA and antibodies that can sandwich the target protein captured by the microparticle-bound antibodies. The aggregate sandwich structures are magnetically separated from solution, and treated to remove the conjugated barcode DNA. The DNA barcodes (hundreds per target) were identified by a nanoparticle-based detection method that does not rely on PCR. Of 112 plasma samples from HIV-1-infected subjects, 111 were positive for HIV-1 p24 Gag protein (range: 0.11-71.5 ng/ml of plasma) by the bio-barcode-amplification method. HIV-1 p24 Gag protein was detected in only 23 out of 112 men by the conventional ELISA. A total of 34 uninfected subjects were negative by both tests. Thus, the specificity of the bio-barcode-amplification method was 100% and the sensitivity 99%. The bio-barcode-amplification method detected HIV-1 p24 Gag protein in plasma from all study subjects with less than 200 CD4(+) T cells/microl of plasma (100%) and 19 out of 20 (95%) HIV-1-infected men who had less than 50 copies/ml of plasma of HIV-1 RNA. In a separate group of 60 diverse international isolates, representative of clades A, B, C and D and circulating recombinant forms CRF01_AE and CRF02_AG, the bio-barcode-amplification method identified the presence of virus correctly. The bio-barcode-amplification method was superior to the conventional ELISA assay for the detection of HIV-1 p24 Gag protein in plasma with a breadth of coverage for diverse

  11. Efficient neutralization of primary isolates by the plasma from HIV-1 infected Indian children.

    Science.gov (United States)

    Prakash, S S; Chaudhary, Alok Kumar; Lodha, Rakesh; Kabra, S K; Vajpayee, Madhu; Hazarika, Anjali; Bagga, Barun; Luthra, Kalpana

    2011-10-01

    We tested the plasma of 51 HIV-1-infected children (23 naïve and 28 ART treated) for neutralization against five primary isolates (PIs) generated from adult Indian HIV-1-infected patients. The plasma exhibited neutralization potential with significantly higher neutralizing antibody titers in ART-treated children than naïve children against three out of five PIs (pIndian children.

  12. Viral gene products and replication of the human immunodeficiency type 1 virus.

    Science.gov (United States)

    Morrow, C D; Park, J; Wakefield, J K

    1994-05-01

    The acquired immunodeficiency syndrome (AIDS) epidemic represents a modern-day plague that has not only resulted in a tragic loss of people from a wide spectrum of society but has reshaped our viewpoints regarding health care, the treatment of infectious diseases, and social issues regarding sexual behavior. There is little doubt now that the cause of the disease AIDS is a virus known as the human immunodeficiency virus (HIV). The HIV virus is a member of a large family of viruses termed retroviruses, which have as a hallmark the capacity to convert their RNA genome into a DNA form that then undergoes a process of integration into the host cell chromosome, followed by the expression of the viral genome and translation of viral proteins in the infected cell. This review describes the organization of the HIV-1 viral genome, the expression of viral proteins, as well as the functions of the accessory viral proteins in HIV replication. The replication of the viral genome is divided into two phases, the early phase and the late phase. The early phase consists of the interaction of the virus with the cell surface receptor (CD4 molecule in most cases), the uncoating and conversion of the viral RNA genome into a DNA form, and the integration into the host cell chromosome. The late phase consists of the expression of the viral proteins from the integrated viral genome, the translation of viral proteins, and the assembly and release of the virus. Points in the HIV-1 life cycle that are targets for therapeutic intervention are also discussed.

  13. D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.

    Directory of Open Access Journals (Sweden)

    Matthew S Freiberg

    Full Text Available The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6 at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002. This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03. Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

  14. Viruses & kidney disease: beyond HIV

    OpenAIRE

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B.

    2008-01-01

    HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and t...

  15. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation.

    Science.gov (United States)

    Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert

    2017-11-01

    This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

  16. National HIV/AIDS Strategy

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about the importance of the National HIV/AIDS Strategy and the work of CDC.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  17. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  18. Intrinsically disordered region of influenza A NP regulates viral genome packaging via interactions with viral RNA and host PI(4,5)P2.

    Science.gov (United States)

    Kakisaka, Michinori; Yamada, Kazunori; Yamaji-Hasegawa, Akiko; Kobayashi, Toshihide; Aida, Yoko

    2016-09-01

    To be incorporated into progeny virions, the viral genome must be transported to the inner leaflet of the plasma membrane (PM) and accumulate there. Some viruses utilize lipid components to assemble at the PM. For example, simian virus 40 (SV40) targets the ganglioside GM1 and human immunodeficiency virus type 1 (HIV-1) utilizes phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2]. Recent studies clearly indicate that Rab11-mediated recycling endosomes are required for influenza A virus (IAV) trafficking of vRNPs to the PM but it remains unclear how IAV vRNP localized or accumulate underneath the PM for viral genome incorporation into progeny virions. In this study, we found that the second intrinsically disordered region (IDR2) of NP regulates two binding steps involved in viral genome packaging. First, IDR2 facilitates NP oligomer binding to viral RNA to form vRNP. Secondly, vRNP assemble by interacting with PI(4,5)P2 at the PM via IDR2. These findings suggest that PI(4,5)P2 functions as the determinant of vRNP accumulation at the PM. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

    DEFF Research Database (Denmark)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm

    2016-01-01

    AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ...

  20. Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young Men Who Have Sex with Men and Transgender Women in Chicago: Implications for Epidemiology, Care, and Prevention.

    Science.gov (United States)

    Mustanski, Brian; Ryan, Daniel T; Remble, Thomas A; D'Aquila, Richard T; Newcomb, Michael E; Morgan, Ethan

    2018-04-10

    Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.

  1. Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

    Directory of Open Access Journals (Sweden)

    Wilke Claus O

    2008-01-01

    Full Text Available Abstract Background In the setting of highly active antiretroviral therapy (HAART, plasma levels of human immunodeficiency type-1 (HIV-1 rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.

  2. Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

    Science.gov (United States)

    Sedaghat, Ahmad R; Siliciano, Robert F; Wilke, Claus O

    2008-01-01

    Background In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir. PMID:18171475

  3. Effectiveness of semen washing to prevent HIV transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis

    Science.gov (United States)

    Zafer, Maryam; Horvath, Hacsi; Mmeje, Okeoma; van der Poel, Sheryl; Semprini, Augusto; Rutherford, George; Brown, Joelle

    2015-01-01

    Objective To evaluate the effectiveness of semen washing in HIV-discordant couples in which the male partner is infected Design Systematic review and meta-analysis Setting All countries Patient(s) Forty single-arm, open label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen Intervention(s) Semen washing followed by IUI, IVF, or IVF/ICSI Main outcome measure(s) Primary outcome: HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy Result(s) No HIV transmission occurred in 11,585 cycles of assisted reproduction using washed semen among 3,994 women (95% confidence interval [CI] = 0–0.0001). Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women following 2,863 cycles of assisted reproduction using washed semen (95%CI= 0–0.0006). Studies that measured HIV transmission to infants reported no cases of vertical transmission (0/1,026, 95% CI= 0–0.0029). Overall, 56.3% (2,357/4,184, 95%CI=54.8%–57.8%) of couples achieved a clinical pregnancy using washed semen. Conclusion(s) Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized, controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help further reduce the spread of HIV. PMID:26688556

  4. Evolution of HIV-1 coreceptor usage and coreceptor switching during pregnancy.

    Science.gov (United States)

    Ransy, Doris G; Motorina, Alena; Merindol, Natacha; Akouamba, Bertine S; Samson, Johanne; Lie, Yolanda; Napolitano, Laura A; Lapointe, Normand; Boucher, Marc; Soudeyns, Hugo

    2014-03-01

    Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. To document the evolution of coreceptor tropism during pregnancy, a longitudinal study of envelope gene sequences was performed in a group of pregnant women infected with HIV-1 of clade B (n=10) or non-B (n=9). Polymerase chain reaction (PCR) amplification of the V1-V3 region was performed on plasma viral RNA, followed by cloning and sequencing. Using geno2pheno and PSSMX4R5, the presence of X4 variants was predicted in nine of 19 subjects (X4 subjects) independent of HIV-1 clade. Six of nine X4 subjects exhibited CD4(+) T cell counts pregnancy, invariably accompanied by progressive increases in the PSSMX4R5 score, the net charge of V3, and the relative representation of X4 sequences. Evolution toward X4 tropism was also echoed in the primary structure of V2, as an accumulation of substitutions associated with CXCR4 tropism was seen in X4 subjects. Results from these experiments provide the first evidence of the ongoing evolution of coreceptor utilization from CCR5 to CXCR4 during pregnancy in a significant fraction of HIV-infected women. These results inform changes in host-pathogen interactions that lead to a directional shaping of viral populations and viral tropism during pregnancy, and provide insights into the biology of HIV transmission from mother to child.

  5. Dynamics of CD4 Lymphocytes and Viral Load at the Natural History of Perinatal HIV-infection

    Directory of Open Access Journals (Sweden)

    T. A. Daminov

    2015-01-01

    Full Text Available This article presents the analysis of indicators of CD4 lymphocyte count and viral load in the natural history (in the absence of ART in perinatally HIV-infected children. It was revealed that perinatal way of transmission is characterized by a higher rate of immunodeficiency progression. It may be associated with intrauterine infection, as well as an early defeat HIV immature immune system of the child. The concentration of virus in perinatally infected children since the beginning of the observation and in 30 months after infection is more than in parenterally infected children in 5 and 2 times, respectively, which determines a infavourable version of the disease in perinatally infected children.

  6. Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins.

    Science.gov (United States)

    Khan, Sheraz; Iqbal, Mazhar; Tariq, Muhammad; Baig, Shahid M; Abbas, Wasim

    2018-01-01

    HIV-1 latency allows the virus to persist until reactivation, in a transcriptionally silent form in its cellular reservoirs despite the presence of effective cART. Such viral persistence represents a major barrier to HIV eradication since treatment interruption leads to rebound plasma viremia. Polycomb group (PcG) proteins have recently got a considerable attention in regulating HIV-1 post-integration latency as they are involved in the repression of proviral gene expression through the methylation of histones. This epigenetic regulation plays an important role in the establishment and maintenance of HIV-1 latency. In fact, PcG proteins act in complexes and modulate the epigenetic signatures of integrated HIV-1 promoter. Key role played by PcG proteins in the molecular control of HIV-1 latency has led to hypothesize that PcG proteins may represent a valuable target for future HIV-1 therapy in purging HIV-1 reservoirs. In this regard, various small molecules have been synthesized or explored to specifically block the epigenetic activity of PcG. In this review, we will highlight the possible therapeutic approaches to achieve either a functional or sterilizing cure of HIV-1 infection with special focus on histone methylation by PcG proteins together with current and novel pharmacological approaches to reactivate HIV-1 from latency that could ultimately lead towards a better clearance of viral latent reservoirs.

  7. In silico analysis of HIV-1 Env-gp120 reveals structural bases for viral adaptation in growth-restrictive cells

    Directory of Open Access Journals (Sweden)

    Masaru eYokoyama

    2016-02-01

    Full Text Available Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1 envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness.

  8. Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis.

    Science.gov (United States)

    Zafer, Maryam; Horvath, Hacsi; Mmeje, Okeoma; van der Poel, Sheryl; Semprini, Augusto E; Rutherford, George; Brown, Joelle

    2016-03-01

    To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. Systematic review and meta-analysis. Not applicable. Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. Semen washing followed by IUI, IVF, or IVF/ICSI. HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Expansion of Viral Load Testing and the Potential Impact on HIV Drug Resistance.

    Science.gov (United States)

    Raizes, Elliot; Hader, Shannon; Birx, Deborah

    2017-12-01

    The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1

    OpenAIRE

    Pereira,José Moreira; Silva,Cirley Santos da; Porto,Luís Fernando Bruzzi; Póvoa,Luiz Gallotti; Moreira,Aline Santos; Alves,Jorge Roberto

    2002-01-01

    O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika) foi repetidamente positiva na ausência de anticorpo...

  11. HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Antonia Carroll

    2017-03-01

    Full Text Available HIV-associated neurocognitive disorders (HAND remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the “gold standard” of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND. Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.

  12. The histone deacetylase inhibitor vorinostat (SAHA) increases the susceptibility of uninfected CD4+ T cells to HIV by increasing the kinetics and efficiency of postentry viral events.

    Science.gov (United States)

    Lucera, Mark B; Tilton, Carisa A; Mao, Hongxia; Dobrowolski, Curtis; Tabler, Caroline O; Haqqani, Aiman A; Karn, Jonathan; Tilton, John C

    2014-09-01

    Latently infected cells remain a primary barrier to eradication of HIV-1. Over the past decade, a better understanding of the molecular mechanisms by which latency is established and maintained has led to the discovery of a number of compounds that selectively reactivate latent proviruses without inducing polyclonal T cell activation. Recently, the histone deacetylase (HDAC) inhibitor vorinostat has been demonstrated to induce HIV transcription from latently infected cells when administered to patients. While vorinostat will be given in the context of antiretroviral therapy (ART), infection of new cells by induced virus remains a clinical concern. Here, we demonstrate that vorinostat significantly increases the susceptibility of CD4(+) T cells to infection by HIV in a dose- and time-dependent manner that is independent of receptor and coreceptor usage. Vorinostat does not enhance viral fusion with cells but rather enhances the kinetics and efficiency of postentry viral events, including reverse transcription, nuclear import, and integration, and enhances viral production in a spreading-infection assay. Selective inhibition of the cytoplasmic class IIb HDAC6 with tubacin recapitulated the effect of vorinostat. These findings reveal a previously unknown cytoplasmic effect of HDAC inhibitors promoting productive infection of CD4(+) T cells that is distinct from their well-characterized effects on nuclear histone acetylation and long-terminal-repeat (LTR) transcription. Our results indicate that careful monitoring of patients and ART intensification are warranted during vorinostat treatment and indicate that HDAC inhibitors that selectively target nuclear class I HDACs could reactivate latent HIV without increasing the susceptibility of uninfected cells to HIV. HDAC inhibitors, particularly vorinostat, are currently being investigated clinically as part of a "shock-and-kill" strategy to purge latent reservoirs of HIV. We demonstrate here that vorinostat increases the

  13. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

    Science.gov (United States)

    Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

    2009-06-29

    It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with

  14. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

    Directory of Open Access Journals (Sweden)

    Thuy Le

    Full Text Available BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL were obtained from a specimen bank (from 2004-2007. The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36% detected by deep sequencing; the majority of these (95% were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53. The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%. When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016. CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional

  15. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

    Science.gov (United States)

    Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

    2009-01-01

    Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. PMID:19651874

  16. Ultra Structural Characterisation of Tetherin - a Protein Capable of Preventing Viral Release from the Plasma Membrane

    Directory of Open Access Journals (Sweden)

    Ravindra K. Gupta

    2010-04-01

    Full Text Available Tetherin is an antiviral restriction factor made by mammalian cells to protect them from viral infection. It prevents newly formed virus particles from leaving infected cells. Its antiviral mechanism appears to be remarkably uncomplicated. In 2 studies published in PLoS Pathogens electron microscopy is used to support the hypothesis that the tethers that link HIV-1 virions to tetherin expressing cells contain tetherin and are likely to contain tetherin alone. They also show that the HIV-1 encoded tetherin antagonist that is known to cause tetherin degradation, Vpu, serves to reduce the amount of tetherin in the particles thereby allowing their release.

  17. Impact of intimate partner violence on clinic attendance, viral suppression and CD4 cell count of women living with HIV in an urban clinic setting.

    Science.gov (United States)

    Anderson, Jocelyn C; Campbell, Jacquelyn C; Glass, Nancy E; Decker, Michele R; Perrin, Nancy; Farley, Jason

    2018-04-01

    The substance abuse, violence and HIV/AIDS (SAVA) syndemic represents a complex set of social determinants of health that impacts the lives of women. Specifically, there is growing evidence that intimate partner violence (IPV) places women at risk for both HIV acquisition and poorer HIV-related outcomes. This study assessed prevalence of IPV in an HIV clinic setting, as well as the associations between IPV, symptoms of depression and PTSD on three HIV-related outcomes-CD4 count, viral load, and missed clinic visits. In total, 239 adult women attending an HIV-specialty clinic were included. Fifty-one percent (95% CI: 45%-58%) reported past year psychological, physical, or sexual intimate partner abuse. In unadjusted models, IPV was associated with having a CD4 count 33% of past year all type clinic visits (OR: 1.535, 95% CI: 0.920-2.560, p = 0.101) or HIV specialty clinic visits (OR: 1.251, 95% CI: 0.732-2.140). In multivariable regression, controlling for substance use, mental health symptoms and demographic covariates, IPV remained associated with CD4 count suppression. The association between IPV and lower CD4 counts, but not adherence markers such as viral suppression and missed visits, indicates a need to examine potential physiologic impacts of trauma that may alter the immune functioning of women living with HIV. Incorporating trauma-informed approaches into current HIV care settings is one opportunity that begins to address IPV in this patient population.

  18. Associations Between Medicare Part D and Out-of-Pocket Spending, HIV Viral Load, Adherence, and ADAP Use in Dual Eligibles With HIV.

    Science.gov (United States)

    Belenky, Nadya; Pence, Brian W; Cole, Stephen R; Dusetzina, Stacie B; Edmonds, Andrew; Oberlander, Jonathan; Plankey, Michael W; Adedimeji, Adebola; Wilson, Tracey E; Cohen, Jennifer; Cohen, Mardge H; Milam, Joel E; Golub, Elizabeth T; Adimora, Adaora A

    2018-01-01

    The implementation of Medicare part D on January 1, 2006 required all adults who were dually enrolled in Medicaid and Medicare (dual eligibles) to transition prescription drug coverage from Medicaid to Medicare part D. Changes in payment systems and utilization management along with the loss of Medicaid protections had the potential to disrupt medication access, with uncertain consequences for dual eligibles with human immunodeficiency virus (HIV) who rely on consistent prescription coverage to suppress their HIV viral load (VL). To estimate the effect of Medicare part D on self-reported out-of-pocket prescription drug spending, AIDS Drug Assistance Program (ADAP) use, antiretroviral adherence, and HIV VL suppression among dual eligibles with HIV. Using 2003-2008 data from the Women's Interagency HIV Study, we created a propensity score-matched cohort and used a difference-in-differences approach to compare dual eligibles' outcomes pre-Medicare and post-Medicare part D to those enrolled in Medicaid alone. Transition to Medicare part D was associated with a sharp increase in the proportion of dual eligibles with self-reported out-of-pocket prescription drug costs, followed by an increase in ADAP use. Despite the increase in out-of-pocket costs, both adherence and HIV VL suppression remained stable. Medicare part D was associated with increased out-of-pocket spending, although the increased spending did not seem to compromise antiretroviral therapy adherence or HIV VL suppression. It is possible that increased ADAP use mitigated the increase in out-of-pocket spending, suggesting successful coordination between Medicare part D and ADAP as well as the vital role of ADAP during insurance transitions.

  19. Subtype-independent near full-length HIV-1 genome sequencing and assembly to be used in large molecular epidemiological studies and clinical management.

    Science.gov (United States)

    Grossmann, Sebastian; Nowak, Piotr; Neogi, Ujjwal

    2015-01-01

    HIV-1 near full-length genome (HIV-NFLG) sequencing from plasma is an attractive multidimensional tool to apply in large-scale population-based molecular epidemiological studies. It also enables genotypic resistance testing (GRT) for all drug target sites allowing effective intervention strategies for control and prevention in high-risk population groups. Thus, the main objective of this study was to develop a simplified subtype-independent, cost- and labour-efficient HIV-NFLG protocol that can be used in clinical management as well as in molecular epidemiological studies. Plasma samples (n=30) were obtained from HIV-1B (n=10), HIV-1C (n=10), CRF01_AE (n=5) and CRF01_AG (n=5) infected individuals with minimum viral load >1120 copies/ml. The amplification was performed with two large amplicons of 5.5 kb and 3.7 kb, sequenced with 17 primers to obtain HIV-NFLG. GRT was validated against ViroSeq™ HIV-1 Genotyping System. After excluding four plasma samples with low-quality RNA, a total of 26 samples were attempted. Among them, NFLG was obtained from 24 (92%) samples with the lowest viral load being 3000 copies/ml. High (>99%) concordance was observed between HIV-NFLG and ViroSeq™ when determining the drug resistance mutations (DRMs). The N384I connection mutation was additionally detected by NFLG in two samples. Our high efficiency subtype-independent HIV-NFLG is a simple and promising approach to be used in large-scale molecular epidemiological studies. It will facilitate the understanding of the HIV-1 pandemic population dynamics and outline effective intervention strategies. Furthermore, it can potentially be applicable in clinical management of drug resistance by evaluating DRMs against all available antiretrovirals in a single assay.

  20. Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

    Science.gov (United States)

    Lee, SoYong; Chung, Yoon-Seok; Yoon, Cheol-Hee; Shin, YoungHyun; Kim, SeungHyun; Choi, Byeong-Sun; Kim, Sung Soon

    2015-05-01

    Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system. Early HIV-1 infection was classified according to the Fiebig stage (FS) based on the characteristics of the patients infected with HIV-1. Concentrations of interleukin-12 (IL-12), interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1α (MIP-1α) and regulated upon activation, normal T cells expressed and secreted (RANTES) were increased significantly during the early stage of HIV-1 infection (FS II-IV) compared with the HIV-1-negative group. Of these cytokines, an elevated level of IP-10 was the only factor to be correlated positively with a higher viral load during the early stages of HIV-1 infection (FS II-IV) in Koreans (R = 0.52, P IP-10 may be an indicator for HIV-1 viremia and associated closely with viral replication in patients with early HIV-1 infection. © 2015 Wiley Periodicals, Inc.

  1. Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.

    Directory of Open Access Journals (Sweden)

    Asres Berhan

    Full Text Available The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative, Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61-4.52 than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir. Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15-4.11. Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent

  2. High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

    Directory of Open Access Journals (Sweden)

    Cissy Kityo

    Full Text Available In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM versus routine laboratory (CD4/haematology/biochemistry and clinical monitoring (LCM in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317 participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717, abacavir (n = 300, or nevirapine (n = 300. Of 1896 (81.8% participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation, 1507 (79.5% were on first-line and 389 (20.5% on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3. Among 1207 (80.1% first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%, 400-999 copies/ml in 37 (3.1%, 1,000-9,999 copies/ml in 110 (9.1%, and ≥10,000 copies/ml in 97 (8.0%. The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5% in CDM (76.3% than in LCM (83.4%. Among 252 (64.8% second-line participants with viral load measured (median 2.3 years after switch, HIV RNA was <400 copies/ml in 226 (89.7%, with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.ISRCTN13968779.

  3. [HIV and pregnancy: 2013 guidelines from the French expert working group].

    Science.gov (United States)

    Mandelbrot, L; Berrébi, A; Matheron, S; Blanche, S; Tubiana, R; Rouzioux, C; Faucher, P; Partisani, M; Boyer, V; Taeron, C; Faye, A; Bujan, L; Dabis, F; Warszawski, J; Morlat, P

    2014-09-01

    With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is>400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is>1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. HIV: Social and Environmental Factors

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses how social and environmental factors may put African Americans at greater risk for HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  5. Innate immune reconstitution with suppression of HIV-1.

    Science.gov (United States)

    Scully, Eileen P; Lockhart, Ainsley; Garcia-Beltran, Wilfredo; Palmer, Christine D; Musante, Chelsey; Rosenberg, Eric; Allen, Todd M; Chang, J Judy; Bosch, Ronald J; Altfeld, Marcus

    2016-03-17

    Progressive HIV-1 infection leads to both profound immune suppression and pathologic inflammation in the majority of infected individuals. While adaptive immune dysfunction, as evidenced by CD4 + T cell depletion and exhaustion, has been extensively studied, less is known about the functional capacity of innate immune cell populations in the context of HIV-1 infection. Given the broad susceptibility to opportunistic infections and the dysregulated inflammation observed in progressive disease, we hypothesized that there would be significant changes in the innate cellular responses. Using a cohort of patients with multiple samplings before and after antiretroviral therapy (ART) initiation, we demonstrated increased responses to innate immune stimuli following viral suppression, as measured by the production of inflammatory cytokines. Plasma viral load itself had the strongest association with this change in innate functional capacity. We further identified epigenetic modifications in the TNFA promoter locus in monocytes that are associated with viremia, suggesting a molecular mechanism for the observed changes in innate immune function following initiation of ART. These data indicate that suppression of HIV-1 viremia is associated with changes in innate cellular function that may in part determine the restoration of protective immune responses.

  6. Differentiation of HIV-associated lymphoma from HIV-associated reactive adenopathy using quantitative FDG PET and symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Mhlanga, Joyce C.; Durand, Daniel; Leal, Jeffrey P. [Johns Hopkins University School of Medicine, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Tsai, Hua-Ling; Wang, Hao [Johns Hopkins University School of Medicine, Department of Oncology Biostatistics Division, Baltimore, MD (United States); Durand, Christine M.; Moore, Richard [Johns Hopkins University School of Medicine, Maryland Infectious Diseases Department, Baltimore, MD (United States); Wahl, Richard L. [Johns Hopkins University School of Medicine, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD (United States)

    2014-04-15

    To determine the diagnostic accuracy of a semiautomated {sup 18}F-FDG PET/CT measurement of total lesion glycolysis (TLG), maximum and peak standardized uptake value at lean body mass (SUL-Max and SUL-Peak), qualitative estimates of left/right nodal symmetry and FDG uptake for differentiating lymphoma from reactive adenopathy in HIV-infected patients. We retrospectively analyzed 41 whole-body {sup 18}F-FDG PET/CT studies performed in HIV-infected patients for clinical reasons. The study received institutional review board approval. Of the 41 patients, 19 had biopsy-proven untreated lymphoma, and 22 with reactive adenopathy without malignancy on follow-up were used as controls. Nodal and extranodal visual qualitative metabolic scores, SUL-Max, SUL-Peak, CT nodal size, and PERCIST 1.0 threshold-based TLG and metabolic tumor volume (MTV) were determined. The qualitative intensity of nodal involvement and symmetry of uptake were compared using receiver operator curve (ROC) analysis. HIV plasma viral RNA measurements were also obtained. All of the quantitative PET metrics performed well in differentiating lymphoma from reactive adenopathy and performed better than qualitative visual intensity scores. The areas under the ROC curves (AUC) were significantly higher for TLG = 0.96, single SUL-Peak = 0.96, single SUL-Max = 0.97, and MTV = 0.96, compared to 0.67 for CT nodal size (p < 0.001). These PET metrics performed best in separating the two populations in aviremic patients, with AUCs of 1 (AUC 0.91 for CT nodal size). TLG, MTV, SUL-Peak and SUL-Max were more reliable markers among viremic individuals, with AUCs between 0.84 and 0.93, compared to other metrics. PET metrics were significantly correlated with plasma viral load in HIV-reactive adenopathy controls. Asymmetrical FDG uptake had an accuracy of 90.4 % for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Quantitative PET metabolic metrics as well as the qualitative assessment of

  7. High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems

    Directory of Open Access Journals (Sweden)

    Yin Li

    2012-12-01

    Full Text Available Abstract Background Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. While extensively applied to microbiome studies, population genetics studies of viruses are limited. To define the scope of HIV-1 population biodiversity within infected individuals, a suite of phylogenetic and population genetic algorithms was applied to HIV-1 envelope hypervariable domain 3 (Env V3 within peripheral blood mononuclear cells from a group of perinatally HIV-1 subtype B infected, therapy-naïve children. Results Biodiversity of HIV-1 Env V3 quasispecies ranged from about 70 to 270 unique sequence clusters across individuals. Viral population structure was organized into a limited number of clusters that included the dominant variants combined with multiple clusters of low frequency variants. Next generation viral quasispecies evolved from low frequency variants at earlier time points through multiple non-synonymous changes in lineages within the evolutionary landscape. Minor V3 variants detected as long as four years after infection co-localized in phylogenetic reconstructions with early transmitting viruses or with subsequent plasma virus circulating two years later. Conclusions Deep sequencing defines HIV-1 population complexity and structure, reveals the ebb and flow of dominant and rare viral variants in the host ecosystem, and identifies an evolutionary record of low-frequency cell-associated viral V3 variants that persist for years. Bioinformatics pipeline developed for HIV-1 can be applied for biodiversity studies of virome populations in human, animal, or plant ecosystems.

  8. Correlation between lamivudine plasma concentrations and patient self-reported adherence to antiretroviral treatment in experienced HIV patients

    Directory of Open Access Journals (Sweden)

    Minzi OM

    2011-11-01

    Full Text Available OM Minzi1, V Mugoyela2, LL Gustafsson31Unit of Pharmacology and Therapeutics, 2Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, SwedenBackground: Adherence to antiretroviral treatment (ART is important to achieve treatment success in human immunodeficiency virus (HIV-infected patients. Most HIV clinics apply the patient self-report (PSR method. However, the reliability of this method in experienced HIV patients remains questionable.Purpose: To validate the PSR method for measuring adherence to ART using lamivudine (3TC plasma concentrations in experienced HIV patients.Methods: The study was conducted in Dar Es Salaam and involved 220 patients who were receiving ART services at HIV clinics for more than 12 months. Self-reported adherence information to ART was obtained on the day of HIV clinic visit. The patients were asked to mention the number of doses missed within the past 7 days. In addition, blood samples (2 mL were collected from each patient on the same day. The blood samples were determined for 3TC plasma concentrations. The target 3TC plasma concentration as indicator concentration for adherent patients was determined in 20 patients who took their evening dose of antiretrovirals under supervision. The blood from these patients was drawn 3 hours after drug administration.Results: Complete drug levels of 3TC and self-reported adherence data was obtained in 200 treatment-experienced HIV patients. Lamivudine plasma concentrations obtained in these patients ranged between 0.02–17.36 µg/mL. The mean time from dose administration to blood drawing was 3.1 ± 1.2 hours with coefficient of variation >39%. The mean 3TC plasma concentration obtained in 20 patients who took their antiretroviral dose under supervision was

  9. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  10. Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study

    DEFF Research Database (Denmark)

    Peters, Lars; Neuhaus, Jacqueline; Duprez, Daniel

    2014-01-01

    BACKGROUND: Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy (ART). OBJECTIVES: To investigate the influence of fibrosis and ART interruption...... on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study. STUDY DESIGN: All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic...

  11. Community-driven demand creation for the use of routine viral load testing: a model to scale up routine viral load testing.