Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

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Korber, Bette Tina Marie [Los Alamos National Laboratory

2008-01-01

The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

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.

Clinical and Epidemiological Characteristics of HIV Infection/AIDS in Hospitalized Patients.

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Ahmetagic, Sead; Porobić-Jahic, Humera; Piljic, Dilista; Custovic, Amer; Sabitovic, Damir; Zepic, Denis

2015-02-01

More than three decades after recognition of acquired immunodeficiency syndrome (AIDS) in the United States, the pandemic of human immunodeficiency virus (HIV) infection has dramatically changed the global burden of disease. The main goal of this research is retrospective analysis of epidemiological and clinical characteristics of 28 HIV infected patients, who were diagnosed and treated at the Clinic for Infectious Diseases in University Clinical Center Tuzla in the period from 1996 until the end of 2013. Retrospective analysis was performed using the medical records of 28 HIV-infected persons. Two rapid tests were used for HIV testing: OraQuick Advance test, Vikia HIV1/2, Elisa combo test, HIV RNA test. AIDS disease was determined by using the criteria from WHO. Among a total of 28 HIV-infected persons, 23 (82.14%) were males and 5 (17.86%) were females, with the male: female ratio of 4,6:1. In terms of the transmission route, a large proportion of cases were infected through heterosexual contact 19 (67.86%). At the time of the first visit, 16 (57.15%) patients showed asymptomatic HIV infection, 4 (14.28%) HIV infection with symptoms other than the AIDS defining diseases, and 8 (28.57) had AIDS. At the time of first hospital visit, the CD4 + cells count ranged from 40 to 1795/µl (conducted in 19 patients), and mean value of CD4 + cells was 365,31/µl, and mean HIV RNA titer was 287 118 copies/ml³. Of 28 HIV-infected persons 39 cases of opportunistic diseases developed in 12 patients (42.9%). In terms of the frequency of opportunistic diseases, tuberculosis (12 cases, 42.9%). Among a total of 28 HIV-infected patients, 6 (21.4%) of them died. This study characterizes the epidemiological and clinical patterns of HIV-infected patients in Tuzla region of Bosnia and Herzegovina to accurately understand HIV infection/AIDS in our region, in the hope to contribute in the establishment of effective HIV guidelines in the Tuzla region of B&H in the future.

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.

Teste rápido para detecção da infecção pelo HIV-1 em gestantes Rapid test to detect HIV-1 infection among pregnant women

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Geraldo Duarte

2001-03-01

Full Text Available Objetivos: avaliar os resultados do teste de diagnóstico rápido da infecção pelo HIV-1 disponibilizado pelo Ministério da Saúde, para identificação de gestantes contaminadas por este vírus. Métodos: avaliação prospectiva de 443 gestantes sem teste sorológico para HIV no pré-natal, atendidas no Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto-Universidade de São Paulo (HCFMRP-USP, entre fevereiro e junho de 2000. As amostras destas pacientes foram submetidas ao teste rápido imunocromatográfico, sendo comparadas com ELISA e confirmadas pela aglutinação. Resultados: dentre as 443 gestantes submetidas ao teste rápido (20,1% dos partos no período, 16 apresentaram resultados positivos (3,6%. Nenhuma amostra negativa pelo teste rápido foi positiva pelo ELISA. Entretanto, das 16 amostras positivas pelo teste rápido, duas foram negativas pelos testes confirmatórios. Logo, a sensibilidade do teste rápido foi de 100,0%, especificidade 99,5%, valor preditivo positivo 87,5% e valor preditivo negativo 100,0%. Conclusões: os resultados obtidos na avaliação do teste para o diagnóstico rápido da infecção pelo HIV-1 em gestantes revelaram sensibilidade, especificidade e valores preditivos que o credenciam como recurso extremamente importante na indicação de medidas que reduzem a transmissão perinatal desse vírus.Purpose: to evaluate the results of a rapid diagnostic test for HIV-1 infection made available by the Health Ministry for the identification of pregnant women contaminated by this virus. Methods: we evaluated prospectively 443 pregnant women with no prenatal serologic anti-HIV test seen at the Department of Gynecology and Obstetrics of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, from February to June, 2000. Samples from these patients were submitted to the rapid immunochromatographic test, which was compared with ELISA and submitted to a confirmatory

Potential for false positive HIV test results with the serial rapid HIV testing algorithm.

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Baveewo, Steven; Kamya, Moses R; Mayanja-Kizza, Harriet; Fatch, Robin; Bangsberg, David R; Coates, Thomas; Hahn, Judith A; Wanyenze, Rhoda K

2012-03-19

Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

Evaluation of Blood-Based Antibody Rapid Testing for HIV Early Therapy: A Meta-Analysis of the Evidence

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Xiaojie Huang

2018-06-01

Full Text Available BackgroundWestern blot (WB assay is considered the gold standard test for HIV infection confirmation. However, it requires technical expertise and is quite time-consuming. WHO recommends blood-based rapid diagnosis to achieve same-day test and treatment. However, this rapid testing strategy has not been promoted worldwide due to inadequate research evaluating the effectiveness of rapid tests (RTs as an alternative confirmatory HIV test for WB. This study aims to compare the diagnostic performance of rapid HIV tests compared with WB.MethodsPubMed and Web of Science were searched for publications on rapid HIV tests using blood specimen. A meta-analysis was performed to quantitatively evaluate the diagnostic performance of rapid HIV tests compared with the WB assay in terms of pooled sensitivity, specificity, area under summary receiver operating characteristic (SROC curve, and diagnostic odds ratio (DOR.ResultsTwenty articles involving 27,343 fresh specimens for rapid HIV tests were included in the meta-analysis. Regarding Capillus HIV-1/HIV-2, the pooled sensitivity, specificity, area under SROC curve, and DOR derived from six studies were 0.999 (95% CI, 0.956–1.000, 0.999 (95% CI, 0.991–1.00, 1.00 (95% CI, 0.99–1.00, and 1.0 × 106 (95% CI, 2.6 × 104–3.9 × 107 compared with the WB assay, respectively. With respect to Determine HIV-1/2, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 1.00 (95% CI, 0.789–1.000, 0.992 (95% CI, 0.985–0.996, 1.00 (95% CI, 0.99–1.00, and 1.8 × 106 (95% CI 406.049–7.8 × 109 compared with the WB assay, respectively. Regarding two-step serial RTs, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 0.998 (95% CI, 0.991–1.000, 0.998 (95% CI, 0.994–0.999, and 1.00 (95% CI 0.99–1.00 compared with the WB assay, respectively.ConclusionOur meta-analysis results may provide evidenced-based support

Potential for false positive HIV test results with the serial rapid HIV testing algorithm

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Baveewo Steven

2012-03-01

Full Text Available Abstract Background Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Results Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold. However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2% were HIV negative. Conclusion Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

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

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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.

Factors associated with willingness to accept oral fluid HIV rapid testing among most-at-risk populations in China.

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Huanmiao Xun

Full Text Available The availability of oral fluid HIV rapid testing provides an approach that may have the potential to expand HIV testing in China, especially among most-a-risk populations. There are few investigations about the acceptability of oral fluid HIV testing among most-at-risk populations in China.A cross-sectional study with men who have sex with men (MSM, female sex workers (FSW and voluntary counseling and testing (VCT clients was conducted in three cities of Shandong province, China from 2011 to 2012. Data were collected by face-to-face questionnaire.About 71% of participants were willing to accept the oral fluid HIV rapid testing, and home HIV testing was independently associated with acceptability of the new testing method among MSM, FSW and VCT clients (AOR of 4.46, 3.19 and 5.74, respectively. Independent predictors of oral fluid HIV rapid testing acceptability among MSM were having ever taken an oral fluid HIV rapid test (AOR= 15.25, having ever taken an HIV test (AOR= 2.07, and education level (AOR= 1.74. Engagement in HIV-related risk behaviors (AOR= 1.68 was an independent predictor of acceptability for FSW. Having taken an HIV test (AOR= 2.85 was an independent predictor of acceptability for VCT clients. The primary concern about the oral fluid HIV testing was accuracy. The median price they would pay for the testing ranged from 4.8 to 8.1 U.S. dollars.High acceptability of oral fluid HIV rapid testing was shown among most-at-risk populations. Findings provide support for oral rapid HIV testing as another HIV prevention tool, and provide a backdrop for the implementation of HIV home testing in the near future. Appropriate pricing and increased public education through awareness campaigns that address concerns about the accuracy and safety of the oral fluid HIV rapid testing may help increase acceptability and use among most-at-risk populations in China.

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

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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.

Non-reactive HIV-1 Rapid Tests after Sustained Viral Suppression Following Antiretroviral Therapy Initiation During Primary Infection.

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Stefic, Karl; Novelli, Sophie; Mahjoub, Nadia; Seng, Remonie; Molina, Jean-Michel; Cheneau, Christine; Barin, Francis; Chaix, Marie-Laure; Meyer, Laurence; Delaugerre, Constance

2018-03-02

We assessed the impact of early antiretroviral treatment (ART) on HIV antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in respectively 30% and 7-9% of cases. These data reinforce the message that patients should never be retested after entering HIV care.

Cutting edge: Rapid recovery of NKT cells upon institution of highly active antiretroviral therapy for HIV-1 infection

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van der Vliet, Hans J. J.; van Vonderen, Marit G. A.; Molling, Johan W.; Bontkes, Hetty J.; Reijm, Martine; Reiss, Peter; van Agtmael, Michiel A.; Danner, Sven A.; van den Eertwegh, Alfons J. M.; von Blomberg, B. Mary E.; Scheper, Rik J.

2006-01-01

CD1d-restricted NKT cells play important regulatory roles in various immune responses and are rapidly and selectively depleted upon infection with HIV-1. The cause of this selective depletion is incompletely understood, although it is in part due to the high susceptibility of CD4+ NKT cells to

Performance of 3 Rapid Tests for Discrimination Between HIV-1 and HIV-2 in Guinea-Bissau, West Africa

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Hønge, Bo Langhoff; Bjarnason Obinah, Magnús Pétur; Jespersen, Sanne

2014-01-01

As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated ...... (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation....

Operational feasibility of using whole blood in the rapid HIV testing algorithm of a resource-limited settings like Bangladesh.

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Munshi, Saif U; Oyewale, Tajudeen O; Begum, Shahnaz; Uddin, Ziya; Tabassum, Shahina

2016-03-01

Serum-based rapid HIV testing algorithm in Bangladesh constitutes operational challenge to scaleup HIV testing and counselling (HTC) in the country. This study explored the operational feasibility of using whole blood as alternative to serum for rapid HIV testing in Bangladesh. Whole blood specimens were collected from two study groups. The groups included HIV-positive patients (n = 200) and HIV-negative individuals (n = 200) presenting at the reference laboratory in Dhaka, Bangladesh. The specimens were subjected to rapid HIV tests using the national algorithm with A1 = Alere Determine (United States), A2 = Uni-Gold (Ireland), and A3 = First Response (India). The sensitivity and specificity of the test results, and the operational cost were compared with current serum-based testing. The sensitivities [95% of confidence interval (CI)] for A1, A2, and A3 tests using whole blood were 100% (CI: 99.1-100%), 100% (CI: 99.1-100%), and 97% (CI: 96.4-98.2%), respectively, and specificities of all test kits were 100% (CI: 99.1-100%). Significant (P < 0.05) reduction in the cost of establishing HTC centre and consumables by 94 and 61%, respectively, were observed. The cost of administration and external quality assurance reduced by 39 and 43%, respectively. Overall, there was a 36% cost reduction in total operational cost of rapid HIV testing with blood when compared with serum. Considering the similar sensitivity and specificity of the two specimens, and significant cost reduction, rapid HIV testing with whole blood is feasible. A review of the national HIV rapid testing algorithm with whole blood will contribute toward improving HTC coverage in Bangladesh.

Lack of HIV infection among truck drivers in Iran using rapid HIV test

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Hossain Jabbari

2010-01-01

Full Text Available Background: The aim of this study was to evaluate the prevalence of HIV infection in Iranian long distance truck drivers using rapid HIV test. Methods: The study included 400 consecutive participants in Bazargan city, north-west of Iran in the late 2008 and the early 2009. Results: No HIV infection was observed among these long distance truck drivers. Conclusions: Although results of this study is plausible compared to other similar studies, repeated surveys are necessary to know the trend of HIV infection in truckers in Iran.

Evaluation of Performance of Two Rapid Tests for Detection of HIV-1 and -2 in High- and Low-Prevalence Populations in Nigeria.

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Manak, Mark M; Njoku, Ogbonnaya S; Shutt, Ashley; Malia, Jennifer; Jagodzinski, Linda L; Milazzo, Mark; Suleiman, Aminu; Ogundeji, Amos A; Nelson, Robert; Ayemoba, Ojor R; O'Connell, Robert J; Singer, Darrell E; Michael, Nelson L; Peel, Sheila A

2015-11-01

The availability of reliable human immunodeficiency virus types 1 and 2 (HIV-1/2) rapid tests in resource-limited settings represents an important advancement in the accurate diagnosis of HIV infection and presents opportunities for implementation of effective prevention and treatment interventions among vulnerable populations. A study of the potential target populations for future HIV vaccine studies examined the prevalence of HIV infections at six selected sites in Nigeria and evaluated the use of two rapid diagnostic tests (RDTs) for HIV. The populations included market workers at sites adjacent to military installations and workers at highway settlements (truck stops) who may have a heightened risk of HIV exposure. Samples from 3,187 individuals who provided informed consent were tested in parallel using the Determine (DT) and Stat-Pak (SP) RDTs; discordant results were subjected to the Uni-Gold (UG) RDT as a tiebreaker. The results were compared to those of a third-generation enzyme immunoassay screen with confirmation of repeat reactive samples by HIV-1 Western blotting. One participant was HIV-2 infected, yielding positive results on both RDTs. Using the laboratory algorithm as a gold standard, we calculated sensitivities of 98.5% (confidence interval [CI], 97.1 to 99.8%) for DT and 98.1% (CI, 96.7 to 99.6%) for SP and specificities of 98.7% (CI, 98.3 -99.1%) for DT and 99.8% (CI, 99.6 to 100%) for SP. Similar results were obtained when the sites were stratified into those of higher HIV prevalence (9.4% to 22.8%) versus those of lower prevalence (3.2% to 7.3%). A parallel two-test algorithm requiring both DT and SP to be positive resulted in the highest sensitivity (98.1%; CI, 96.7 to 99.6%) and specificity (99.97%; CI, 99.9 to 100%) relative to those for the reference laboratory algorithm. Copyright © 2015, Manak et al.

Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

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Fogel, Jessica M; Piwowar-Manning, Estelle; Debevec, Barbara; Walsky, Tamara; Schlusser, Katherine; Laeyendecker, Oliver; Wilson, Ethan A; McCauley, Marybeth; Gamble, Theresa; Tegha, Gerald; Soko, Dean; Kumwenda, Johnstone; Hosseinipour, Mina C; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2017-08-01

Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

Structural defects and variations in the HIV-1 nef gene from rapid, slow and non-progressor children.

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Casartelli, Nicoletta; Di Matteo, Gigliola; Argentini, Claudio; Cancrini, Caterina; Bernardi, Stefania; Castelli, Guido; Scarlatti, Gabriella; Plebani, Anna; Rossi, Paolo; Doria, Margherita

2003-06-13

Evaluation of sequence evolution as well as structural defects and mutations of the human immunodeficiency virus-type 1 (HIV-1) nef gene in relation to disease progression in infected children. We examined a large number of nef alleles sequentially derived from perinatally HIV-1-infected children with different rates of disease progression: six non-progressors (NPs), four rapid progressors (RPs), and three slow progressors (SPs). Nef alleles (182 total) were isolated from patients' peripheral blood mononuclear cells (PBMCs), sequenced and analysed for their evolutionary pattern, frequency of mutations and occurrence of amino acid variations associated with different stages of disease. The evolution rate of the nef gene apparently correlated with CD4+ decline in all progression groups. Evidence for rapid viral turnover and positive selection for changes were found only in two SPs and two RPs respectively. In NPs, a higher proportion of disrupted sequences and mutations at various functional motifs were observed. Furthermore, NP-derived Nef proteins were often changed at residues localized in the folded core domain at cytotoxic T lymphocytes (CTL) epitopes (E(105), K(106), E(110), Y(132), K(164), and R(200)), while other residues outside the core domain are more often changed in RPs (A(43)) and SPs (N(173) and Y(214)). Our results suggest a link between nef gene functions and the progression rate in HIV-1-infected children. Moreover, non-progressor-associated variations in the core domain of Nef, together with the genetic analysis, suggest that nef gene evolution is shaped by an effective immune system in these patients.

Usage and acceptability of HIV self-testing in men who have sex with men in Hong Kong.

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Wong, Horas Tze Hoo; Tam, Hoi Yan; Chan, Denise Pui Chung; Lee, Shui Shan

2015-03-01

Whilst studies on over-the-counter HIV tests continue to accumulate after FDA's approval of OraQuick Advance in 2012, few have focused on men who have sex with men (MSM) in Asian cities. An internet survey was conducted on 1,122 MSM in Hong Kong, revealing a low usage (6.1 %) and acceptability rate (43.8 %) on self-testing despite its availability in the market. Hierarchical logistic regression models showed that having received relevant information and users' attitudes on self-testing were the determinants of usage and acceptability. These factors had greater effects than sexual behaviors and social-networking on MSM's decision on self-testing. Majority of ever self-testers only repeated the self-test after a non-negative result, and overall only 26.6 % went for a formal test subsequent to the self-test. Concerns regarding the tests' accuracy were expressed by respondents. In conclusion, appropriate and accessible information and evidence-based guidance are needed to incorporate self-testing into HIV prevention strategies targeting MSM.

Detection of Acute and Early HIV-1 Infections in an HIV Hyper-Endemic Area with Limited Resources.

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Simnikiwe H Mayaphi

Full Text Available Two thirds of the world's new HIV infections are in sub-Saharan Africa. Acute HIV infection (AHI is the time of virus acquisition until the appearance of HIV antibodies. Early HIV infection, which includes AHI, is the interval between virus acquisition and establishment of viral load set-point. This study aimed to detect acute and early HIV infections in a hyper-endemic setting.This was a cross-sectional diagnostic study that enrolled individuals who had negative rapid HIV results in five clinics in South Africa. Pooled nucleic acid amplification testing (NAAT was performed, followed by individual sample testing in positive pools. NAAT-positive participants were recalled to the clinics for confirmatory testing and appropriate management. HIV antibody, p24 antigen, Western Blot and avidity tests were performed for characterization of NAAT-positive samples.The study enrolled 6910 individuals with negative rapid HIV results. Median age was 27 years (interquartile range {IQR}: 23-31. NAAT was positive in 55 samples, resulting in 0.8% newly diagnosed HIV-infected individuals (95% confidence interval {CI}: 0.6-1.0. The negative predictive value for rapid HIV testing was 99.2% (95% CI: 99.0-99.4. Characterization of NAAT-positive samples revealed that 0.04% (95% CI: 0.000-0.001 had AHI, 0.3% (95% CI: 0.1-0.4 had early HIV infection, and 0.5% (95% CI: 0.5-0.7 had chronic HIV infection. Forty-seven (86% of NAAT-positive participants returned for follow-up at a median of 4 weeks (IQR: 2-8. Follow-up rapid tests were positive in 96% of these participants.NAAT demonstrated that a substantial number of HIV-infected individuals are misdiagnosed at South African points-of-care. Follow-up rapid tests done within a 4 week interval detected early and chronic HIV infections initially missed by rapid HIV testing. This may be a practical and affordable strategy for earlier detection of these infections in resource-constrained settings. Newer molecular tests that can

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

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Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

2017-01-01

New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

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Xinli Lu

Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

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

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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.

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.

Acceptability of rapid HIV diagnosis technology among primary healthcare practitioners in Spain.

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Agustí, C; Fernàndez-López, L; Mascort, J; Carrillo, R; Aguado, C; Montoliu, A; Puigdengolas, X; De La Poza, M; Rifà, B; Casabona, J

2013-01-01

This study investigated the acceptability of rapid HIV testing among general practitioners (GP) and aimed to identify perceived barriers and needs in order to implement rapid testing in primary care settings. An anonymous questionnaire was distributed online to all members of the two largest Spanish scientific medical societies for family and community medicine. The study took place between 15 June 2012 and 31 October 2010. Completed questionnaires were returned by 1308 participants. The majority (90.8%) of respondents were GP. Among all respondents, 70.4% were aware of the existence of rapid tests for the diagnosis of HIV but they did not know how to use them. Nearly 80% of participants would be willing to offer rapid HIV testing in their practices and 74.7% would be confident of the result obtained by these tests. The barriers most commonly identified by respondents were a lack of time and a need for training, both in the use of rapid tests (44.3% and 56.4%, respectively) and required pre- and post-test counselling (59.2% and 34.5%, respectively). This study reveals a high level of acceptance and willingness on the part of GPs to offer rapid HIV testing in their practices. Nevertheless, the implementation of rapid HIV testing in primary care will not be possible without moving from comprehensive pre-test counselling towards brief pre-test information and improving training in the use of rapid tests.

Comparative effectiveness of single and dual rapid diagnostic tests for syphilis and HIV in antenatal care services in Colombia.

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Gaitán-Duarte, Hernando Guillermo; Newman, Lori; Laverty, Maura; Habib, Ndema Abu; González-Gordon, Lina María; Ángel-Müller, Edith; Abella, Catleya; Barros, Esther Cristina; Rincón, Carlos; Caicedo, Sidia; Gómez, Bertha; Pérez, Freddy

2016-12-01

To assess the effectiveness of a dual rapid test compared to a single rapid test for syphilis and HIV screening. A cluster-randomized open-label clinical trial was performed in 12 public antenatal care (ANC) centers in the cities of Bogotá and Cali, Colombia. Pregnant women who were over 14 years of age at their first antenatal visit and who had not been previously tested for HIV and syphilis during the current pregnancy were included. Pregnant women were randomized to single HIV and single syphilis rapid diagnostic tests (Arm A) or to dual HIV and syphilis rapid diagnostic tests (Arm B). The four main outcomes measured were: (1) acceptability of the test, (2) uptake in testing, (3) treatment on the same day (that is, timely treatment), and (4) treatment at any time for positive rapid test cases. Bivariate and multivariate analyses were calculated to adjust for the clustering effect and the period. A total of 1 048 patients were analyzed in Arm A, and 1 166 in Arm B. Acceptability of the rapid tests was 99.8% in Arm A and 99.6% in Arm B. The prevalence of positive rapid tests was 2.21% for syphilis and 0.36% for HIV. Timely treatment was provided to 20 of 29 patients (69%) in Arm A and 16 of 20 patients (80%) in Arm B (relative risk (RR), 1.10; 95% confidence interval (CI): (1.00 -1.20). Treatment at any time was given to 24 of 29 patients (83%) in Arm A and to 20 of 20 (100%) in Arm B (RR, 1.11; 95% CI: 1.01-1.22). There were no differences in patient acceptability, testing and timely treatment between dual rapid tests and single rapid tests for HIV and syphilis screening in the ANC centers. Same-day treatment depends also on the interpretation of and confidence in the results by the health providers.

Comparative effectiveness of single and dual rapid diagnostic tests for syphilis and HIV in antenatal care services in Colombia

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Hernando Guillermo Gaitán-Duarte

Full Text Available ABSTRACT Objective To assess the effectiveness of a dual rapid test compared to a single rapid test for syphilis and HIV screening. Methods A cluster-randomized open-label clinical trial was performed in 12 public antenatal care (ANC centers in the cities of Bogotá and Cali, Colombia. Pregnant women who were over 14 years of age at their first antenatal visit and who had not been previously tested for HIV and syphilis during the current pregnancy were included. Pregnant women were randomized to single HIV and single syphilis rapid diagnostic tests (Arm A or to dual HIV and syphilis rapid diagnostic tests (Arm B. The four main outcomes measured were: (1 acceptability of the test, (2 uptake in testing, (3 treatment on the same day (that is, timely treatment, and (4 treatment at any time for positive rapid test cases. Bivariate and multivariate analyses were calculated to adjust for the clustering effect and the period. Results A total of 1 048 patients were analyzed in Arm A, and 1 166 in Arm B. Acceptability of the rapid tests was 99.8% in Arm A and 99.6% in Arm B. The prevalence of positive rapid tests was 2.21% for syphilis and 0.36% for HIV. Timely treatment was provided to 20 of 29 patients (69% in Arm A and 16 of 20 patients (80% in Arm B (relative risk (RR, 1.10; 95% confidence interval (CI: (1.00 −1.20. Treatment at any time was given to 24 of 29 patients (83% in Arm A and to 20 of 20 (100% in Arm B (RR, 1.11; 95% CI: 1.01−1.22. Conclusions There were no differences in patient acceptability, testing and timely treatment between dual rapid tests and single rapid tests for HIV and syphilis screening in the ANC centers. Same-day treatment depends also on the interpretation of and confidence in the results by the health providers.

Evaluation of nine HIV rapid test kits to develop a national HIV testing algorithm in Nigeria

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Orji Bassey

2015-05-01

Full Text Available Background: Non-cold chain-dependent HIV rapid testing has been adopted in many resource-constrained nations as a strategy for reaching out to populations. HIV rapid test kits (RTKs have the advantage of ease of use, low operational cost and short turnaround times. Before 2005, different RTKs had been used in Nigeria without formal evaluation. Between 2005 and 2007, a study was conducted to formally evaluate a number of RTKs and construct HIV testing algorithms. Objectives: The objectives of this study were to assess and select HIV RTKs and develop national testing algorithms. Method: Nine RTKs were evaluated using 528 well-characterised plasma samples. These comprised 198 HIV-positive specimens (37.5% and 330 HIV-negative specimens (62.5%, collected nationally. Sensitivity and specificity were calculated with 95% confidence intervals for all nine RTKs singly and for serial and parallel combinations of six RTKs; and relative costs were estimated. Results: Six of the nine RTKs met the selection criteria, including minimum sensitivity and specificity (both ≥ 99.0% requirements. There were no significant differences in sensitivities or specificities of RTKs in the serial and parallel algorithms, but the cost of RTKs in parallel algorithms was twice that in serial algorithms. Consequently, three serial algorithms, comprising four test kits (BundiTM, DetermineTM, Stat-Pak® and Uni-GoldTM with 100.0% sensitivity and 99.1% – 100.0% specificity, were recommended and adopted as national interim testing algorithms in 2007. Conclusion: This evaluation provides the first evidence for reliable combinations of RTKs for HIV testing in Nigeria. However, these RTKs need further evaluation in the field (Phase II to re-validate their performance.

The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm.

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Derryck B Klarkowski

Full Text Available BACKGROUND: Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT (two positive RDTs alone for HIV diagnosis used in voluntary counselling and testing (VCT sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. METHODOLOGY/PRINCIPAL FINDINGS: 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2 and UniGold HIV rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm HIV confirmation test (OIC-HIV. Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2. 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3-6.7 when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9-99.9% with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. CONCLUSIONS: The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV

Accuracy in HIV Rapid Testing among Laboratory and Non-laboratory Personnel in Zambia: Observations from the National HIV Proficiency Testing System.

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Sheila Mwangala

Full Text Available Despite rapid task-shifting and scale-up of HIV testing services in high HIV prevalence countries, studies evaluating accuracy remain limited. This study aimed to assess overall accuracy level and factors associated with accuracy in HIV rapid testing in Zambia.Accuracy was investigated among rural and urban HIV testing sites participating in two annual national HIV proficiency testing (PT exercises conducted in 2009 (n = 282 sites and 2010 (n = 488 sites. Testers included lay counselors, nurses, laboratory personnel and others. PT panels of five dry tube specimens (DTS were issued to testing sites by the national reference laboratory (NRL. Site accuracy level was assessed by comparison of reported results to the expected results. Non-parametric rank tests and multiple linear regression models were used to assess variation in accuracy between PT cycles and between tester groups, and to examine factors associated with accuracy respectively.Overall accuracy level was 93.1% (95% CI: 91.2-94.9 in 2009 and 96.9% (95% CI: 96.1-97.8 in 2010. Differences in accuracy were seen between the tester groups in 2009 with laboratory personnel being more accurate than non-laboratory personnel, while in 2010 no differences were seen. In both PT exercises, lay counselors and nurses had more difficulties interpreting results, with more occurrences of false-negative, false-positive and indeterminate results. Having received the standard HIV rapid testing training and adherence to the national HIV testing algorithm were positively associated with accuracy.The study showed an improvement in tester group and overall accuracy from the first PT exercise to the next. Average number of incorrect test results per 1000 tests performed was reduced from 69 to 31. Further improvement is needed, however, and the national HIV proficiency testing system seems to be an important tool in this regard, which should be continued and needs to be urgently strengthened.

Evaluation of a rapid test for HIV antibodies in saliva and blood ...

African Journals Online (AJOL)

Objective. To test whole blood and saliva for HIV antibodies (anti-HIV) using a rapid test strip capillary flow . immunoassay, and to correlate the test strip results with blood specimen results obtained from routine diagnostic antiHIV assays. Design. A prospective pilot study of selected HIV-positive and HIV-negative individuals ...

Addressing unmet need for HIV testing in emergency care settings: a role for computer-facilitated rapid HIV testing?

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Kurth, Ann E; Severynen, Anneleen; Spielberg, Freya

2013-08-01

HIV testing in emergency departments (EDs) remains underutilized. The authors evaluated a computer tool to facilitate rapid HIV testing in an urban ED. Randomly assigned nonacute adult ED patients were randomly assigned to a computer tool (CARE) and rapid HIV testing before a standard visit (n = 258) or to a standard visit (n = 259) with chart access. The authors assessed intervention acceptability and compared noted HIV risks. Participants were 56% nonWhite and 58% male; median age was 37 years. In the CARE arm, nearly all (251/258) of the patients completed the session and received HIV results; four declined to consent to the test. HIV risks were reported by 54% of users; one participant was confirmed HIV-positive, and two were confirmed false-positive (seroprevalence 0.4%, 95% CI [0.01, 2.2]). Half (55%) of the patients preferred computerized rather than face-to-face counseling for future HIV testing. In the standard arm, one HIV test and two referrals for testing occurred. Computer-facilitated HIV testing appears acceptable to ED patients. Future research should assess cost-effectiveness compared with staff-delivered approaches.

evaluation of a rapid test for hiv antibodies in saliva and blood

African Journals Online (AJOL)

To test whole blood and saliva for HIV antibodies. (anti-HIV) using a rapid test strip capillary flow . immunoassay ... Design. A prospective pilot study of selected HIV-positive and ... defined by the underlying illness or condition is illustrated in.

HIV rapid diagnostic testing by lay providers in a key population-led health service programme in Thailand.

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Wongkanya, Rapeeporn; Pankam, Tippawan; Wolf, Shauna; Pattanachaiwit, Supanit; Jantarapakde, Jureeporn; Pengnongyang, Supabhorn; Thapwong, Prasopsuk; Udomjirasirichot, Apichat; Churattanakraisri, Yutthana; Prawepray, Nanthika; Paksornsit, Apiluk; Sitthipau, Thidadaow; Petchaithong, Sarayut; Jitsakulchaidejt, Raruay; Nookhai, Somboon; Lertpiriyasuwat, Cheewanan; Ongwandee, Sumet; Phanuphak, Praphan; Phanuphak, Nittaya

2018-01-01

Introduction:  Rapid diagnostic testing (RDT) for HIV has a quick turn-around time, which increases the proportion of people testing who receive their result. HIV RDT in Thailand has traditionally been performed only by medical technologists (MTs), which is a barrier to its being scaled up. We evaluated the performance of HIV RDT conducted by trained lay providers who were members of, or worked closely with, a group of men who have sex with men (MSM) and with transgender women (TG) communities, and compared it to tests conducted by MTs. Methods:  Lay providers received a 3-day intensive training course on how to perform a finger-prick blood collection and an HIV RDT as part of the Key Population-led Health Services (KPLHS) programme among MSM and TG. All the samples were tested by lay providers using Alere Determine HIV 1/2. HIV-reactive samples were confirmed by DoubleCheckGold Ultra HIV 1&2 and SD Bioline HIV 1/2. All HIV-positive and 10% of HIV-negative samples were re-tested by MTs using Serodia HIV 1/2. Results:  Of 1680 finger-prick blood samples collected and tested using HIV RDT by lay providers in six drop-in centres in Bangkok, Chiang Mai, Chonburi and Songkhla, 252 (15%) were HIV-positive. MTs re-tested these HIV-positive samples and 143 randomly selected HIV-negative samples with 100% concordant test results. Conclusion:  Lay providers in Thailand can be trained and empowered to perform HIV RDT as they were found to achieve comparable results in sample testing with MTs. Based on the task-shifting concept, this rapid HIV testing performed by lay providers as part of the KPLHS programme has great potential to enhance HIV prevention and treatment programmes among key at-risk populations.

A cross-sectional survey of attitudes to HIV risk and rapid HIV testing among clients of sex workers in Switzerland.

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Darling, Katharine E A; Diserens, Esther-Amélie; N'garambe, Chantal; Ansermet-Pagot, Anne; Masserey, Eric; Cavassini, Matthias; Bodenmann, Patrick

2012-10-01

To assess attitudes to HIV risk and acceptability of rapid HIV testing among clients of street-based female sex workers (FSW) in Lausanne, Switzerland, where HIV prevalence in the general population is 0.4%. The authors conducted a cross-sectional study in the red light district of Lausanne for five nights in September of 2008, 2009 and 2010. Clients of FSW were invited to complete a questionnaire in the street assessing demographic characteristics, attitudes to HIV risk and HIV testing history. All clients interviewed were then offered anonymous finger stick rapid HIV testing in a van parked on-site. The authors interviewed 112, 127 and 79 clients in 2008, 2009 and 2010, respectively. All were men, average age 32-37 years old; 40-60% were in a stable relationship. History of unprotected sex was higher with non-commercial partners (33-50%) than with FSW (6-11%); 29-46% of clients had never undergone an HIV test. Anonymous rapid HIV testing was accepted by 45-50% of clients. Out of 109 HIV tests conducted during the three study periods, none was reactive. On-site HIV counselling and testing is acceptable among clients of FSW in this urban setting. These individuals represent an unquantified population, a proportion of which has an incomplete understanding of HIV risk in the face of high-risk behaviour, with implications for potential onward transmission to non-commercial sexual partners.

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

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Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

2016-06-01

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

The cost of implementing rapid HIV testing in sexually transmitted disease clinics in the United States.

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Eggman, Ashley A; Feaster, Daniel J; Leff, Jared A; Golden, Matthew R; Castellon, Pedro C; Gooden, Lauren; Matheson, Tim; Colfax, Grant N; Metsch, Lisa R; Schackman, Bruce R

2014-09-01

Rapid HIV testing in high-risk populations can increase the number of persons who learn their HIV status and avoid spending clinic resources to locate persons identified as HIV infected. We determined the cost to sexually transmitted disease (STD) clinics of point-of-care rapid HIV testing using data from 7 public clinics that participated in a randomized trial of rapid testing with and without brief patient-centered risk reduction counseling in 2010. Costs included counselor and trainer time, supplies, and clinic overhead. We applied national labor rates and test costs. We calculated median clinic start-up costs and mean cost per patient tested, and projected incremental annual costs of implementing universal rapid HIV testing compared with current testing practices. Criteria for offering rapid HIV testing and methods for delivering nonrapid test results varied among clinics before the trial. Rapid HIV testing cost an average of US $22/patient without brief risk reduction counseling and US $46/patient with counseling in these 7 clinics. Median start-up costs per clinic were US $1100 and US $16,100 without and with counseling, respectively. Estimated incremental annual costs per clinic of implementing universal rapid HIV testing varied by whether or not brief counseling is conducted and by current clinic testing practices, ranging from a savings of US $19,500 to a cost of US $40,700 without counseling and a cost of US $98,000 to US $153,900 with counseling. Universal rapid HIV testing in STD clinics with same-day results can be implemented at relatively low cost to STD clinics, if brief risk reduction counseling is not offered.

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

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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.

Acceptability of rapid oral fluid HIV testing among male injection drug users in Taiwan, 1997 and 2007.

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Lyu, Shu-Yu; Morisky, Donald E; Yeh, Ching-Ying; Twu, Shiing-Jer; Peng, Eugene Yu-Chang; Malow, Robert M

2011-04-01

Rapid oral fluid HIV testing (rapid oral testing) is in the process of being adapted in Taiwan and elsewhere given its advantages over prior HIV testing methods. To guide this process, we examined the acceptability of rapid oral testing at two time points (i.e., 1997 and 2007) among one of the highest risk populations, male injection drug users (IDUs). For this purpose, an anonymous self-administered survey was completed by HIV-negative IDUs involved in the criminal justice system in 1997 (N (1)=137 parolees) and 2007 (N (2)=106 prisoners). A social marketing model helped guide the design of our questionnaire to assess the acceptability of rapid oral testing. This included assessing a new product, across four marketing dimensions: product, price, promotion, and place. Results revealed that in both 1997 and 2007, over 90% indicated that rapid oral testing would be highly acceptable, particularly if the cost was under US$6, and that a pharmacy would be the most appropriate and accessible venue for selling the rapid oral testing kits. The vast majority of survey respondents believed that the cost of rapid oral testing should be federally subsidized and that television and newspaper advertisements would be the most effective media to advertise for rapid oral testing. Both the 1997 and 2007 surveys suggested that rapid oral HIV testing would be particularly accepted in Taiwan by IDUs after release from the criminal justice system.

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

International Nuclear Information System (INIS)

White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

2014-01-01

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

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White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

2014-07-15

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

Evaluation du test rapide oral aware™ omt HIV 1/2 pour le ...

African Journals Online (AJOL)

Chaque participant a fourni un échantillon de fluide oral pour la réalisation du test Aware™ OMT HIV-1/2 et du sang testé suivant l'algorithme séquentiel de tests ELISAs Murex® HIV-1.2.0 (Laboratoires Abbott, Japon) et Test ELISA peptidique maison du CeDReS. Résultats : la sensibilité, la spécificité, la Valeur Prédictive ...

Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

Directory of Open Access Journals (Sweden)

Andrew Mujugira

Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.

[The social marketing models and policy advices for HIV rapid testing initiated by non-govermental organization].

Science.gov (United States)

Liu, H; Cai, L P; Xue, H; Zhao, Y; Wu, D; Zhang, D P; Yin, W Y; Sun, J P

2016-10-06

Currently, a growing number of community-based organizations are providing rapid HIV testing service in various forms, some people with specific needs also purchase HIV rapid test papers through online sales channels, those imply that the demand of HIV self-test is in increasing year by year.In this paper, aims to understand the current situation of HIV rapid test led by CBOs and the approach, strategies and results of social marketing by means of expert interviews and site visits. Hope to illustrate the current situation, and make recommendations for future work.

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study.

Directory of Open Access Journals (Sweden)

Augustine T Choko

2015-09-01

Full Text Available Home-based HIV testing and counselling (HTC achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST. The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test to adult (≥16 y old residents (n = 16,660 and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover residents self-tested during months 1-12, with adolescents (16-19 y most likely to test. 10,614/14,004 (75.8% participants shared results with volunteer-counsellors. Of 1,257 (11.8% HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3% newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159-426. HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo, with fewer (7.3%, 95% CI 6.8%-7.8% positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2% of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4% remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1

Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.

Science.gov (United States)

Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter; Bricault, Christine A; Liu, Po-Ting; Boyd, Michael; Kirilova, Marinela; Mercado, Noe B; Nanayakkara, Ovini S; Vrbanac, Vladimir D; Tager, Andrew M; Larocca, Rafael A; Seaman, Michael S; Barouch, Dan H

2018-04-01

Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Copyright © 2018 Badamchi-Zadeh et al.

Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry.

Science.gov (United States)

Meng, Juncai; Lai, Ming-Tain; Munshi, Vandna; Grobler, Jay; McCauley, John; Zuck, Paul; Johnson, Eric N; Uebele, Victor N; Hermes, Jeffrey D; Adam, Gregory C

2015-06-01

HIV-1 protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. To identify novel PR inhibitors, a label-free, high-throughput mass spectrometry (HTMS) assay was developed using the RapidFire platform and applied as an orthogonal assay to confirm hits identified in a fluorescence resonance energy transfer (FRET)-based primary screen of > 1 million compounds. For substrate selection, a panel of peptide substrates derived from natural processing sites for PR was evaluated on the RapidFire platform. As a result, KVSLNFPIL, a new substrate measured to have a ~ 20- and 60-fold improvement in k cat/K m over the frequently used sequences SQNYPIVQ and SQNYPIV, respectively, was identified for the HTMS screen. About 17% of hits from the FRET-based primary screen were confirmed in the HTMS confirmatory assay including all 304 known PR inhibitors in the set, demonstrating that the HTMS assay is effective at triaging false-positives while capturing true hits. Hence, with a sampling rate of ~7 s per well, the RapidFire HTMS assay enables the high-throughput evaluation of peptide substrates and functions as an efficient tool for hits triage in the discovery of novel PR inhibitors. © 2015 Society for Laboratory Automation and Screening.

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons

DEFF Research Database (Denmark)

Kamara, David A; Nielsen, Lene Ryom; Ross, Michael

2014-01-01

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90ml/min/1.73m2 (using Cockcroft Gault) in the Data...

HIV-1 and HIV-2 infections in Guinea-Bissau, West Africa : studies of immune responses, prevailing viruses and epidemiological trends

OpenAIRE

Andersson, Sören

1999-01-01

This thesis encompasses immunological, virological and epidemiological studies of HIV-1 and HIV-2 infections in Guinea-Bissau. We have established a robust and reliable diagnostic strategy based on a combination of enzyme-linked immunosorbent assays (ELISAs) and rapid simple tests. Evaluations showed that the strategy had a high capacity to discriminate between HIV-1 and HIV-2 and a high concordance with polymerase chain reaction (PCR) testing. Epidemiological studies in...

Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides

Directory of Open Access Journals (Sweden)

Li Yun-Yao

2002-11-01

Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.

An advanced BLT-humanized mouse model for extended HIV-1 cure studies.

Science.gov (United States)

Lavender, Kerry J; Pace, Craig; Sutter, Kathrin; Messer, Ronald J; Pouncey, Dakota L; Cummins, Nathan W; Natesampillai, Sekar; Zheng, Jim; Goldsmith, Joshua; Widera, Marek; Van Dis, Erik S; Phillips, Katie; Race, Brent; Dittmer, Ulf; Kukolj, George; Hasenkrug, Kim J

2018-01-02

Although bone marrow, liver, thymus (BLT)-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: evaluate the GVHD-resistant C57 black 6 (C57BL/6) recombination activating gene 2 (Rag2)γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. Determine whether TKO-BLT mice could be maintained on antiretroviral therapy (ART) for extended periods of time. Assess the rapidity of viral rebound following therapy interruption. TKO-BLT mice were HIV-1 infected, treated with various ART regimens over extended periods of time and assayed for viral rebound following therapy interruption. Daily subcutaneous injection and oral ART-mediated suppression of HIV-1 infection was tested at various doses in TKO-BLT mice. Mice were monitored for suppression of viremia and cellular HIV-1 RNA and DNA prior to and following therapy interruption. Mice remained healthy for 45 weeks posthumanization and could be treated with ART for up to 18 weeks. Viremia was suppressed to less than 200 copies/ml in the majority of mice with significant reductions in cellular HIV-1 RNA and DNA. Treatment interruption resulted in rapid viral recrudescence. HIV-1 latency can be maintained in TKO-BLT mice over extended periods on ART and rapid viral rebound occurs following therapy removal. The additional 15-18 weeks of healthy longevity compared with other BLT models provides sufficient time to examine the decay kinetics of the latent reservoir as well as observe delays in recrudescence in HIV-1 cure studies.

Rapid Detection of Human Immunodeficiency Virus Types 1 and 2 by Use of an Improved Piezoelectric Biosensor

Science.gov (United States)

Severns, Virginia; Branch, Darren W.; Edwards, Thayne L.; Larson, Richard S.

2013-01-01

Disasters can create situations in which blood donations can save lives. However, in emergency situations and when resources are depleted, on-site blood donations require the rapid and accurate detection of blood-borne pathogens, including human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Techniques such as PCR and antibody capture by an enzyme-linked immunosorbent assay (ELISA) for HIV-1 and HIV-2 are precise but time-consuming and require sophisticated equipment that is not compatible with emergency point-of-care requirements. We describe here a prototype biosensor based on piezoelectric materials functionalized with specific antibodies against HIV-1 and HIV-2. We show the rapid and accurate detection of HIV-1 and HIV-2 in both simple and complex solutions, including human serum, and in the presence of a cross-confounding virus. We report detection limits of 12 50% tissue culture infective doses (TCID50s) for HIV-1 and 87 TCID50s for HIV-2. The accuracy, precision of measurements, and operation of the prototype biosensor compared favorably to those for nucleic acid amplification. We conclude that the biosensor has significant promise as a successful point-of-care diagnostic device for use in emergency field applications requiring rapid and reliable testing for blood-borne pathogens. PMID:23515541

Toward Automating HIV Identification: Machine Learning for Rapid Identification of HIV-Related Social Media Data.

Science.gov (United States)

Young, Sean D; Yu, Wenchao; Wang, Wei

2017-02-01

"Social big data" from technologies such as social media, wearable devices, and online searches continue to grow and can be used as tools for HIV research. Although researchers can uncover patterns and insights associated with HIV trends and transmission, the review process is time consuming and resource intensive. Machine learning methods derived from computer science might be used to assist HIV domain experts by learning how to rapidly and accurately identify patterns associated with HIV from a large set of social data. Using an existing social media data set that was associated with HIV and coded by an HIV domain expert, we tested whether 4 commonly used machine learning methods could learn the patterns associated with HIV risk behavior. We used the 10-fold cross-validation method to examine the speed and accuracy of these models in applying that knowledge to detect HIV content in social media data. Logistic regression and random forest resulted in the highest accuracy in detecting HIV-related social data (85.3%), whereas the Ridge Regression Classifier resulted in the lowest accuracy. Logistic regression yielded the fastest processing time (16.98 seconds). Machine learning can enable social big data to become a new and important tool in HIV research, helping to create a new field of "digital HIV epidemiology." If a domain expert can identify patterns in social data associated with HIV risk or HIV transmission, machine learning models could quickly and accurately learn those associations and identify potential HIV patterns in large social data sets.

Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

Directory of Open Access Journals (Sweden)

Xianxun Chi

Full Text Available The vast majority of people living with human immunodeficiency virus type 1 (HIV-1 have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

HIV rapid testing in the framework of an STI prevention project on a cohort of vulnerable Italians and immigrants.

Science.gov (United States)

Uccella, Ilaria; Petrelli, Alessio; Vescio, Maria Fenicia; De Carolis, Silvia; Fazioli, Cecilia; Pezzotti, Patrizio; Rezza, Gianni

2017-08-01

Uptake of HIV tests is a challenging issue in vulnerable populations including immigrants, normally using standard diagnostic tools. Objectives of this study were to evaluate the acceptability of HIV rapid test; estimate the percentage of newly HIV diagnoses and evaluate knowledge, attitudes and perception (KAP) about HIV/AIDS and other STIs in a specific set of immigrants and vulnerable population in Rome (Italy). All immigrant and Italian people, aged 16-70 years, attending the infectious disease outpatient clinic of the National Institute for Health, Migration and Poverty (INMP) in Rome (Italy), during the period December 2012 to December 2013 were enrolled. HIV rapid testing was provided for free and patients were asked to fill in a questionnaire evaluating KAP about HIV/STIs. All patients with risky sexual behaviours or with a recent diagnosis of STIs were invited to come back after 3-6 months and a post-counselling questionnaire was offered. Out of the total sample, 99.2% (n = 825) accepted the "rapid test" and 10 new HIV diagnoses were found (1.22%; 95% CI 0.58%-2.22%). Three hundred and eighty-five participants (47%) answered the entry questionnaire and 58 (15%) completed the follow-up. Overall, we found high knowledge about HIV/AIDS; however, lower educational level and immigrant status were associated with poor knowledge about HIV, other STIs and prevention methods. Immigrants have lower perception of sexual risk and higher prejudice than Italians. Our study showed high acceptance of rapid test in this specific vulnerable population and this allowed to identify new HIV diagnoses in unaware people. Socioeconomic inequalities observed in the KAP questionnaire suggest the need for actions to support the reduction of cultural differences in knowledge of HIV/AIDS and for policies aimed at improving access to health services and preventions programmes of marginalized populations.

[Benefits of using rapid HIV testing at the PMU-FLON walk-in clinic in Lausanne].

Science.gov (United States)

Gilgien, W; Aubert, J; Bischoff, T; Herzig, L; Perdrix, J

2012-05-16

Lab tests are frequently used in primary care to guide patient care. This is particularly the case when a severe disorder, or one that will affect patients' initial care, needs to be excluded rapidly. At the PMU-FLON walk-in clinic the use of HIV testing as recommended by the Swiss Office of Public Health was hampered by the delay in obtaining test results. This led us to introduce rapid HIV testing which provides results within 30 minutes. Following the first 250 tests the authors discuss the results as well as the benefits of rapid HIV testing in an urban walk-in clinic.

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.

Repeat confirmatory testing for persons with discordant whole blood and oral fluid rapid HIV test results: findings from post marketing surveillance.

Science.gov (United States)

Wesolowski, Laura G; Mackellar, Duncan A; Ethridge, Steven F; Zhu, Julia H; Owen, S Michele; Sullivan, Patrick S

2008-02-06

Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB), immunofluorescent assay (IFA) or approved nucleic acid amplification test (NAAT)). When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result), repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results. Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing. Of 167,371 rapid tests conducted, 2589 (1.6%) were reactive: of these, 2417 (93%) had positive WB/IFA, 172 (7%) had negative or indeterminate WB/IFA. Of 89/172 (52%) persons with a repeat confirmatory test: 17 (19%) were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81%) were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative) (ptest [adjusted OR 2.6, 95% CI (1.3, 4.9)]. Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for persons with discordant results. Because of the lower sensitivity of oral fluid WBs, confirmatory testing following a reactive rapid test should be conducted using serum or plasma, when possible.

HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.

Science.gov (United States)

Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

2011-04-15

Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

Back to the future: revisiting HIV-1 lethal mutagenesis

Science.gov (United States)

Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

2012-01-01

The concept of eliminating HIV-1 infectivity by elevating the viral mutation rate was first proposed over a decade ago, even though the general concept had been conceived earlier for RNA viruses. Lethal mutagenesis was originally viewed as a novel chemotherapeutic approach for treating HIV-1 infection in which use of a viral mutagen would over multiple rounds of replication lead to the lethal accumulation of mutations, rendering the virus population non infectious – known as the slow mutation accumulation model. There have been limitations in obtaining good efficacy data with drug leads, leaving some doubt into clinical translation. More recent studies of the APOBEC3 proteins as well as new progress in the use of nucleoside analogs for inducing lethal mutagenesis have helped to refocus attention on rapid induction of HIV-1 lethal mutagenesis in a single or limited number of replication cycles leading to a rapid mutation accumulation model. PMID:23195922

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

Science.gov (United States)

Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems

Science.gov (United States)

Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Forthal, Donald; Mao, Lingjun; -Abanto, Segundo Hernandez; Urban, Lori; Landucci, Gary; Fischer, Rainer; Jiang, Xiaoming

2013-01-01

Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production. PMID:23533588

Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

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Yvonne Rosenberg

Full Text Available Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT of simian/human immunodeficiency virus (SHIV in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01 or a single chain antibody construct (m9, for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production.

Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB study

DEFF Research Database (Denmark)

Bjerrum, Stephanie; Kenu, Ernest; Lartey, Margaret

2015-01-01

BACKGROUND: Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy. METHODS: HIV-infected adults eligible...

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...

Electronic vending machines for dispensing rapid HIV self-testing kits: a case study.

Science.gov (United States)

Young, Sean D; Klausner, Jeffrey; Fynn, Risa; Bolan, Robert

2014-02-01

This short report evaluates the feasibility of using electronic vending machines for dispensing oral, fluid, rapid HIV self-testing kits in Los Angeles County. Feasibility criteria that needed to be addressed were defined as: (1) ability to find a manufacturer who would allow dispensing of HIV testing kits and could fit them to the dimensions of a vending machine, (2) ability to identify and address potential initial obstacles, trade-offs in choosing a machine location, and (3) ability to gain community approval for implementing this approach in a community setting. To address these issues, we contracted a vending machine company who could supply a customized, Internet-enabled machine that could dispense HIV kits and partnered with a local health center available to host the machine onsite and provide counseling to participants, if needed. Vending machines appear to be feasible technologies that can be used to distribute HIV testing kits.

Knowledge of HIV and willingness to conduct oral rapid HIV testing among dentists in Xi'an China.

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Lirong Wang

Full Text Available China is considered a country of low HIV prevalence (780,000 people living with HIV, however, HIV infections among high-risk populations continue to grow at alarming rates. Voluntary Counseling and Testing services were first implemented in 2003, and oral rapid HIV testing (ORHT began in 2012. Dentists, as oral health experts, would be well placed to conduct ORHT. We assessed willingness of dentists to undertake ORHT in their clinical practice.A cross-sectional, paper-based survey of dentists from the Xi'an region of China was conducted from April to June 2013. Dentists were recruited from Shaanxi Stomatological Association using a stratified sampling methodology. A 40-item survey was used to measure knowledge of HIV, attitudes toward people living with HIV and willingness to conduct ORHT.477 dentists completed the survey with a mean HIV knowledge test score of 13.2/18 (SD 1.9. If made available in the dental setting, 276 (57.9% preferred to use blood to diagnose HIV, only 190 (39.8% preferred saliva or both. Four hundred and thirty-five (91.2% thought that ORHT was needed in dental clinics. Female dentists felt more accepting of ORHT than males (93.8% vs. 87.8%; χ2=5.145; p<0.05. 42.6% of the participants who responded thought that lack of education on ORHT for dentists was the most urgent problem to solve for ORHT, 144 (31.3% thought that lack of support for ORHT from patients was the most urgent problem. There was statistically significant difference among dental hospital, dentistry and department of dentistry (χ2=24.176; p<0.05.The majority of Chinese dentists thought that ORHT was needed in the dental setting. Providing opportunities for dentists and dental students to learn about HIV testing guidelines and practices is needed as well as feasibility and implementation science research.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

Science.gov (United States)

Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.; Siliciano, Robert F.

2016-01-01

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID:27382129

DEPIVIH 2: Use of three HIV testing methods in French primary care settings - ELISA laboratory screening versus two rapid point-of-care HIV tests.

Science.gov (United States)

Papadima, D; Gauthier, R; Prévoteau du Clary, F; Bouée, S; Conort, G; Livrozet, J-M; Taulera, O; Wajsbrot, A; Majerholc, C; Peter, J-M; Aubert, J-P

2018-03-01

The primary endpoint was to evaluate the use of HIV testing methods by French primary care providers: Elisa laboratory screening, instant result HIV diagnostic test and rapid result HIV diagnostic test. The secondary endpoints were the population screening rate of unknown HIV status consulting during the study period, reasons for screening and for choosing the specific screening method, the investigators' satisfaction with the rapid diagnostic test (RDT) and problems encountered. National prospective interventional study with French family physicians (FP) from December 2013 to December 2014. FPs enrolled all consenting adults consulting for an HIV screening test during a 6-month period: the choice was an Elisa laboratory test or one of the two RDTs. During the study period, 43 FPs included 981 patients. HIV screening was performed for the first time for 31.6% of patients; 767 (78.2%) Elisa laboratory test prescriptions and 214 (21.8%) RDTs were performed, leading to a screening rate of 1.3%. For 120 (15.7%) of the Elisa laboratory tests, the result was not reported and six RDTs were not valid. Nine patients were diagnosed as HIV-infected (0.9%): five with Elisa laboratory test and four with RDT. Almost 90% of FPs were willing to keep on using RDTs in their daily practice. In general practice, RDTs may be an important additional tool to traditional HIV screening. They could account for one in five tests prescribed in this context. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

THE PREVALENCE OF HUMAN IMMUNODEFIENCY VIRUS-1 (HIV-1 SUBTYPES AND TRANSMISSION METHOD AMONG HIV/AIDS INFECTION PATIENT IN TULUNGAGUNG, EAST JAVA INDONESIA

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Achmad Ardianto

2015-05-01

Full Text Available The rapid epidemic growth of HIV is continuing in Indonesia. There are some factors which have influenced the spreading of this epidemic in Indonesia, such as the poor awareness to avoid unsafe free sex attitude and the sharing of needles and syringes among intravenous drug users (IDUs. The sexual transmission of HIV has also apparently increased in Tulungagung. Commercial sex workers play a significant role in the spread of HIV in Tulungagung. People in Tulungagung have worked at other countries as Indonesian migrants. This condition can cause the increase number of HIV-1 case and the possibility of genetic variation (subtype HIV-1 in Tulungagung. This research is aimed to analyze the subtype and to determine estimation of transmission mode on infected patient of HIV-1 and AIDS who came to Seruni clinic Dr. Iskak hospital in Tulungagung. 40 HIV?AIDSpatients were interviewed to determine the subtype and the transmission mode. The results showed that 14 of 40 plasma samples (35% were successfully to amplified and sequenced. OverallCRF01-AE wereidentified as predominant subtype among HIV/AIDS patients in Tulungagung. Based on individual information, 31 of 40 subjects (77% were heterosexual transmission.

Rapid Immuno-Chromatographic Assay for the Detection of Antibodies to HIV Compare with Elisa among Voluntary and Replacement Blood Donor of Mymensingh Medical College Hospital.

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Chakrabarty, P; Rudra, S; Hossain, M A; Begum, S A; Mirza, T T; Rudra, M

2015-04-01

Suitable algorithms based on a combination of two or more simple rapid HIV assays have been shown to have a diagnostic accuracy comparable to double enzyme-linked immunosorbent assay (ELISA) or double ELISA with Western Blot strategies. The aims of this study were to evaluate the performance of five simple rapid HIV assays using whole blood samples from voluntary and replacement blood donors & HIV-infected patients (positive samples from BSMMU, Dhaka). Five rapid HIV assays: Determine™ HIV-1/2 (Inverness Medical), SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), First Response HIV Card 1-2.0 (PMC Medical India Pvt Ltd.), HIV1/2 Stat-Pak Dipstick (Chembio Diagnostic System, Inc) and Uni-Gold™ HIV-1/2 (Biotech) were evaluated between 1st February to 30th June, 2013 using 400 whole blood samples from voluntary and replacement blood donors. All samples that were reactive on all or any of the five rapid assays and 10% of non-reactive samples were tested on a confirmatory Inno-Lia HIV I/II immunoblot assay (Immunogenetics). Only 01 sample including ten positive samples from BSMMU were confirmed HIV-1 antibody positive, while 399 were HIV negative. The sensitivity at initial testing of Determine, SD Bioline and Uni-Gold™ was 100% (95% CI; 99.1-100) while First Response and Stat-Pak had sensitivity of 99.5% (95% CI; 98.2-99.9) and 97.7% (95% CI; 95.7-98.9) respectively, which increased to 100% (95% CI; 99.1-100) on repeat testing. The initial specificity of the Uni-Gold™ assay was 100% (95% CI; 99.6-100) while specificities were 99.6% (95% CI; 99-99.9), 99.4% (95% CI; 98.8-99.7), 99.6% (95% CI; 99-99.9) and 99.8% (95% CI; 99.3-99.9) for Determine, SD Bioline, First Response and Stat-Pak assays, respectively. There was no any sample which was concordantly false positive in Uni-Gold™, Determine and SD Bioline assays. An alternative confirmatory HIV testing strategy based on initial testing on either SD Bioline or Determine assays followed by testing of reactive

Detection of hepatitis C virus (HCV among health care providers in an Egyptian university hospital: different diagnostic modalities

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El-Sokkary RH

2017-10-01

Full Text Available Rehab H El-Sokkary,1 Rehab M Elsaid Tash,1 Takwa E Meawed,1 Omnia S El Seifi,2 Eman M Mortada2 1Medical Microbiology and Immunology Department, 2Community, Environmental and Occupational Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt Background: Hepatitis C virus (HCV infection has received much attention and is placed at the core of the infection control agenda. It is considered as a major public health problem in Egypt, where the highest prevalence of HCV exists. The great risk of exposure to infection of health care providers (HCPs has highlighted the urgent need for implementing an infection control program. Objective: The purpose of this study was to detect the prevalence of HCV infection among HCPs in Zagazig University Hospitals and to assess the performance of different diagnostic modalities.Methodology: Blood, polymerase chain reaction (PCR, enzyme-linked immunosorbent assay (ELISA, and saliva tests were performed in enrolled HCPs.Results: This study compared HCV diagnosis Hepanostika HCV Ultra ELISA as a screening test and PCR as gold standard test, which resulted in 40.6% positive results by ELISA compared to 34.8% by PCR (p<0.0001, while OraQuick HCV rapid antibody compared to PCR shows that 37.7% of the participants were positive by OraQuick HCV rapid antibody test. Application of standard precautions while dealing with blood has negative significant correlation with HCV infection (rs=–0.265, p=0.03.Conclusion: HCPs at Zagazig University Hospitals are at high risk for HCV infection. Lack of compliance and awareness of prevention and control of the infection are associated cofactors. Serum HCV-Ab detection by Hepanostika HCV Ultra ELISA and OraQuick HCV rapid antibody test are sensitive and specific serologic assays for diagnosis with correspondent results to that obtained by quantitative real-time PCR. Keywords: HCV, ROC curve, OraQuick HCV, infection control

HIV-1 transmission linkage in an HIV-1 prevention clinical trial

Energy Technology Data Exchange (ETDEWEB)

Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

2009-01-01

HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. 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, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

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Ole S Søgaard

2015-09-01

Full Text Available Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03. Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04. Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2 were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.clinicaltrials.gov NTC02092116.

Low-cost HIV-1 diagnosis and quantification in dried blood spots by real time PCR.

Science.gov (United States)

Mehta, Nishaki; Trzmielina, Sonia; Nonyane, Bareng A S; Eliot, Melissa N; Lin, Rongheng; Foulkes, Andrea S; McNeal, Kristina; Ammann, Arthur; Eulalievyolo, Vindu; Sullivan, John L; Luzuriaga, Katherine; Somasundaran, Mohan

2009-06-05

Rapid and cost-effective methods for HIV-1 diagnosis and viral load monitoring would greatly enhance the clinical management of HIV-1 infected adults and children in limited-resource settings. Recent recommendations to treat perinatally infected infants within the first year of life are feasible only if early diagnosis is routinely available. Dried blood spots (DBS) on filter paper are an easy and convenient way to collect and transport blood samples. A rapid and cost effective method to diagnose and quantify HIV-1 from DBS is urgently needed to facilitate early diagnosis of HIV-1 infection and monitoring of antiretroviral therapy. We have developed a real-time LightCycler (rtLC) PCR assay to detect and quantify HIV-1 from DBS. HIV-1 RNA extracted from DBS was amplified in a one-step, single-tube system using primers specific for long-terminal repeat sequences that are conserved across all HIV-1 clades. SYBR Green dye was used to quantify PCR amplicons and HIV-1 RNA copy numbers were determined from a standard curve generated using serially diluted known copies of HIV-1 RNA. This assay detected samples across clades, has a dynamic range of 5 log(10), and %CV real-time systems demonstrated similar performance. The accuracy, reliability, genotype inclusivity and affordability, along with the small volumes of blood required for the assay suggest that the rtLC DBS assay will be useful for early diagnosis and monitoring of pediatric HIV-1 infection in resource-limited settings.

HIV Rapid Testing in a VA Emergency Department Setting: Cost Analysis at 5 Years.

Science.gov (United States)

Knapp, Herschel; Chan, Kee

2015-07-01

To conduct a comprehensive cost-minimization analysis to comprehend the financial attributes of the first 5 years of an implementation wherein emergency department (ED) registered nurses administered HIV oral rapid tests to patients. A health science research implementation team coordinated with ED stakeholders and staff to provide training, implementation guidelines, and support to launch ED registered nurse-administered HIV oral rapid testing. Deidentified quantitative data were gathered from the electronic medical records detailing quarterly HIV rapid test rates in the ED setting spanning the first 5 years. Comprehensive cost analyses were conducted to evaluate the financial impact of this implementation. At 5 years, a total of 2,620 tests were conducted with a quarterly mean of 131 ± 81. Despite quarterly variability in testing rates, regression analysis revealed an average increase of 3.58 tests per quarter. Over the course of this implementation, Veterans Health Administration policy transitioned from written to verbal consent for HIV testing, serving to reduce the time and cost(s) associated with the testing process. Our data indicated salient health outcome benefits for patients with respect to the potential for earlier detection, and associated long-run cost savings. Copyright © 2015. Published by Elsevier Inc.

Field evaluation of a dual rapid diagnostic test for HIV infection and syphilis in Lima, Peru.

Science.gov (United States)

Bristow, Claire C; Leon, Segundo R; Huang, Emily; Brown, Brandon J; Ramos, Lourdes B; Vargas, Silver K; Flores, Juan A; Caceres, Carlos F; Klausner, Jeffrey D

2016-05-01

Screening for HIV and syphilis in key populations is recommended by the WHO to reduce the morbidity, mortality and transmission associated with undiagnosed and untreated infections. Rapid point-of-care tests that can detect multiple infections with a single fingerprick whole blood specimen using a single device are gaining popularity. We evaluated the field performance of a rapid dual HIV and syphilis test in people at high risk of HIV and syphilis infections. Participants included men who have sex with men and transgender women recruited in Lima, Peru. Reference standard testing for detection of HIV and syphilis infections, conducted using blood samples from venipuncture, included Treponema pallidum particle agglutination and fourth-generation HIV enzyme immunoassay for which positive results had a confirmation HIV Western blot test. For the evaluation test, SD BIOLINE HIV/Syphilis Duo test (Standard Diagnostics, Korea), a fingerprick blood specimen was used. Sensitivity and specificity were calculated and the exact binomial method was used to determine 95% CIs. A total of 415 participants were recruited for the study. The dual test sensitivity for detection of T. pallidum infection was 89.2% (95% CI 83.5% to 93.5%) and specificity 98.8% (95% CI 96.5% to 99.8%). For detection of HIV infection, the sensitivity of the dual test was 99.1% (95% CI 94.8% to 100%) and specificity 99.4% (95% CI 97.7% to 99.9%). This high performing dual test should be considered for the use in clinical settings to increase uptake of simultaneous testing of HIV and syphilis and accelerate time to treatment for those who need it. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Repeat confirmatory testing for persons with discordant whole blood and oral fluid rapid HIV test results: findings from post marketing surveillance.

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Laura G Wesolowski

Full Text Available BACKGROUND: Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB, immunofluorescent assay (IFA or approved nucleic acid amplification test (NAAT. When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result, repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results. METHODOLOGY: Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing. PRINCIPAL FINDINGS: Of 167,371 rapid tests conducted, 2589 (1.6% were reactive: of these, 2417 (93% had positive WB/IFA, 172 (7% had negative or indeterminate WB/IFA. Of 89/172 (52% persons with a repeat confirmatory test: 17 (19% were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81% were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative (p<0.001 and having an initial oral fluid WB (vs. serum (p<0.001. Persons who had male-female sex (vs. male-male sex were at increased risk for not having a repeat test [adjusted OR 2.6, 95% CI (1.3, 4.9]. CONCLUSIONS: Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for

Epidemiological networks and drug resistance of HIV type 1 in Krasnoyarsk region, Russia

NARCIS (Netherlands)

Rumyantseva, Olga A.; Olkhovskiy, Igor A.; Malysheva, Marina A.; Ruzaeva, Ludmila A.; Vasiliev, Alexander V.; Kazennova, Elena V.; Bobkova, Marina R.; Lukashov, Vladimir V.

2009-01-01

To study the molecular epidemiology of HIV-1 in Krasnoyarsk region, Russia, where HIV-1 has spread rapidly since 2000, we obtained pol sequences from individuals living in this region (n = 67) as well as in the geographically closely related Altay region (n = 13). In both regions, subtype A viruses

Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau

DEFF Research Database (Denmark)

Sørensen, Allan; Jespersen, Sanne; Katzenstein, Terese L

2016-01-01

HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Sim~ao Mendes in Guinea......-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive...... antigen. Conclusion: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major...

Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania.

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Fabian C Franzeck

Full Text Available BACKGROUND: Co-infection with hepatitis B virus (HBV is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg before initiation of combination antiretroviral therapy (cART is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. METHODS: Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. RESULTS: Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47, 169/272 (63% subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439. HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0% subjects. Of these, 7/25 (28% were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6% and specificity at 100% (95% CI, 98.9-100%. Antibodies to HCV (anti-HCV were found in 10/272 (3.7%, 95% CI 2.0-6.4% of patients. CONCLUSION: This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.

μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

International Nuclear Information System (INIS)

Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

2003-01-01

A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3 + lymphoblasts and CD14 + monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients.

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Hønge, Bl; Jespersen, S; Medina, C; Té, Ds; da Silva, Zj; Ostergaard, L; Laursen, Al; Wejse, C; Krarup, H; Erikstrup, C

2014-10-01

In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation. © 2014 British HIV Association.

A gp41-based heteroduplex mobility assay provides rapid and accurate assessment of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission Pairs.

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Manigart, Olivier; Boeras, Debrah I; Karita, Etienne; Hawkins, Paulina A; Vwalika, Cheswa; Makombe, Nathan; Mulenga, Joseph; Derdeyn, Cynthia A; Allen, Susan; Hunter, Eric

2012-12-01

A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to both partners' amplicons separately (autologous) and as a mixture (heterologous). If the diversity between gp41 sequences was low (<5%), a homoduplex was observed upon gel electrophoresis and the transmission was characterized as having occurred between partners (linked). If a new heteroduplex formed, within the heterologous migration, the transmission was determined to be unlinked. Initial blind validation of gp-41 HMA demonstrated 90% concordance between HMA and sequencing with 100% concordance in the case of linked transmissions. Following validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated prospectively using both HMA and nucleotide sequences. Concordant results were obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and feasible tool to detect linked transmissions in the field. All identified unlinked results should be confirmed by sequence analyses.

Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

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Schmechel, S C; Russell, N; Hladik, F; Lang, J; Wilson, A; Ha, R; Desbien, A; McElrath, M J

2001-11-01

Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa.

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Ziningi Jaya

between 64.4% (CI: 44%- 84% and 89.2% (CI: 74%- 100%.Ten out of eleven of the clinics were rated as moderate (70-89%. All clinic have scored highest for the following audit component: equipment; process control and specimen management; and facility ad safety, with 100%. Clinics obtained the lowest scores for the assessment audit component followed by process improvement and organisation, with 40.9% (CI: 15.7-66.1%, 45.5% (CI: 10.4-80.5% and 56.8% (CI: 31.8 81.8%, respectively. A statistically significant correlation was observed between the following: category of staff performing the HIV rapid tests in the audited clinics and service and satisfactory audit component; weekly average number of patients using the audited PHC clinics and service and satisfactory audit component; number of HIV lay counsellors in the audited clinics and quality control audit component with p<0.05.In the small audit of primary healthcare clinics located within the rural part of KwaZulu-Natal, results revealed an overall moderate rating of the quality management system for rapid HIV testing. Improvements in the organisation, quality control, process improvement and assessment components could enable a higher quality assurance rating for rural HIV testing in KwaZulu-Natal.

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa.

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Jaya, Ziningi; Drain, Paul K; Mashamba-Thompson, Tivani P

2017-01-01

: 44%- 84%) and 89.2% (CI: 74%- 100%).Ten out of eleven of the clinics were rated as moderate (70-89%). All clinic have scored highest for the following audit component: equipment; process control and specimen management; and facility ad safety, with 100%. Clinics obtained the lowest scores for the assessment audit component followed by process improvement and organisation, with 40.9% (CI: 15.7-66.1%), 45.5% (CI: 10.4-80.5%) and 56.8% (CI: 31.8 81.8%), respectively. A statistically significant correlation was observed between the following: category of staff performing the HIV rapid tests in the audited clinics and service and satisfactory audit component; weekly average number of patients using the audited PHC clinics and service and satisfactory audit component; number of HIV lay counsellors in the audited clinics and quality control audit component with paudit of primary healthcare clinics located within the rural part of KwaZulu-Natal, results revealed an overall moderate rating of the quality management system for rapid HIV testing. Improvements in the organisation, quality control, process improvement and assessment components could enable a higher quality assurance rating for rural HIV testing in KwaZulu-Natal.

Phylodynamics of the HIV-1 epidemic in Cuba.

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Delatorre, Edson; Bello, Gonzalo

2013-01-01

Previous studies have shown that the HIV-1 epidemic in Cuba displayed a complex molecular epidemiologic profile with circulation of several subtypes and circulating recombinant forms (CRF); but the evolutionary and population history of those viral variants remains unknown. HIV-1 pol sequences of the most prevalent Cuban lineages (subtypes B, C and G, CRF18_cpx, CRF19_cpx, and CRFs20/23/24_BG) isolated between 1999 and 2011 were analyzed. Maximum-likelihood analyses revealed multiple introductions of subtype B (n≥66), subtype C (n≥10), subtype G (n≥8) and CRF18_cpx (n≥2) viruses in Cuba. The bulk of HIV-1 infections in this country, however, was caused by dissemination of a few founder strains probably introduced from North America/Europe (clades B(CU-I) and B(CU-II)), east Africa (clade C(CU-I)) and central Africa (clades G(CU), CRF18(CU) and CRF19(CU)), or locally generated (clades CRFs20/23/24_BG). Bayesian-coalescent analyses show that the major HIV-1 founder strains were introduced into Cuba during 1985-1995; whereas the CRFs_BG strains emerged in the second half of the 1990s. Most HIV-1 Cuban clades appear to have experienced an initial period of fast exponential spread during the 1990s and early 2000s, followed by a more recent decline in growth rate. The median initial growth rate of HIV-1 Cuban clades ranged from 0.4 year⁻¹ to 1.6 year⁻¹. Thus, the HIV-1 epidemic in Cuba has been a result of the successful introduction of a few viral strains that began to circulate at a rather late time of the AIDS pandemic, but then were rapidly disseminated through local transmission networks.

HIV-1 Drug Resistance Mutations Among Antiretroviral-Naïve HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

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Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Kantipong, Pacharee; Lee, Christopher K. C.; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G.; Phanuphak, Praphan

2011-01-01

(See editorial commentary by Jordan on pages 1058–1060.) Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. PMID:21460324

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

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Diserens, Esther-Amélie; Bodenmann, Patrick; N'Garambe, Chantal; Ansermet-Pagot, Anne; Vannotti, Marco; Masserey, Eric; Cavassini, Matthias

2010-03-19

Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

The spread and effect of HIV-1 infection in sub-Saharan Africa.

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Buvé, Anne; Bishikwabo-Nsarhaza, Kizito; Mutangadura, Gladys

2002-06-08

Africa is the continent most severely affected by the global HIV-1 epidemic, with east and southern Africa in general more severely affected than west and central Africa. Differences in the spread of the epidemic can be accounted for by a complex interplay of sexual behaviour and biological factors that affect the probability of HIV-1 transmission per sex act. Sexual behaviour patterns are determined by cultural and socioeconomic contexts. In sub-Saharan Africa, some traditions and socioeconomic developments have contributed to the extensive spread of HIV-1 infection, including the subordinate position of women, impoverishment and decline of social services, rapid urbanisation and modernisation, and wars and conflicts. Populations in many parts of Africa are becoming trapped in a vicious circle as the HIV-1 epidemic leads to high mortality rates in young and economically productive age groups, and thus leads to further impoverishment. Interventions to control HIV-1 should not only target individuals, but also aim to change those aspects of cultural and socioeconomic context that increase the vulnerability to HIV-1 of people and communities.

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : the D:A:D study

NARCIS (Netherlands)

Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J; Schölvinck, Elisabeth H.

2014-01-01

BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

NARCIS (Netherlands)

Kamara, David A.; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Brandt, R. Salbøl; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundström, A.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.

2014-01-01

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

NARCIS (Netherlands)

Kamara, D.A.; Ryom, L.; Ross, M.; Kirk, O.; Reiss, P.; Morlat, P.; Moranne, O.; Fux, C.A.; Mocroft, A.; Sabin, C.; Lundgren, J.D.; Smith, C.J.; Koopmans †, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van; et al.,

2014-01-01

BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

Conserved hydrogen bonds and water molecules in MDR HIV-1 protease substrate complexes

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Liu, Zhigang [Wayne State Univ., Detroit, MI (United States); Case Western Reserve Univ., Cleveland, OH (United States); Harbor Hospital Baltimore, MD (United States); Wang, Yong [Wayne State Univ., Detroit, MI (United States); Yedidi, Ravikiran S. [Wayne State Univ., Detroit, MI (United States); National Institutes of Health, Bethesda, MD (United States); Dewdney, Tamaria G. [Wayne State Univ., Detroit, MI (United States); Reiter, Samuel J. [Wayne State Univ., Detroit, MI (United States); Brunzelle, Joseph S. [Northwestern Univ. Feinberg School of Medicine, Chicago, IL (United States); Kovari, Iulia A. [Wayne State Univ., Detroit, MI (United States); Kovari, Ladislau C. [Wayne State Univ., Detroit, MI (United States)

2012-12-19

Success of highly active antiretroviral therapy (HAART) in anti-HIV therapy is severely compromised by the rapidly developing drug resistance. HIV-1 protease inhibitors, part of HAART, are losing their potency and efficacy in inhibiting the target. Multi-drug resistant (MDR) 769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, 90) was selected for the present study to understand the binding to its natural substrates. The nine crystal structures of MDR769 HIV-1 protease substrate hepta-peptide complexes were analyzed in order to reveal the conserved structural elements for the purpose of drug design against MDR HIV-1 protease. Our structural studies demonstrated that highly conserved hydrogen bonds between the protease and substrate peptides, together with the conserved crystallographic water molecules, played a crucial role in the substrate recognition, substrate stabilization and protease stabilization. Additionally, the absence of the key flap-ligand bridging water molecule might imply a different catalytic mechanism of MDR769 HIV-1 protease compared to that of wild type (WT) HIV-1 protease.

A Peptide Derived from the HIV-1 gp120 Coreceptor-Binding Region Promotes Formation of PAP248-286 Amyloid Fibrils to Enhance HIV-1 Infection.

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Jinquan Chen

Full Text Available Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.Here, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2, can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM, in the presence or absence of EP2. Circular dichroism (CD spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells.Nanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection.

GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

Energy Technology Data Exchange (ETDEWEB)

Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.; Delino, Nicole S.; Nakata, Hirotomo; Venkateswara Rao, Kalapala; Ghosh, Arun K.; Mitsuya, Hiroaki

2017-09-25

We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510 emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.

Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

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Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

2001-12-01

The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

Comparison of patient comprehension of rapid HIV pre-test fundamentals by information delivery format in an emergency department setting

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Clark Melissa A

2007-09-01

Full Text Available Abstract Background Two trials were conducted to compare emergency department patient comprehension of rapid HIV pre-test information using different methods to deliver this information. Methods Patients were enrolled for these two trials at a US emergency department between February 2005 and January 2006. In Trial One, patients were randomized to a no pre-test information or an in-person discussion arm. In Trial Two, a separate group of patients were randomized to an in-person discussion arm or a Tablet PC-based video arm. The video, "Do you know about rapid HIV testing?", and the in-person discussion contained identical Centers for Disease Control and Prevention-suggested pre-test information components as well as information on rapid HIV testing with OraQuick®. Participants were compared by information arm on their comprehension of the pre-test information by their score on a 26-item questionnaire using the Wilcoxon rank-sum test. Results In Trial One, 38 patients completed the no-information arm and 31 completed the in-person discussion arm. Of these 69 patients, 63.8% had twelve years or fewer of formal education and 66.7% had previously been tested for HIV. The mean score on the questionnaire for the in-person discussion arm was higher than for the no information arm (18.7 vs. 13.3, p ≤ 0.0001. In Trial Two, 59 patients completed the in-person discussion and 55 completed the video arms. Of these 114 patients, 50.9% had twelve years or fewer of formal education and 68.4% had previously been tested for HIV. The mean score on the questionnaire for the video arm was similar to the in-person discussion arm (20.0 vs. 19.2; p ≤ 0.33. Conclusion The video "Do you know about rapid HIV testing?" appears to be an acceptable substitute for an in-person pre-test discussion on rapid HIV testing with OraQuick®. In terms of adequately informing ED patients about rapid HIV testing, either form of pre-test information is preferable than for patients

Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

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Marc C Levesque

2009-07-01

Full Text Available The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+ T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells.In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis.Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

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Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L; Sanders, Eduard J; Peshu, Norbert M; Krieger, John N; Muller, Charles H; Coombs, Robert W; Fredricks, David N; Graham, Susan M

2017-03-01

HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

[Introduction of rapid syphilis and HIV testing in prenatal care in Colombia: qualitative analysis].

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Ochoa-Manjarrés, María Teresa; Gaitán-Duarte, Hernando Guillermo; Caicedo, Sidia; Gómez, Berta; Pérez, Freddy

2016-12-01

Interpret perceptions of Colombian health professionals concerning factors that obstruct and facilitate the introduction of rapid syphilis and HIV testing in prenatal care services. A qualitative study based on semi-structured interviews was carried out. A convenience sample was selected with 37 participants, who included health professionals involved in prenatal care services, programs for pregnant women, clinical laboratories, and directors of health care units or centers, as well as representatives from regional departments and the Ministry of Health. Colombia does not do widespread screening with rapid syphilis and HIV tests in prenatal care. The professionals interviewed stated they did not have prior experience in the use of rapid tests-except for laboratory staff-or in the course of action in response to a positive result. The insurance system hinders access to timely diagnosis and treatment. Health authorities perceive a need to review existing standards, strengthen the first level of care, and promote comprehensive prenatal care starting with contracts between insurers and health service institutional providers. Participants recommended staff training and integration between health-policymaking and academic entities for updating training programs. The market approach and the characteristics of the Colombian health system constitute the main barriers to implementation of rapid testing as a strategy for elimination of mother-to-child transmission of syphilis and HIV. Measures identified include making changes in contracts between insurers and health service institutional providers, adapting the timing and duration of prenatal care procedures, and training physicians and nurses involved in prenatal care.

Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing.

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Dieter Hoffmann

Full Text Available Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART, particularly in resource-limited settings. Non-nucleoside reverse trancriptase inhibitor (NNRTI-based regimens with an NRTI backbone containing lamivudine (3TC or emtricitabine (FTC are preferred first ART regimens. Failure with these drug combinations typically involves the selection of NNRTI- and/or 3TC/FTC-resistant viruses. Therefore, the availability of simple assays to measure both types of drug resistance is critical. We have developed a high throughput screening test for assessing enzymatic resistance of the HIV-1 RT in plasma to 3TC/FTC and NNRTIs. The test uses the sensitive "Amp-RT" assay with a newly-developed real-time PCR format to screen biochemically for drug resistance in single reactions containing either 3TC-triphosphate (3TC-TP or nevirapine (NVP. Assay cut-offs were defined based on testing a large panel of subtype B and non-subtype B clinical samples with known genotypic profiles. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. We further demonstrate the utility of an HIV capture method in plasma by using magnetic beads coated with CD44 antibody that eliminates the need for ultracentifugation. Thus our results support the use of this simple approach for distinguishing WT from NNRTI- or 3TC/FTC-resistant viruses in clinical samples. This enzymatic testing is subtype-independent and can assist in the clinical management of diverse populations particularly in resource-limited settings.

HIV-1 vaccines

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Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

2014-01-01

The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

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DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

2018-04-11

Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M�

Feasibility of implementing rapid oral fluid HIV testing in an urban University Dental Clinic: a qualitative study

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Hutchinson M

2012-05-01

Full Text Available Abstract Background More than 1 million individuals in the U.S. are infected with HIV; approximately 20% of whom do not know they are infected. Early diagnosis of HIV infection results in earlier access to treatment and reductions in HIV transmission. In 2006, the CDC recommended that health care providers offer routine HIV screening to all adolescent and adult patients, regardless of community seroprevalence or patient lifestyle. Dental providers are uniquely positioned to implement these recommendations using rapid oral fluid HIV screening technology. However, thus far, uptake into dental practice has been very limited. Methods The study utilized a qualitative descriptive approach with convenience samples of dental faculty and students. Six in-depth one-on-one interviews were conducted with dental faculty and three focus groups were conducted with fifteen dental students. Results Results were fairly consistent and indicated relatively high levels of acceptability. Barriers and facilitators of oral fluid HIV screening were identified in four primary areas: scope of practice/practice enhancement, skills/knowledge/training, patient service/patient reactions and logistical issues. Conclusions Oral fluid HIV screening was described as having benefits for patients, dental practitioners and the public good. Many of the barriers to implementation that were identified in the study could be addressed through training and interdisciplinary collaborations.

Pregnancy and HIV infection

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Mete Sucu; Cihan Cetin; Mehmet Ozsurmeli; Ghanim Khatib; Ceren Cetin; Cuneyt Evruke

2016-01-01

The management of Human Immunodeficiency Virus (HIV) infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinician...

Trans-dissemination of exosomes from HIV-1-infected cells fosters both HIV-1 trans-infection in resting CD4+ T lymphocytes and reactivation of the HIV-1 reservoir.

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Chiozzini, Chiara; Arenaccio, Claudia; Olivetta, Eleonora; Anticoli, Simona; Manfredi, Francesco; Ferrantelli, Flavia; d'Ettorre, Gabriella; Schietroma, Ivan; Andreotti, Mauro; Federico, Maurizio

2017-09-01

Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4 + T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4 + T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4 + T lymphocytes. Here, we report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4 + T lymphocytes, which appears stronger with mature than immature DCs. Using purified preparations of both HIV-1 and exosomes, we observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4 + T lymphocytes induces efficient trans-infection and HIV-1 expression in target cells. Most relevant, when both mDCs and CD4 + T lymphocytes were isolated from combination anti-retroviral therapy (ART)-treated HIV-1-infected patients, trans-dissemination of exosomes from HIV-1-infected cells led to HIV-1 reactivation from the viral reservoir. In sum, our data suggest a role of exosome trans-dissemination in both HIV-1 spread in the infected host and reactivation of the HIV-1 reservoir.

Computer-facilitated rapid HIV testing in emergency care settings: provider and patient usability and acceptability.

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Spielberg, Freya; Kurth, Ann E; Severynen, Anneleen; Hsieh, Yu-Hsiang; Moring-Parris, Daniel; Mackenzie, Sara; Rothman, Richard

2011-06-01

Providers in emergency care settings (ECSs) often face barriers to expanded HIV testing. We undertook formative research to understand the potential utility of a computer tool, "CARE," to facilitate rapid HIV testing in ECSs. Computer tool usability and acceptability were assessed among 35 adult patients, and provider focus groups were held, in two ECSs in Washington State and Maryland. The computer tool was usable by patients of varying computer literacy. Patients appreciated the tool's privacy and lack of judgment and their ability to reflect on HIV risks and create risk reduction plans. Staff voiced concerns regarding ECS-based HIV testing generally, including resources for follow-up of newly diagnosed people. Computer-delivered HIV testing support was acceptable and usable among low-literacy populations in two ECSs. Such tools may help circumvent some practical barriers associated with routine HIV testing in busy settings though linkages to care will still be needed.

Stepping toward a Macaque Model of HIV-1 Induced AIDS

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Jason T. Kimata

2014-09-01

Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

Developing strategies for HIV-1 eradication

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Durand, Christine M.; Blankson, Joel N.; Siliciano, Robert F.

2014-01-01

Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication, transforming the outlook for infected patients. However, reservoirs of replication-competent forms of the virus persist during HAART, and when treatment is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1 latency, as well as a report that HIV-1 infection was eradicated in one individual, have renewed interest in finding a cure for HIV-1 infection. Strategies for HIV-1 eradication include gene therapy and hematopoietic stem cell transplantation, stimulating host immunity to control HIV-1 replication, and targeting latent HIV-1 in resting memory CD4+ T cells. Future efforts should aim to provide better understanding of how to reconstitute the CD4+ T cell compartment with genetically engineered cells, exert immune control over HIV-1 replication, and identify and eliminate all viral reservoirs. PMID:22867874

Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1–Seropositive Kenyan Men

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Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L.; Sanders, Eduard J.; Peshu, Norbert M.; Krieger, John N.; Muller, Charles H.; Coombs, Robert W.; Fredricks, David N.; Graham, Susan M.

2017-01-01

Introduction: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. Methods: We analyzed semen samples from 42 HIV-1–seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Results: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: −0.77, 95% CI: −1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Conclusion: Most of these HIV-1–infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission. PMID:27861240

Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population.

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Peters, Philip J; Westheimer, Emily; Cohen, Stephanie; Hightow-Weidman, Lisa B; Moss, Nicholas; Tsoi, Benjamin; Hall, Laura; Fann, Charles; Daskalakis, Demetre C; Beagle, Steve; Patel, Pragna; Radix, Asa; Foust, Evelyn; Kohn, Robert P; Marmorino, Jenni; Pandori, Mark; Fu, Jie; Samandari, Taraz; Gay, Cynthia L

2016-02-16

Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Number and proportion with acute HIV infections detected. Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both

Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples

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MUGO, Nelly R.; HEFFRON, Renee; DONNELL, Deborah; WALD, Anna; WERE, Edwin O.; REES, Helen; CELUM, Connie; KIARIE, James N.; COHEN, Craig R.; KAYINTEKORE, Kayitesi; BAETEN, Jared M.

2011-01-01

Background Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results 3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR 2.31, 95% CI 1.22–4.39). This effect was not attenuated in adjusted analysis (adjusted HR 2.47, 95% CI 1.26–4.85). Conclusions HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. PMID:21785321

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+ T cell responses in HIV-1-infected individuals.

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Núria Climent

Full Text Available Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B in human monocyte-derived dendritic cells (MDDC and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α. MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Human macrophages support persistent transcription from unintegrated HIV-1 DNA

International Nuclear Information System (INIS)

Kelly, Jeremy; Beddall, Margaret H.; Yu Dongyang; Iyer, Subashini R.; Marsh, Jon W.; Wu Yuntao

2008-01-01

Retroviruses require integration of their RNA genomes for both stability and productive viral replication. In HIV infection of non-dividing, resting CD4 T cells, where integration is greatly impeded, the reverse transcribed HIV DNA has limited biological activity and a short half-life. In metabolically active and proliferating T cells, unintegrated DNA rapidly diminishes with cell division. HIV also infects the non-dividing but metabolically active macrophage population. In an in vitro examination of HIV infection of macrophages, we find that unintegrated viral DNA not only has an unusual stability, but also maintains biological activity. The unintegrated linear DNA, 1-LTR, and 2-LTR circles are stable for at least 30 days. Additionally, there is persistent viral gene transcription, which is selective and skewed towards viral early genes such as nef and tat with highly diminished rev and vif. One viral early gene product Nef was measurably synthesized. We also find that independent of integration, the HIV infection process in macrophages leads to generation of numerous chemokines

Hyperthermia stimulates HIV-1 replication.

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Ferdinand Roesch

Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

Oral rapid test: an alternative to traditional HIV screening in Chile

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Lisette Paola Irarrazábal

2013-06-01

Full Text Available OBJECTIVE: To compare the sensitivity and specificity of an Oral Rapid Test (ORT to that of the Enzyme-Linked Immunosorbent Assay (ELISA for HIV testing in Santiago, Chile; to track the number of study participants returning for ELISA testing results; and to analyze the participants' perceptions of the ORT compared to the ELISA. METHODS: A total of 497 people were recruited in Santiago, Chile: 153 had previously tested positive for HIV, and 344 were of unknown status. Participants were tested for HIV using both the ELISA and the ORT to examine and compare specificity and sensitivity. Qualitative data were collected from 22 participants to compare perceptions of the testing experience with ORT versus ELISA. RESULTS: The ELISA reported 184 (37% of the 497 participants as being "positive" for HIV antibodies; the ORT showed 181 (36.4% as being "reactive" for HIV. The ORT showed a sensitivity of 98.4% (95.7%-99.9%, 95% Confidence Interval and specificity of 100%. The Kappa test produced K = 0.983 (P < 0.0001. Of the 344 participants whose HIV status was unknown at the start of the study, 55 failed to return for their ELISA results. Participants positively perceived ORT as having reduced both waiting time and anxiety over obtaining their test results. ORT oral swabbing appeared more practical and less invasive than drawing blood for the ELISA. CONCLUSIONS: The ORT and ELISA were statistically equal in specificity and sensitivity. ORT provides quicker results, potentially ensuring that more people receive them, and does not require handling of or exposure to potentially hazardous blood products. Trial number: ClinicalTrials.gov identifier: NCT01733927.

Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

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Celum, Connie; Wald, Anna; Lingappa, Jairam R.; Magaret, Amalia S.; Wang, Richard S.; Mugo, Nelly; Mujugira, Andrew; Baeten, Jared M.; Mullins, James I.; Hughes, James P.; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, Myron; Were, Edwin; Fife, Kenneth H.; de Bruyn, Guy; Gray, Glenda E.; McIntyre, James A.; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinead; Rees, Helen; Vwalika, Bellington; Stevens, Wendy; Campbell, Mary S.; Thomas, Katherine K.; Coombs, Robert W.; Morrow, Rhoda; Whittington, William L.H.; McElrath, M. Juliana; Barnes, Linda; Ridzon, Renee; Corey, Lawrence

2010-01-01

BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ≥250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir

Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

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Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

2014-01-01

Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China.

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Lu, Xinli; Zhao, Cuiying; Wang, Wei; Nie, Chenxi; Zhang, Yuqi; Zhao, Hongru; Chen, Suliang; Cui, Ze

2016-01-01

Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P  0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.

Male Partner Risk Behaviors Are Associated With Reactive Rapid HIV Antibody Tests Among Pregnant Mexican Women: Implications for Prevention of Vertical and Sexual HIV Transmission in Concentrated HIV Epidemics.

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Rivero, Estela; Kendall, Tamil

2015-01-01

Mexico's policies on antenatal HIV testing are contradictory, and little is known about social and behavioral characteristics that increase pregnant Mexican women's risks of acquiring HIV. We analyzed the association between risk behaviors reported by pregnant women for themselves and their male partners, and women's rapid HIV antibody test results from a large national sample. Three quarters of pregnant women with a reactive test did not report risk behaviors for themselves and one third did not report risk behaviors for themselves or their male partners. In the retrospective case-control analysis, other than reporting multiple sexual partners, reactive pregnant women reported risk behaviors did not differ from nonreactive women's behaviors. However, reactive pregnant women were significantly more likely to have reported risk behaviors for male partners. Our findings support universal offer of antenatal HIV testing and suggest that HIV prevention for women should focus on reducing risk of HIV acquisition within stable relationships. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

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Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

2009-04-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

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Gretja Schnell

2009-04-01

Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

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Peretti, Silvia; Schiavoni, Ilaria; Pugliese, Katherina; Federico, Maurizio

2006-01-01

We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies

Psoralen/UV inactivation of HIV-1-infected cells for use in cytologic and immunologic procedures

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Watson, A.J.; Klaniecki, J.; Hanson, C.V.

1990-01-01

A rapid procedure for the inactivation of HIV-1-infected cells using psoralen and ultraviolet (UV) light is described. Exposure of HIV-1-infected cells to 5 micrograms/ml psoralen followed by UV irradiation (320-380 nm) for 5 minutes yields cells that are noninfectious as assessed by extended infectivity assays. The psoralen/UV inactivation procedure described is effective with cells chronically or acutely infected with HIV-1 and is unaffected by cell densities up to 12 x 10(6)/ml. At 5 micrograms/ml psoralen does little damage to cellular permeability as shown by the ability of treated cells to exclude trypan blue and propidium iodide. Psoralen/UV treatment of HIV-1-infected cells does not cause a significant decrease in the reactivity of HIV-1 core and envelope antigens or cellular antigens to monoclonal antibodies. Experiments are presented demonstrating the use of these cells for flow cytometry studies and for cell surface labeling using the lactoperoxidase 125 I iodination procedure

Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and HCV.

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Mohammadi-Yeganeh, S; Paryan, M; Mirab Samiee, S; Kia, V; Rezvan, H

2012-06-01

Developed in 1991, nucleic acid sequence-based amplification (NASBA) has been introduced as a rapid molecular diagnostic technique, where it has been shown to give quicker results than PCR, and it can also be more sensitive. This paper describes the development of a molecular beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in plasma samples. A well-conserved region in the HIV-1 pol gene and 5'-NCR of HCV genome were used for primers and molecular beacon design. The performance features of HCV/HIV-1 multiplex NASBA assay including analytical sensitivity and specificity, clinical sensitivity and clinical specificity were evaluated. The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was beacon probes detected all HCV genotypes and all major variants of HIV-1. This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

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2018-01-01

ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

Rapid testing may not improve uptake of HIV testing and same day results in a rural South African community: a cohort study of 12,000 women.

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Ntombizodumo B Mkwanazi

Full Text Available Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area.HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6% and 4,810 (74.6% agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4% requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p35 years (AOR 0.756, p<0.01 compared to those <20 years.Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given.

Identifying HIV-1 dual infections

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Cornelissen Marion

2007-09-01

Full Text Available Abstract Transmission of human immunodeficiency virus (HIV is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus and superinfections (second infection after a specific immune response to the first infecting strain has developed can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR strains could recombine to produce a pan-resistant, transmittable virus. We will describe in this review what is presently known about super- and re-infection among ambient viral infections, as well as the first cases of HIV-1 superinfection, including HIV-1 triple infections. The clinical implications, the impact of the immune system, and the effect of anti-retroviral therapy will be covered, as will as the timing of HIV superinfection. The methods used to detect HIV-1 dual infections will be discussed in detail. To increase the likelihood of detecting a dual HIV-1 infection, pre-selection of patients can be done by serotyping, heteroduplex mobility assays (HMA, counting the degenerate base codes in the HIV-1 genotyping sequence, or surveying unexpected increases in the

Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

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Bomsel, Morgane; Ganor, Yonatan

2017-12-01

The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

New approaches to design HIV-1 T-cell vaccines.

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Perrin, Hélène; Canderan, Glenda; Sékaly, Rafick-Pierre; Trautmann, Lydie

2010-09-01

Following the evidence that T-cell responses are crucial in the control of HIV-1 infection, vaccines targeting T-cell responses were tested in recent clinical trials. However, these vaccines showed a lack of efficacy. This review attempts to define the qualitative and quantitative features that are desirable for T-cell-induced responses by vaccines. We also describe strategies that could lead to achievement of this goal. Using the yellow fever vaccine as a benchmark of an efficient vaccine, recent studies identified factors of immune protection and more importantly innate immune pathways needed for the establishment of long-term protective adaptive immunity. To prevent or control HIV-1 infection, a vaccine must induce efficient and persistent antigen-specific T cells endowed with mucosal homing capacity. Such cells should have the capability to counteract HIV-1 diversity and its rapid spread from the initial site of infection. To achieve this goal, the activation of a diversified innate immune response is critical. New systems biology approaches will provide more precise correlates of immune protection that will pave the way for new approaches in T-cell-based vaccines.

HIV-1 Latency in Monocytes/Macrophages

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Amit Kumar

2014-04-01

Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines.

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Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel

2017-10-01

Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

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Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

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Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

2017-10-17

The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

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Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

2009-01-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.

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Daniëlle van Manen

Full Text Available BACKGROUND: AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years. To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODS: The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. RESULTS: Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. CONCLUSIONS: Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.

Genome-Wide Association Scan in HIV-1-Infected Individuals Identifying Variants Influencing Disease Course

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van Manen, Daniëlle; Delaneau, Olivier; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte D.; Limou, Sophie; Bol, Sebastiaan M.; Burger, Judith A.; Zwinderman, Aeilko H.; Moerland, Perry D.; van 't Slot, Ruben; Zagury, Jean-François; van 't Wout, Angélique B.; Schuitemaker, Hanneke

2011-01-01

Background AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methods The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Results Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Conclusions Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection. PMID:21811574

Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

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Mickaël J Ploquin

2016-08-01

Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

Pregnancy and HIV infection

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Mete Sucu

2016-12-01

Full Text Available The management of Human Immunodeficiency Virus (HIV infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinicians taking care of pregnants to have current information. Therefore, in our review we aimed to summarize the prenatal course, treatment and preventive methods for perinatal transmission of HIV. [Archives Medical Review Journal 2016; 25(4.000: 522-535

Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

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Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Fricke, Thomas [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Miccio, Annarita [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Valle-Casuso, Jose Carlos; Perez, Patricio [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Souque, Philippe [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Rizzi, Ermanno; Severgnini, Marco [Institute of Biomedical Technologies, CNR, Milano (Italy); Mavilio, Fulvio [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Genethon, Evry (France); Charneau, Pierre [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Diaz-Griffero, Felipe, E-mail: felipe.diaz-griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States)

2013-05-25

The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.

Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

International Nuclear Information System (INIS)

Di Nunzio, Francesca; Fricke, Thomas; Miccio, Annarita; Valle-Casuso, Jose Carlos; Perez, Patricio; Souque, Philippe; Rizzi, Ermanno; Severgnini, Marco; Mavilio, Fulvio; Charneau, Pierre; Diaz-Griffero, Felipe

2013-01-01

The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa

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Jaya, Ziningi; Drain, Paul K.; Mashamba-Thompson, Tivani P.

2017-01-01

Introduction Rapid HIV tests have improved access to HIV diagnosis and treatment by providing quick and convenient testing in rural clinics and resource-limited settings. In this study, we evaluated the quality management system for voluntary and provider-initiated point-of-care HIV testing in primary healthcare (PHC) clinics in rural KwaZulu-Natal (KZN), South Africa. Material and methods We conducted a quality assessment audit in eleven PHC clinics that offer voluntary HIV testing and couns...

Provider-related barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs) and hospitals.

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Bogart, Laura M; Howerton, Devery; Lange, James; Setodji, Claude Messan; Becker, Kirsten; Klein, David J; Asch, Steven M

2010-06-01

We examined provider-reported barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs), and hospitals. 12 primary metropolitan statistical areas (PMSAs; three per region) were sampled randomly, with sampling weights proportional to AIDS case reports. Across PMSAs, all 671 hospitals and a random sample of 738 clinics/CBOs were telephoned for a survey on rapid HIV test availability. Of the 671 hospitals, 172 hospitals were randomly selected for barriers questions, for which 158 laboratory and 136 department staff were eligible and interviewed in 2005. Of the 738 clinics/CBOs, 276 were randomly selected for barriers questions, 206 were reached, and 118 were eligible and interviewed in 2005-2006. In multivariate models, barriers regarding translation of administrative/quality assurance policies into practice were significantly associated with rapid HIV testing availability. For greater rapid testing diffusion, policies are needed to reduce administrative barriers and provide quality assurance training to non-laboratory staff.

Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

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Silvana Pasetto

Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India

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Maity Susmita

2012-11-01

Full Text Available Abstract Background HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. Results A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.; ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd. gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd., Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd. did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100% except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.. The kit efficiency didn’t vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p  Conclusions ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for

Acute HIV infection with rapid progression to AIDS

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Marcio de Oliveira Silva

Full Text Available Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

[Molecular epidemiological characteristics of HIV-1 strains isolated from newly diagnosed MSM subjects (2006-2010) in Beijing, China].

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Ye, Jing-Rong; Zang, Wan-Chun; Su, Xue-Li; Lu, Hong-Yan; Hao, Ming-Qiang; Xin, Ruo-Lei; Chen, Guo-Min; He, Xiong; Zeng, Yi

2014-03-01

This study aims to analyze the molecular epidemiological characteristics of HIV-1 strains prevailing among men who have sex with men (MSM) in Beijing, China. The pol gene fragments from 250 newly diagnosed HIV-1-infected MSM individuals during 2006-2010 in Beijing were amplified by RT-nested PCR, sequenced, and phylogenetically analyzed. HIV-1 pol gene from 189 individuals were amplified and analyzed; 81 (42. 9%), 3 (1. 6%), 2 (1.0%), 88 (46. 6%), and 15 (7.9%) individuals were infected with HIV-1 subtypes B, B', C, CRF01_AE, and CRF07_BC, respectively. The subtypes B and CRF01_AE could both be grouped into two clusters, and CRFO7_BC strains shared high homology and were presumed to originate from a common ancestor. The HIV-1 circulating in MSM in Beijing had a lower genetic diversity than in heterosexuals. The HIV-1 epidemic (2006-2010) in MSM in Beijing was actually a rapid spread of HIV-1 CRF01 AE and B, or rather native strains of the two viruses.

Cytoplasmic Dynein Promotes HIV-1 Uncoating

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Paulina Pawlica

2014-11-01

Full Text Available Retroviral capsid (CA cores undergo uncoating during their retrograde transport (toward the nucleus, and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating.

Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins.

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Morgane Rolland

Full Text Available BACKGROUND: While human immunodeficiency virus type 1 (HIV-1-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. CONCLUSIONS/SIGNIFICANCE: Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.

No evidence of association between HIV-1 and malaria in populations with low HIV-1 prevalence.

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Diego F Cuadros

Full Text Available The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in the western region of sub-Saharan Africa.Population-based cross-sectional data were obtained from the HIV/AIDS Demographic and Health Surveys conducted in Burkina Faso, Ghana, Guinea, Mali, Liberia and Cameroon, and the malaria atlas project. Using generalized linear mixed models, we assessed the relationship between HIV-1 and Plasmodium falciparum parasite rate (PfPR adjusting for important socio-economic and biological cofactors. We found no evidence that individuals living in areas with stable malaria transmission (PfPR>0.46 have higher odds of being HIV-positive than individuals who live in areas with PfPR≤0.46 in western sub-Saharan Africa (estimated odds ratio 1.14, 95% confidence interval 0.86-1.50. In contrast, the results suggested that PfPR was associated with being infected with HIV in Cameroon (estimated odds ratio 1.56, 95% confidence interval 1.23-2.00.Contrary to our previous research on eastern sub-Saharan Africa, this study did not identify an association between PfPR and infection with HIV in western sub-Saharan Africa, which suggests that malaria might not play an important role in the spread of HIV in populations where the HIV prevalence is low. Our work highlights the importance of understanding the epidemiologic effect of co-infection and the relevant

A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites

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Knezevich Anna

2007-05-01

Full Text Available Abstract HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.

Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

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Hammond Robert R

2004-05-01

Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

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

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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.

The anti-HIV-1 effect of scutellarin

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Zhang Gaohong; Wang Qian; Chen Jijun; Zhang Xuemei; Tam, S.-C.; Zheng Yongtang

2005-01-01

Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1 IIIB ), drug-resistant virus (HIV-1 74V ), and low-passage clinical isolated virus (HIV-1 KM018 ). From syncytia inhibition study, the EC 50 of scutellarin against HIV-1 IIIB direct infection in C8166 cells was 26 μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC 50 reduced to 15 μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-1 74V (EC 50 253 μM) and HIV-1 KM018 (EC 50 136 μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication

The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure.

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Ranganath, Nischal; Sandstrom, Teslin S; Burke Schinkel, Stephanie C; Côté, Sandra C; Angel, Jonathan B

2018-02-14

Cells latently infected with human immunodeficiency virus (HIV) evade immune- and drug-mediated clearance. These cells harbor intracellular signaling defects, including impairment of the antiviral type I interferon response. Such defects have also been observed in several cancers and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate cells latently infected with HIV-1, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in cell lines latently infected with HIV-1. Following this, a reduction in HIV-1 DNA and inducible HIV-1 replication was observed following MG1 infection of latently infected, resting CD4+ T cells generated using an in vitro model of latency. Last, MG1 infection resulted in a reduction in HIV-1 DNA and inducible HIV-1 replication in memory CD4+ T cells isolated from effectively treated, HIV-1-infected individuals. Our results therefore highlight a novel approach to eliminate the latent HIV-1 reservoir. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

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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

Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

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Gringeri, A; Santagostino, E; Muça-Perja, M; Mannucci, P M; Zagury, J F; Bizzini, B; Lachgar, A; Carcagno, M; Rappaport, J; Criscuolo, M; Blattner, W; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

Diagnostic accuracy and acceptability of rapid HIV oral testing among adults attending an urban public health facility in Kampala, Uganda.

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Joanita Nangendo

Full Text Available The prevalence of HIV in Uganda is 7.3%, and yet nearly 40% of people living with HIV are unaware of their status. The current HIV testing policy which is strictly blood-based poses several challenges including: a need for high level laboratory skills, stringent waste disposal needs, and painful sample collection. It is envisaged that introduction of a rapid, painless HIV oral fluid test as a potential alternative is likely to increase the number of people testing. The aim of this study was to determine the diagnostic accuracy and acceptability of rapid HIV oral testing among adults attending Kisenyi Health Centre IV in Kampala.We conducted a cross-sectional study among 440 adults recruited consecutively at Kisenyi Health Centre IV from January to March 2016. The diagnostic accuracy of the HIV oral test was assessed by comparing to the national HIV serial testing algorithm. We also assessed for acceptability among patients and health care workers (HCWs by triangulating responses from a structured questionnaire, three focus group discussions and seven key informant interviews. Acceptability was defined as willingness to take the test at the time of the study and intention for future use of the test if it was availed. The prevalence of HIV infection among study participants was 14.8%. The HIV oral fluid test was highly accurate with sensitivity of 100% (95% CI; 94.5-100.0, specificity of 100% (95% CI; 99.0-100.0, positive predictive value (PPV of 100% (95% CI; 94.5-100.0 and negative predictive value (NPV of 100% (95% CI; 99.0-100.0. Acceptability of HIV oral testing was also high at 87.0% (95% CI; 83.6-89.9. Participants preferred HIV oral testing because it was: pain free (91%, n = 399 and did not require blood draw (82%, n = 360.The HIV oral fluid test has high diagnostic accuracy and acceptability. HIV oral testing is a suitable addition to the national HIV testing strategies with the potential of increasing access to HIV testing services in

Dynamics of Preferential Substrate Recognition in HIV-1 Protease: Redefining the Substrate Envelope

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Özen, Ayşegül; Haliloğlu, Türkan; Schiffer, Celia A.

2011-01-01

HIV-1 protease (PR) permits viral maturation by processing the Gag and Gag-Pro-Pol polyproteins. Though HIV-1 PR inhibitors (PIs) are used in combination antiviral therapy, the emergence of drug resistance has limited their efficacy. The rapid evolution of HIV-1 necessitates the consideration of drug resistance in novel drug-design strategies. Drug-resistant HIV-1 PR variants, while no longer efficiently inhibited, continue to efficiently hydrolyze the natural viral substrates. Though highly diverse in sequence, the HIV-1 PR substrates bind in a conserved three-dimensional shape we defined as the “substrate envelope”. We previously showed that resistance mutations arise where PIs protrude beyond the substrate envelope, as these regions are crucial for drug binding but not for substrate recognition. Here, we extend this model by considering the role of protein dynamics in the interaction of HIV-1 PR with its substrates. Seven molecular dynamics simulations of PR-substrate complexes were performed to estimate the conformational flexibility of substrates in their complexes. Interdependency of the substrate-protease interactions may compensate for the variations in cleavage-site sequences, and explain how a diverse set of sequences can be recognized as substrates by the same enzyme. This diversity may be essential for regulating sequential processing of substrates. We also define a dynamic substrate envelope as a more accurate representation of PR-substrate interactions. This dynamic substrate envelope, described by a probability distribution function, is a powerful tool for drug design efforts targeting ensembles of resistant HIV-1 PR variants with the aim of developing drugs that are less susceptible to resistance. PMID:21762811

Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy

International Nuclear Information System (INIS)

Suzuki, Tatsunori; Yamamoto, Norio; Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke; Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki; Tanaka, Rie; Kato, Shingo; Aida, Yoko

2009-01-01

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin α, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin α interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin α interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

Sex, drugs, and HIV: rapid assessment of HIV risk behaviors among street-based drug using sex workers in Durban, South Africa.

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Needle, Richard; Kroeger, Karen; Belani, Hrishikesh; Achrekar, Angeli; Parry, Charles D; Dewing, Sarah

2008-11-01

South Africa is experiencing significant changes in patterns of illicit drug use, including increasing injection and non-injection drug use, and the use of drugs by persons engaged in sex work, both of which could further expand the HIV/AIDS epidemic. In 2005, a rapid ethnographic assessment was conducted in Durban, South Africa, to learn more about patterns of drug use and HIV risk behaviors among drug-using, street-based sex workers. Field teams recruited 52 current injection and non-injection drug users for key informant interviews and focus groups, and they conducted mapping and observation in identified high-risk neighborhoods. Key informants were offered free, voluntary counseling and HIV rapid testing. The results of the assessment indicate that in this population, drugs play an organizing role in patterns of daily activities, with sex work closely linked to the buying, selling, and using of drugs. Participants reported using multiple drugs including crack cocaine, heroin, Ecstasy and Mandrax, and their choices were based on their expectations about the functional role and behavioral and pharmacological properties of the drugs. The organization of sex work and patterns of drug use differ by gender, with males exercising more control over daily routines and drug and sexual transactions than females. Activities of female sex workers are subject to considerable control by individual pimps, many of whom also function as landlords and drug dealers. A strong hold over the overlapping economies of drugs and sex work by a few individuals extends to control of the physical and social settings in which sex is exchanged and drugs are sold and used as well as the terms under which sex work is carried out. The potential for accelerated HIV spread is considerable given the evidence of overlapping drug-using and sexual risk behaviors and the mixing patterns across drug and sexual risk networks.

HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

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Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

2015-08-01

Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on

Picomolar dichotomous activity of gnidimacrin against HIV-1.

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Li Huang

Full Text Available Highly active antiretroviral therapy (HAART has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Thus, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnane diterpene gnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel of HIV-1 R5 virus infection of peripheral blood mononuclear cells (PBMCs at an average concentration lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 ×4 virus infection of PBMCs. The strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its effect on down-regulation of the HIV-1 coreceptor CCR5. The anti-R5 virus activity of gnidimacrin was completely abrogated by a selective protein kinase C beta inhibitor enzastaurin, which suggests that protein kinase C beta plays a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. In summary, these results suggest that gnidimacrin could activate latent HIV-1, specifically kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations.

HIV-1 envelope glycoprotein

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Caulfield, Michael; Cupo, Albert; Dean, Hansi; Hoffenberg, Simon; King, C. Richter; Klasse, P. J.; Marozsan, Andre; Moore, John P.; Sanders, Rogier W.; Ward, Andrew; Wilson, Ian; Julien, Jean-Philippe

2017-08-22

The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

A cross sectional survey of the barriers for implementing rapid HIV testing among French general practitioners.

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Fraisse, Thibaut; Fourcade, Camille; Brazes-Sanz, Julie; Koumar, Yatrika; Lavigne, Jean Philippe; Sotto, Albert; Laureillard, Didier

2016-10-01

In France, almost 30,000 people are unaware of their HIV-positive status. Innovative screening strategies are essential to reach this population. The aim of this study was to describe the acceptability of rapid HIV testing (RHT) among French general practitioners (GPs) working in the south of France and barriers for implementing this strategy. We analysed an anonymous questionnaire sent by mail to GPs about demographic data, routine practice, knowledge of RHT and barriers to its use. Between 1 April and 30 September 2013, out of the 165 GPs contacted, 78 returned the questionnaires. The GPs' mean age was 52 years; 49 were men. Fifty-one GPs reported that their registered patients included at least one HIV-infected person and 70 GPs reported taking care of high-risk patients. Sixty-three percent of GPs reported being interested in using RHT in their daily practice. The main reasons reported by uninterested GPs were: greater confidence in standard HIV testing, difficulties including RHT during the routine consultation, difficulties to screen for other sexually transmitted infections simultaneously, and difficulties to deliver a positive result. French National Authorities for Health propose to screen the population at least once in their lifetime and high-risk people at least once a year. In order to achieve this aim, RHT should be included in the GPs' arsenal for HIV testing. We showed a high acceptability of RHT by GPs. If specific and adapted training is developed, and if solutions to barriers reported by GPs are found, RHT could be implemented in to their routine activity. © The Author(s) 2016.

Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings.

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Shanks, Leslie; Siddiqui, M Ruby; Abebe, Almaz; Piriou, Erwan; Pearce, Neil; Ariti, Cono; Masiga, Johnson; Muluneh, Libsework; Wazome, Joseph; Ritmeijer, Koert; Klarkowski, Derryck

2015-05-14

Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results. Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result. 2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %. This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false

BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

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Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

2014-12-11

The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

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Poongavanam, Vasanthanathan; Kongsted, Jacob

2013-01-01

The increasing resistance to current therapeutic agents for HIV drug regiment remains a major problem for effective acquired immune deficiency syndrome (AIDS) therapy. Many potential inhibitors have today been developed which inhibits key cellular pathways in the HIV cycle. Inhibition of HIV-1...... databases. The methods used here include machine-learning algorithms (e.g. support vector machine, random forest and kappa nearest neighbor), shape similarity (rapid overlay of chemical structures), pharmacophore, molecular interaction fields-based fingerprints for ligands and protein (FLAP) and flexible...... for identifying structurally diverse and selective RNase H inhibitors from large chemical databases. In addition, pharmacophore models suggest that the inter-distance between hydrogen bond acceptors play a key role in inhibition of the RNase H domain through metal chelation....

Lead Screening for HIV-1 Integrase (IN Inhibited by Traditional Chinese Medicine

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Tzu-Chieh Hung

2014-01-01

Full Text Available Human immunodeficiency virus causes the acquired immunodeficiency syndrome (AIDS and becomes a serious world-wide problem because of this disease's rapid propagation and incurability. Integrase strand transfer inhibitors (INSTIs supports HIV have rapid drug resistance for antitreatment. Screening the traditional Chinese medicine (TCM database by simulating molecular docking and molecular dynamics may select molecular compounds to inhibit INSTIs against HIV drug resistance. (S-cathinone and (1S,2S-norpseudoephedrine are selected based on structure and ligand-based drugs are designed and then get higher bioactivity predicted score from SVM than Raltegravir and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions and hydrogen bond variations define the main regions of important amino acids in integrase. In addition to the detection of TCM compound efficacy, we suggest (1S,2S-norpseudoephedrine is better than the others based on the analysis of interaction and the effect on the structural variation.

Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

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Kazem Baesi

2014-09-01

Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

German-austrian recommendations for HIV1-therapy in pregnancy and in HIV1-exposed newborn - update 2008

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Buchholz Bernd

2009-11-01

Full Text Available Abstract German-Austrian recommendations for HIV1-therapy in pregnancy - Update 2008 Bernd Buchholz (University Medical Centre Mannheim, Pediatric Clinic, Matthias Beichert (Mannheim, Gynecology and Obstetrics Practice, Ulrich Marcus (Robert Koch Institute, Berlin, Thomas Grubert, Andrea Gingelmaier (Gynecology Clinic of the Ludwig Maximilians University of Munich, Dr. med. Annette Haberl (HIV-Department, J. W. Goethe-University Hospital, Frankfurt, Dr. med. Brigitte Schmied (Otto-Wagner Spital, Wien. In Germany during the last years about 200-250 HIV1-infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV1-infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV1 was reduced to 1-2%. This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV1-infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV1-infected adults, in 1998, 2001, 2003 and 2005 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO were participating in this conference to update the prevention strategies. A fifth update became necessary in 2008. The updating process was started in January 2008 and was terminated in September 2008. The guidelines provide new recommendations on the indication and the starting point for HIV-therapy in pregnancies without complications, drugs and drug combinations to be

Adolescents' experience of a rapid HIV self-testing device in youth-friendly clinic settings in Cape Town South Africa: a cross-sectional community based usability study.

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Smith, Philip; Wallace, Melissa; Bekker, Linda-Gail

2016-12-23

Introduction : Since HIV testing in South African adolescents and young adults is sub-optimal, the objective of the current study was to investigate the feasibility and acceptability of an HIV rapid self-testing device in adolescents and young people at the Desmond Tutu HIV Foundation Youth Centre and Mobile Clinic. Methods : Self-presenting adolescents and young adults were invited to participate in a study investigating the fidelity, usability and acceptability of the AtomoRapid HIV Rapid self-testing device. Trained healthcare workers trained participants to use the device before the participant conducted the HIV self-test with device usage instructions. The healthcare worker then conducted a questionnaire-based survey to assess outcomes. Results : Of the 224 enrolled participants between 16 and 24 years of age, 155 (69,2%) were female. Overall, fidelity was high; 216 (96,4%) participants correctly completed the test and correctly read and interpreted the HIV test result. There were eight (3,6%) user errors overall; six participants failed to prick their finger even though the lancet fired correctly. There were two user errors where participants failed to use the capillary tube correctly. Participants rated acceptability and usability highly, with debut testers giving significantly higher ratings for both. Younger participants gave significantly higher ratings of acceptability. Conclusions : Adolescents and young adults found HIV self-testing highly acceptable with the AtomoRapid and they used the device accurately. Further research should investigate how, where and when to deploy HIV self-testing as a means to accompany existing strategies in reaching the UNAIDS goal to test 90% of all individuals worldwide.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

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Blonk, Maren I; Colbers, Angela P H; Hidalgo-Tenorio, Carmen; Kabeya, Kabamba; Weizsäcker, Katharina; Haberl, Annette E; Moltó, José; Hawkins, David A; van der Ende, Marchina E; Gingelmaier, Andrea; Taylor, Graham P; Ivanovic, Jelena; Giaquinto, Carlo; Burger, David M

2015-09-01

The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women. An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated. Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9). Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women. NCT00825929. © The Author 2015. Published by Oxford University

DBR1 siRNA inhibition of HIV-1 replication

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Naidu Yathi

2005-10-01

Full Text Available Abstract Background HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1 expression would specifically inhibit HIV-1 replication. Results We designed three short interfering RNA (siRNA molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

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

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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

Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

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Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim; Medina, Candida; da Silva Té, David; Correira, Faustino Gomes; Laursen, Alex Lund; Østergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian

2016-02-01

Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women. © 2015 John Wiley & Sons Ltd.

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India.

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Maity, Susmita; Nandi, Srijita; Biswas, Subrata; Sadhukhan, Salil Kumar; Saha, Malay Kumar

2012-11-26

HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn't vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p bank. For availability of quality commercial diagnostic assays, evaluation of kit may be helpful.

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

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Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

1996-06-01

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Cyclophilin B enhances HIV-1 infection

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DeBoer, Jason; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln, NE (United States)

2016-02-15

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

Cyclophilin B enhances HIV-1 infection

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DeBoer, Jason; Madson, Christian J.; Belshan, Michael

2016-01-01

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

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2011-01-01

Background Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection. Results Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (env) gene as well as a siRNA specific for a downstream target sequence in the subtype D env gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved

Identification of a current hot spot of HIV type 1 transmission in Mongolia by molecular epidemiological analysis.

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Davaalkham, Jagdagsuren; Unenchimeg, Puntsag; Baigalmaa, Chultem; Erdenetuya, Gombo; Nyamkhuu, Dulmaa; Shiino, Teiichiro; Tsuchiya, Kiyoto; Hayashida, Tsunefusa; Gatanaga, Hiroyuki; Oka, Shinichi

2011-10-01

We investigated the current molecular epidemiological status of HIV-1 in Mongolia, a country with very low incidence of HIV-1 though with rapid expansion in recent years. HIV-1 pol (1065 nt) and env (447 nt) genes were sequenced to construct phylogenetic trees. The evolutionary rates, molecular clock phylogenies, and other evolutionary parameters were estimated from heterochronous genomic sequences of HIV-1 subtype B by the Bayesian Markov chain Monte Carlo method. We obtained 41 sera from 56 reported HIV-1-positive cases as of May 2009. The main route of infection was men who have sex with men (MSM). Dominant subtypes were subtype B in 32 cases (78%) followed by subtype CRF02_AG (9.8%). The phylogenetic analysis of the pol gene identified two clusters in subtype B sequences. Cluster 1 consisted of 21 cases including MSM and other routes of infection, and cluster 2 consisted of eight MSM cases. The tree analyses demonstrated very short branch lengths in cluster 1, suggesting a surprisingly active expansion of HIV-1 transmission during a short period with the same ancestor virus. Evolutionary analysis indicated that the outbreak started around the early 2000s. This study identified a current hot spot of HIV-1 transmission and potential seed of the epidemic in Mongolia. Comprehensive preventive measures targeting this group are urgently needed.

HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

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Evans, Edward L; Becker, Jordan T; Fricke, Stephanie L; Patel, Kishan; Sherer, Nathan M

2018-04-01

Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1 NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G 2 /M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif NL4-3 's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G 2 /M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle. IMPORTANCE Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1

Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

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Jairam R Lingappa

Full Text Available The Partners HSV-2/HIV-1 Transmission Study (Partners Study is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2 suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9 with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001.The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission.ClinicalTrials.gov NCT00194519.

Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors.

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Dmitriy Mazurov

2010-02-01

Full Text Available We have developed an efficient method to quantify cell-to-cell infection with single-cycle, replication dependent reporter vectors. This system was used to examine the mechanisms of infection with HTLV-1 and HIV-1 vectors in lymphocyte cell lines. Effector cells transfected with reporter vector, packaging vector, and Env expression plasmid produced virus-like particles that transduced reporter gene activity into cocultured target cells with zero background. Reporter gene expression was detected exclusively in target cells and required an Env-expression plasmid and a viral packaging vector, which provided essential structural and enzymatic proteins for virus replication. Cell-cell fusion did not contribute to infection, as reporter protein was rarely detected in syncytia. Coculture of transfected Jurkat T cells and target Raji/CD4 B cells enhanced HIV-1 infection two fold and HTLV-1 infection ten thousand fold in comparison with cell-free infection of Raji/CD4 cells. Agents that interfere with actin and tubulin polymerization strongly inhibited HTLV-1 and modestly decreased HIV-1 cell-to-cell infection, an indication that cytoskeletal remodeling was more important for HTLV-1 transmission. Time course studies showed that HTLV-1 transmission occurred very rapidly after cell mixing, whereas slower kinetics of HIV-1 coculture infection implies a different mechanism of infectious transmission. HTLV-1 Tax was demonstrated to play an important role in altering cell-cell interactions that enhance virus infection and replication. Interestingly, superantigen-induced synapses between Jurkat cells and Raji/CD4 cells did not enhance infection for either HTLV-1 or HIV-1. In general, the dependence on cell-to-cell infection was determined by the virus, the effector and target cell types, and by the nature of the cell-cell interaction.

Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.

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Ruizhong Shen

Full Text Available Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT. Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

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Vanangamudi, Murugesan; Poongavanam, Vasanthanathan; Namasivayam, Vigneshwaran

2017-01-01

BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising......: The conformation dependent-alignment based (CoMFA and CoMSIA) methods have been proven very successful ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported for structurally distinct NNRTIs including thiazolobenzimidazole, dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine...

HIV rapid testing in a Veterans Affairs hospital ED setting: a 5-year sustainability evaluation.

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Knapp, Herschel; Hagedorn, Hildi; Anaya, Henry D

2014-08-01

Routine HIV testing in primary care settings is now recommended in the United States. The US Department of Veterans Affairs (VA) has increased the number of patients tested for HIV, but overall HIV testing rates in VA remain low. A proven strategy for increasing such testing involves nurse-initiated HIV rapid testing (HIV RT). The purpose of this work was to use a mixed methodology approach to evaluate the 5-year sustainability of an intervention that implemented HIV RT in a VA emergency department setting in a large, urban VA medical center to reduce missed diagnostic and treatment opportunities in this vulnerable patient population. In-person semistructured interviews were conducted with providers and stakeholders. Interview notes were qualitatively coded for emerging themes. Quarterly testing rates were evaluated for a 5-year time span starting from the launch in July 2008. Findings indicate that HIV RT was sustained by the enthusiasm of 2 clinical champions who oversaw the registered nurses responsible for conducting the testing. The departure of the clinical champions was correlated with a substantial drop-off in testing. Findings also indicate potential strategies for improving sustainability including engaging senior leadership in the project, engaging line staff in the implementation planning from the start to increase ownership over the innovation, incorporating information into initial training explaining the importance of the innovation to quality patient care, providing ongoing training to maintain skills, and providing routine progress reports to staff to demonstrate the ongoing impact of their efforts. Published by Elsevier Inc.

Adolescents’ experience of a rapid HIV self-testing device in youth-friendly clinic settings in Cape Town South Africa: a cross-sectional community based usability study

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Smith, Philip; Wallace, Melissa; Bekker, Linda-Gail

2016-01-01

Abstract Introduction: Since HIV testing in South African adolescents and young adults is sub-optimal, the objective of the current study was to investigate the feasibility and acceptability of an HIV rapid self-testing device in adolescents and young people at the Desmond Tutu HIV Foundation Youth Centre and Mobile Clinic. Methods: Self-presenting adolescents and young adults were invited to participate in a study investigating the fidelity, usability and acceptability of the AtomoRapid HIV Rapid self-testing device. Trained healthcare workers trained participants to use the device before the participant conducted the HIV self-test with device usage instructions. The healthcare worker then conducted a questionnaire-based survey to assess outcomes. Results: Of the 224 enrolled participants between 16 and 24 years of age, 155 (69,2%) were female. Overall, fidelity was high; 216 (96,4%) participants correctly completed the test and correctly read and interpreted the HIV test result. There were eight (3,6%) user errors overall; six participants failed to prick their finger even though the lancet fired correctly. There were two user errors where participants failed to use the capillary tube correctly. Participants rated acceptability and usability highly, with debut testers giving significantly higher ratings for both. Younger participants gave significantly higher ratings of acceptability. Conclusions: Adolescents and young adults found HIV self-testing highly acceptable with the AtomoRapid and they used the device accurately. Further research should investigate how, where and when to deploy HIV self-testing as a means to accompany existing strategies in reaching the UNAIDS goal to test 90% of all individuals worldwide. PMID:28406597

78 FR 43055 - Accelerating Improvements in HIV Prevention and Care in the United States Through the HIV Care...

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2013-07-18

... technology, HIV can be detected sooner and more rapidly than ever before. Based on these and other data... that clinicians screen all individuals ages 15 to 65 years for HIV, and the Department of Health and..., including HIV. Starting October 1, 2013, Americans can select the coverage that best suits them through the...

gCUP: rapid GPU-based HIV-1 co-receptor usage prediction for next-generation sequencing.

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Olejnik, Michael; Steuwer, Michel; Gorlatch, Sergei; Heider, Dominik

2014-11-15

Next-generation sequencing (NGS) has a large potential in HIV diagnostics, and genotypic prediction models have been developed and successfully tested in the recent years. However, albeit being highly accurate, these computational models lack computational efficiency to reach their full potential. In this study, we demonstrate the use of graphics processing units (GPUs) in combination with a computational prediction model for HIV tropism. Our new model named gCUP, parallelized and optimized for GPU, is highly accurate and can classify >175 000 sequences per second on an NVIDIA GeForce GTX 460. The computational efficiency of our new model is the next step to enable NGS technologies to reach clinical significance in HIV diagnostics. Moreover, our approach is not limited to HIV tropism prediction, but can also be easily adapted to other settings, e.g. drug resistance prediction. The source code can be downloaded at http://www.heiderlab.de d.heider@wz-straubing.de. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

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Jiang Weimin

2009-05-01

Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1

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Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lee-Kirsch, Min Ae; Lieberman, Judy

2010-01-01

Viral infection triggers innate immune sensors to produce type I interferons (IFN). However, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating nucleic acid sensors is unknown. The cytosolic exonuclease TREX1 suppressed IFN triggered by HIV. In Trex1−/− mouse cells and human CD4+ T cells and macrophages in which TREX1 was inhibited by RNA interference, cytosolic HIV DNA accumulated, and HIV infection induced type I IFN that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate IFN expression via a TBK1, STING and IRF3 dependent pathway. HIV-stimulated IFN production in cells deficient in TREX1 did not involve known nucleic acid sensors. PMID:20871604

Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients

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Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu

2015-01-01

Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4+ T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM increased HIV-1 integration in CD4+ T cells in a dose-dependent manner. As integration can be modulated by several early postentry steps of HIV-1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV-1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4+ T cells and localize to the nucleus-. In summary, our data provide strong evidence that cocaine can increase HIV-1 integration in CD4+ T cells. Therefore, we hypothesize that increased HIV-1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug-abusing HIV-1 patients. PMID:25691383

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

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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.

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

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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

HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

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Irna Sufiawati

Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

Development of an HIV-1 Subtype Panel in China: Isolation and Characterization of 30 HIV-1 Primary Strains Circulating in China.

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Jingwan Han

Full Text Available The complex epidemic and significant diversity of HIV-1 strains in China pose serious challenges for surveillance and diagnostic assays, vaccine development and clinical management. There is a lack of HIV-1 isolates in current canonical HIV-1 subtype panels that can represent HIV-1 diversity in China; an HIV-1 subtype panel for China is urgently needed.Blood samples were collected from HIV-1 infected patients participating in the drug-resistance surveillance program in China. The samples were isolated, cultured and stored as neat culture supernatant. The HIV-1 isolates were fully characterized. The panel was used to compare 2 viral load assays and 2 p24 assays as the examples of how this panel could be used.An HIV-1 subtype panel for China composed of 30 HIV-1 primary strains of four subtypes (B [including Thai-B], CRF01_AE, CRF07_BC and G was established. The samples were isolated and cultured to a high-titer (10(6-10(9 copies/ml/high-volume (40 ml. The HIV-1 isolates were fully characterized by the final viral load, p24 concentration, gag-pol and envC2V3 sequencing, co-receptor prediction, determination of the four amino acids at the tip of the env V3-loop, glycosylation sites in the V3 loop and the drug-resistance mutations. The comparison of two p24 assays and two viral load assays on the isolates illustrated how this panel may be used for the evaluation of diagnostic assay performance. The Pearson value between p24 assays were 0.938. The viral load results showed excellent concordance and agreement for samples of Thai-B, but lower correlations for samples of CRF01_AE.The current panel of 30 HIV-1 isolates served as a basis for the development of a comprehensive panel of fully characterized viral isolates, which could reflect the current dynamic and complex HIV-1 epidemic in China. This panel will be available to support HIV-1 research, assay evaluation, vaccine and drug development.

Stimulation of HIV-1-specific cytolytic T-lymphocytes facilitates elimination of latent viral reservoir after virus reactivation

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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

HIV-1 Reservoir Association with Immune Activation

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Alejandro Vallejo

2015-09-01

Full Text Available In this issue of EBioMedicine, Ruggiero and colleagues describe immune activation biomarkers associated with the size of the HIV reservoir in a carefully designed cross-sectional study. The cohort consists of a homogeneous sample of HIV-1-infected patients with long-term plasma HIV-1 RNA suppression under antiretroviral treatment (ART. It is crucial to explore the potential utility of biomarkers that are easier (less labor intensive, less expensive to measure than integrated HIV DNA load, in order to quickly and accurately quantify cellular reservoirs of HIV.

Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

Science.gov (United States)

Bekele, Yonas; Graham, Rebecka Lantto; Soeria-Atmadja, Sandra; Nasi, Aikaterini; Zazzi, Maurizio; Vicenti, Ilaria; Naver, Lars; Nilsson, Anna; Chiodi, Francesca

2017-01-01

During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of

Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

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Yonas Bekele

2018-01-01

Full Text Available During anti-retroviral therapy (ART HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV and hepatitis B virus (HBV vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory and CD8+ (central memory T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced

Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

Science.gov (United States)

Bekele, Yonas; Graham, Rebecka Lantto; Soeria-Atmadja, Sandra; Nasi, Aikaterini; Zazzi, Maurizio; Vicenti, Ilaria; Naver, Lars; Nilsson, Anna; Chiodi, Francesca

2018-01-01

During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of

The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review

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Saberi P

2012-04-01

Full Text Available Parya Saberi1, Betty J Dong2, Mallory O Johnson1, Ruth M Greenblatt2, Jennifer M Cocohoba21Department of Medicine, 2Department of Clinical Pharmacy, University of California, San Francisco, CA, USAObjective: Due to the rapid proliferation of human immunodeficiency virus (HIV treatment options, there is a need for health care providers with knowledge of antiretroviral therapy intricacies. In a HIV multidisciplinary care team, the HIV pharmacist is well-equipped to provide this expertise. We conducted a systematic review to assess the impact of HIV pharmacists on HIV clinical outcomes.Methods: We searched six electronic databases from January 1, 1980 to June 1, 2011 and included all quantitative studies that examined pharmacist's roles in the clinical care of HIV-positive adults. Primary outcomes were antiretroviral adherence, viral load, and CD4+ cell count and secondary outcomes included health care utilization parameters, antiretroviral modifications, and other descriptive variables.Results: Thirty-two publications were included. Despite methodological limitation, the involvement of HIV pharmacists was associated with statistically significant adherence improvements and positive impact on viral suppression in the majority of studies.Conclusion: This systematic review provides evidence of the beneficial impact of HIV pharmacists on HIV treatment outcomes and offers suggestions for future research.Keywords: pharmacist, HIV/AIDS, clinical, adherence, impact

Curcumin derivatives as HIV-1 protease inhibitors

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Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

1993-12-31

Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

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Chungen Pan

2010-02-01

Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

The dual action of poly(ADP-ribose polymerase -1 (PARP-1 inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

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Slava eRom

2015-08-01

Full Text Available The transcription of HIV-1 (HIV is regulated by complex mechanisms involving various cellular factors and virus-encoded transactivators. Poly(ADP-ribose polymerase 1 (PARP-1 inhibition has emerged recently as a potent anti-inflammatory tool, since PARP-1 is involved in the regulation of some genes through its interaction with various transcription factors. We propose a novel approach to diminish HIV replication via PARP-1 inhibition using human primary monocyte-derived macrophages (MDM as an in vitro model system. PARP-1 inhibitors were able to reduce HIV replication in MDM by 60-80% after 7 days infection. Long Terminal Repeat (LTR acts as a switch in virus replication and can be triggered by several agents such as: Tat, tumor necrosis factor α (TNFα, and phorbol 12-myristate 13-acetate (PMA. Overexpression of Tat in MDM transfected with an LTR reporter plasmid led to a 4.2-fold increase in LTR activation; PARP inhibition resulted in 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85-95%. MDM treated with PARP inhibitors showed 90% reduction in NFκB activity (known to mediate PMA- and TNFα-induced HIV LTR activation. Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These findings suggest that HIV replication in MDM could be suppressed by PARP inhibition via NFκB suppression, diminution of LTR activation and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide a potent approach to treatment of HIV infection.

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

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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

[Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province].

Science.gov (United States)

Deng, Yongyue; Zhang, Chunyang; Yan, Yansheng; Yan, Pingping; Wu, Shouli

2014-06-01

In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology, during 2011-2012. Viral sequences(n = 81) of HIV-1 gag, env, and pol segments were amplified by nested PCR. Subtypes B and four Circulating Recombinant Forms, (CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%) were the two main HIV-1 strains in Fujian province. Compared with previous data, the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.

Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota

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Nunn, Kenetta L.; Wang, Ying-Ying; Harit, Dimple; Humphrys, Michael S.; Ma, Bing; Cone, Richard; Ravel, Jacques

2015-01-01

ABSTRACT Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other sexually transmitted virions from reaching target cells in the vaginal epithelium, thereby preventing or reducing infections. However, the barrier properties of CVM differ from woman to woman, and the causes of these variations are not yet well understood. Using high-resolution particle tracking of fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor total lactic acid levels correlated significantly with virus trapping in unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in CVM with relatively high concentrations of d-lactic acid and a Lactobacillus crispatus-dominant microbiota. In contrast, a substantial fraction of HIV-1 virions diffused rapidly through CVM with low concentrations of d-lactic acid that had a Lactobacillus iners-dominant microbiota or significant amounts of Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. Our results demonstrate that the vaginal microbiota, including specific species of Lactobacillus, can alter the diffusional barrier properties of CVM against HIV and likely other sexually transmitted viruses and that these microbiota-associated changes may account in part for the elevated risks of HIV acquisition linked to bacterial vaginosis or intermediate vaginal microbiota. PMID:26443453

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

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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.

Assessing stakeholder perceptions of the acceptability and feasibility of national scale-up for a dual HIV/syphilis rapid diagnostic test in Malawi.

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Maddox, Brandy L Peterson; Wright, Shauntā S; Namadingo, Hazel; Bowen, Virginia B; Chipungu, Geoffrey A; Kamb, Mary L

2017-12-01

The WHO recommends pregnant women receive both HIV and syphilis testing at their first antenatal care visit, as untreated maternal infections can lead to severe, adverse pregnancy outcomes. One strategy for increasing testing for both HIV and syphilis is the use of point-of-care (rapid) diagnostic tests that are simple, proven effective and inexpensive. In Malawi, pregnant women routinely receive HIV testing, but only 10% are tested for syphilis at their first antenatal care visit. This evaluation explores stakeholder perceptions of a novel, dual HIV/syphilis rapid diagnostic test and potential barriers to national scale-up of the dual test in Malawi. During June and July 2015, we conducted 15 semistructured interviews with 25 healthcare workers, laboratorians, Ministry of Health leaders and partner agency representatives working in prevention of mother-to-child transmission in Malawi. We asked stakeholders about the importance of a dual rapid diagnostic test, concerns using and procuring the dual test and recommendations for national expansion. Stakeholders viewed the test favourably, citing the importance of a dual rapid test in preventing missed opportunities for syphilis diagnosis and treatment, improving infant outcomes and increasing syphilis testing coverage. Primary technical concerns were about the additional procedural steps needed to perform the test, the possibility that testers may not adhere to required waiting times before interpreting results and difficulty reading and interpreting test results. Stakeholders thought national scale-up would require demonstration of cost-savings, uniform coordination, revisions to testing guidelines and algorithms, training of testers and a reliable supply chain. Stakeholders largely support implementation of a dual HIV/syphilis rapid diagnostic test as a feasible alternative to current antenatal testing. Scale-up will require addressing perceived barriers; negotiating changes to existing algorithms and guidelines

[HIV-1 genetic variability in non Spaniard infected children].

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Piñeiro Pérez, R; Mellado Peña, M J; Holguín, A; Cilleruelo, M J; García Hortelano, M; Villota, J; Martín Fontelos, P

2009-01-01

The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, because of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant's response remain undocumented. To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtype C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient's clinical, immunological and virological evolution.

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...

Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

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Pichili Vijaya Bhaskar Reddy

2012-01-01

Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

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

HIV after 40 in Rural South Africa1: A Life Course Approach to HIV Vulnerability among Middle Aged and Older Adults

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Williams, Jill; Angotti, Nicole; Gómez-Olivé, Xavier

2015-01-01

South Africa has the highest number of people living with HIV in the world (over 6 million) as well as a rapidly aging population, with 15% of the population aged 50 and over. High HIV prevalence in rural former apartheid homeland areas suggests substantial aging with HIV and acquisition of HIV at older ages. We develop a life course approach to HIV vulnerability, highlighting the rise and fall of risk and protection as people age, as well as the role of contextual density in shaping HIV vulnerability. Using this approach, we draw on an innovative multi-method data set collected within the Agincourt Health and Demographic Surveillance System in South Africa, combining survey data with 60 nested life history interviews and 9 community focus group interviews. We examine HIV risk and protective factors among adults aged 40–80, as well as how and why these vary among people at older ages. PMID:26364007

Sexually transmitted infections among HIV-1-discordant couples.

Directory of Open Access Journals (Sweden)

Brandon L Guthrie

2009-12-01

Full Text Available More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples.HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI.Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11% females and 30 (7% males. The most prevalent infections were trichomoniasis (5.9% and syphilis (2.6%. Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01, and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01 and those with low education (OR = 3.00; P<0.01. Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01.Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission.ClinicalTrials.gov NCT00194519.

Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

DEFF Research Database (Denmark)

Seng, R; Gustafson, P; Gomes, VF

2002-01-01

BACKGROUND: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42...

Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

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Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

2017-08-25

Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Correlation between HIV-1 genotype and clinical progression in HIV/AIDS patients in Surabaya, Indonesia

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Rachman, B. E.; Khairunisa, S. Q.; Witaningrum, A. M.; Yunifiar, M. Q.; Nasronudin

2018-03-01

Several factors such as host and viral factors can affect the progression of HIV/AIDS. This study aims to identify the correlation viral factors, especially the HIV-1 subtype with HIV/AIDS progression. Inpatient HIV/AIDS during the period March to September 2017 and willing to participate are included in the study. Historical data of disease and treatment was taken by medical record. Blood samples were amplified, sequenced and undergone phylogenetic analysis. Linear regression analysis was used to estimate beta coefficient (β) and 95%CI of HIV/AIDS progression (measured by the CD4 change rate, ΔCD4 cell count/time span in months).This study has 17 samples. The HIV-1 subtype was dominated by CRF01_AE (81.8%) followed by subtype B (18.2%). There was significant correlation between subtype HIV-1 (p = 0.04) and body mass index (p = 0.038) with HIV/AIDS clinical stage. Many factors were assumed to be correlated with increased rate of CD4, but we only subtype HIV-1 had a significant correlation (p = 0.024) with it. From multivariate analysis, we also found that subtype HIV-1 had a significant correlation (β = 0.788, 95%CI: 17.5-38.6, p = 0.004).

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

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Kotaki, Tomohiro; Khairunisa, Siti Qamariyah; Sukartiningrum, Septhia Dwi; Arfijanto, M Vitanata; Utsumi, Takako; Normalina, Irine; Handajani, Retno; Widiyanti, Prihartini; Rusli, Musofa; Rahayu, Retno Pudji; Lusida, Maria Inge; Hayashi, Yoshitake; Nasronudin; Kameoka, Masanori

2013-01-01

Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany

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Meixenberger, Karolin; Pouran Yousef, Kaveh; Somogyi, Sybille; Fiedler, Stefan; Bartmeyer, Barbara; von Kleist, Max; Kücherer, Claudia

2014-01-01

Introduction The aim of our study was to analyze the occurrence and evolution of HIV-1 integrase polymorphisms during the HIV-1 epidemic in Germany prior to the introduction of the first integrase inhibitor raltegravir in 2007. Materials and Methods Plasma samples from drug-naïve HIV-1 infected individuals newly diagnosed between 1986 and 2006 were used to determine PCR-based population sequences of the HIV-1 integrase (amino acids 1–278). The HIV-1 subtype was determined using the REGA HIV-1 subtyping tool. We calculated the frequency of amino acids at each position of the HIV-1 integrase in 337 subtype B strains for the time periods 1986–1989, 1991–1994, 1995–1998, 1999–2002, and 2003–2006. Positions were defined as polymorphic if amino acid variation was >1% in any period. Logistic regression was used to identify trends in amino acid variation over time. Resistance-associated mutations were identified according to the IAS 2013 list and the HIVdb, ANRS and GRADE algorithms. Results Overall, 56.8% (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these positions exhibited a significant trend in amino acid variation over time. Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N-terminal zinc finger domain of the HIV-1 integrase. Motifs and residues essential for HIV-1 integrase activity were little polymorphic, but within the minimal non-specific DNA binding region I220-D270 up to 18.1% amino acid variation was noticed, including four positions with significant amino acid variation over time (S230, D232, D256, A265). No major resistance mutations were identified, and minor resistance mutations were rarely observed without trend over time. E157Q considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance-associated polymorphism with an overall prevalence of 2.4%. Conclusions Detailed knowledge of the evolutionary variation of HIV-1 integrase polymorphisms is important to understand

Cyclophilin B enhances HIV-1 infection.

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DeBoer, Jason; Madson, Christian J; Belshan, Michael

2016-02-01

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

The global transmission network of HIV-1.

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Wertheim, Joel O; Leigh Brown, Andrew J; Hepler, N Lance; Mehta, Sanjay R; Richman, Douglas D; Smith, Davey M; Kosakovsky Pond, Sergei L

2014-01-15

Human immunodeficiency virus type 1 (HIV-1) is pandemic, but its contemporary global transmission network has not been characterized. A better understanding of the properties and dynamics of this network is essential for surveillance, prevention, and eventual eradication of HIV. Here, we apply a simple and computationally efficient network-based approach to all publicly available HIV polymerase sequences in the global database, revealing a contemporary picture of the spread of HIV-1 within and between countries. This approach automatically recovered well-characterized transmission clusters and extended other clusters thought to be contained within a single country across international borders. In addition, previously undescribed transmission clusters were discovered. Together, these clusters represent all known modes of HIV transmission. The extent of international linkage revealed by our comprehensive approach demonstrates the need to consider the global diversity of HIV, even when describing local epidemics. Finally, the speed of this method allows for near-real-time surveillance of the pandemic's progression.

Cost-effectiveness of HIV and syphilis antenatal screening: a modelling study.

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Bristow, Claire C; Larson, Elysia; Anderson, Laura J; Klausner, Jeffrey D

2016-08-01

The WHO called for the elimination of maternal-to-child transmission (MTCT) of HIV and syphilis, a harmonised approach for the improvement of health outcomes for mothers and children. Testing early in pregnancy, treating seropositive pregnant women and preventing syphilis reinfection can prevent MTCT of HIV and syphilis. We assessed the health and economic outcomes of a dual testing strategy in a simulated cohort of 100 000 antenatal care patients in Malawi. We compared four screening algorithms: (1) HIV rapid test only, (2) dual HIV and syphilis rapid tests, (3) single rapid tests for HIV and syphilis and (4) HIV rapid and syphilis laboratory tests. We calculated the expected number of adverse pregnancy outcomes, the expected costs and the expected newborn disability-adjusted life years (DALYs) for each screening algorithm. The estimated costs and DALYs for each screening algorithm were assessed from a societal perspective using Markov progression models. Additionally, we conducted a Monte Carlo multiway sensitivity analysis, allowing for ranges of inputs. Our cohort decision model predicted the lowest number of adverse pregnancy outcomes in the dual HIV and syphilis rapid test strategy. Additionally, from the societal perspective, the costs of prevention and care using a dual HIV and syphilis rapid testing strategy was both the least costly ($226.92 per pregnancy) and resulted in the fewest DALYs (116 639) per 100 000 pregnancies. In the Monte Carlo simulation the dual HIV and syphilis algorithm was always cost saving and almost always reduced DALYs compared with HIV testing alone. The results of the cost-effectiveness analysis showed that a dual HIV and syphilis test was cost saving compared with all other screening strategies. Updating existing prevention of mother-to-child HIV transmission programmes in Malawi and similar countries to include dual rapid testing for HIV and syphilis is likely to be advantageous. Published by the BMJ Publishing Group

Situation of Linkage between Sexual and Reproductive Health and HIV-Related Policies in Islamic Republic of Iran – A Rapid Assessment in 2011–2

Directory of Open Access Journals (Sweden)

Ghobad Moradi

2015-03-01

Full Text Available The number of sexual transmission of HIV is increasing globally. Sexual and Reproductive Health (SRH issues and HIV/AIDS related problems are rooted in common grounds such as poverty, gender inequality, and social exclusion. As a result, international health organizations have suggested the integration of SRH services with HIV/AIDS services as a strategy to control HIV and to improve people’s access to SRH services. The aim of this study was to evaluate the relationship between reproductive health and HIV/AIDS services at policy-making level in Islamic Republic of Iran (IRI. This study was conducted in 2011–2 and was a rapid assessment based on guidelines provided by the World Health Organization (WHO, United Nations Programme on HIV/AIDS (UNAIDS, Family Health International Association, and some other international organizations. In this rapid assessment we used different methods such as a review of literature and documents, visiting and interviewing professionals and experts in family health and HIV/AIDS programs, and experts working in some NonGovernmental Organizations (NGOs. Overall, based on the results obtained in this study, in most cases there was not much linkage between HIV/AIDS policies and SRH policies in Iran. Since integration of HIV/AIDS services and SRH services is recommended as a model and an appropriate response to HIV epidemics worldwide, likewise to control the HIV/AIDS epidemic in Iran it is required to integrate HIV/AIDS and SRH services at all levels, particularly at the policy-making level.

HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

Science.gov (United States)

Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

2018-05-18

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

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.

Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

Science.gov (United States)

Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

2004-12-01

HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

Evaluation of three commercial rapid tests for detecting antibodies to human immunodeficiency virus.

Science.gov (United States)

Ng, K P; Saw, T L; Baki, A; Kamarudin, R

2003-08-01

Determine HIV-1/2, Chembio HIV-1/2 STAT-PAK and PenTest are simple/rapid tests for the detection of antibodies to HIV-1 and HIV-2 in human whole blood, serum and plasma samples. The assay is one step and the result is read visually within 15 minutes. Using 92 known HIV-1 reactive sera and 108 known HIV-1 negative sera, the 3 HIV tests correctly identified all the known HIV-1 reactive and negative samples. The results indicated that Determine HIV-1/2, Chembio HIV-1/2 STAT-PAK and PenTest HIV are as sensitive and specific (100% concordance) as Microparticle Enzyme Immunoassay. The data indicated that these 3 HIV tests are effective testing systems for diagnosis of HIV infection in a situation when the conventional Enzyme Immunoassay is not suitable.

Sieve analysis in HIV-1 vaccine efficacy trials.

Science.gov (United States)

Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

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Sachin Gupta

Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation

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Liu, Xiaoqing; Xiu, Zhilong; Hao, Ce

2009-05-01

Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the major targets of anti-AIDS drug discovery. The circulating recombinant form 01 A/E (CRF01_AE, abbreviated AE) subtype is one of the most common HIV-1 subtypes, which is infecting more humans and is expanding rapidly throughout the world. It is, therefore, necessary to develop inhibitors against subtype AE HIV-1 PR. In this work, we have performed computer simulation of subtype AE HIV-1 PR with the drugs lopinavir (LPV) and nelfinavir (NFV), and examined the mechanism of resistance of the V82F mutation of this protease against LPV both structurally and energetically. The V82F mutation at the active site results in a conformational change of 79's loop region and displacement of LPV from its proper binding site, and these changes lead to rotation of the side-chains of residues D25 and I50'. Consequently, the conformation of the binding cavity is deformed asymmetrically and some interactions between PR and LPV are destroyed. Additionally, by comparing the interactive mechanisms of LPV and NFV with HIV-1 PR we discovered that the presence of a dodecahydroisoquinoline ring at the P1' subsite, a [2-(2,6-dimethylphenoxy)acetyl]amino group at the P2' subsite, and an N2 atom at the P2 subsite could improve the binding affinity of the drug with AE HIV-1 PR. These findings are helpful for promising drug design.

Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

Science.gov (United States)

Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

2016-03-01

The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

African Journals Online (AJOL)

out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

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Michael S Harper

Full Text Available HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8 and weak (IFNα1 subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

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Tomohiro Kotaki

Full Text Available Human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs, we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs.The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1 and the prevalence of other blood-borne viruses, hepatitis B virus (HBV, hepatitis C virus (HCV and GB virus C (GBV-C, were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients.The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%. In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity.

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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.

Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.

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Morris, Sheldon R; Woods, Steven Paul; Deutsch, Reena; Little, Susan J; Wagner, Gabriel; Morgan, Erin E; Heaton, Robert K; Letendre, Scott L; Grant, Igor; Smith, Davey M

2013-10-01

HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.

HIV/HTLV-1 co-infection

African Journals Online (AJOL)

result of a lymphoproliferative disorder. In the context of HIV co-infection, lympho- cytosis has been described during early sero- conversion associated with CMV, as well as in HIV/HTLV-1 co-infection where CD4+ lymphocytosis can be caused by both a reactive or clonal expansion. Consequently, patients with untreated ...

Molecular Epidemiology of HIV-1 Infection among Men who Have Sex with Men in Taiwan in 2012.

Science.gov (United States)

Huang, Szu-Wei; Wang, Sheng-Fan; Cowó, Ángel E; Chen, Marcelo; Lin, Yu-Ting; Hung, Chun-Po; Chen, Yi-Hsien; Yang, Jyh-Yuan; Tang, Hung-Jen; Chen, Yi-Ming Arthur

2015-01-01

The number of men who have sex with men (MSM) infected with HIV-1 in Taiwan has increased rapidly in the past few years. The goal of this study was to conduct a molecular epidemiological study of HIV-1 infection among MSM in Taiwan to identify risk factors for intervention. Voluntary counseling program and anonymous testing were provided to patrons at 1 gay bar, 7 night clubs and 3 gay saunas in Taipei and New Taipei Cities in 2012. HIV-1 subtypes were determined using gag subtype-specific PCR and phylogenetic analysis by env sequences. Recent HIV-1 infection was determined using LAg-Avidity EIA. In-depth interviews and questionnaires were used to identify risk factors. The prevalence and incidence of HIV-1 among MSM in Taiwan were 4.38% (53/1,208) and 3.29 per 100 person-years, respectively. Of 49 cases genotyped, 48 (97.9%) were infected with subtype B and 1 with CRF01_AE (2%). Phylogenetic analysis of 46 HIV-1 strains showed that 25 (54.4%) subtype B strains formed 9 clusters with each other or with other local strains. The CRF01_AE case clustered with a reference strain from a Thai blood donor with bootstrap value of 99. Multivariate logistic regression analysis showed that risk factors associated with HIV-1 infection included use of oil-based solution as lubricant (vs. saliva or water-based lubricants, OR= 4.23; p watch?v=BinExvvOTMM&feature=iv&src_vid=BW81-PfmY3E&annotation_id=annotation_2436493705) to correct such misconception in its AIDS prevention campaign.

HIV-1 infection: the role of the gastrointestinal tract.

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Cavarelli, Mariangela; Scarlatti, Gabriella

2014-06-01

The intestinal mucosa has an important role as portal of entry during mother-to-child transmission of HIV-1 and during sexual transmission. Tissue morphology and integrity, as well as distribution of relevant cell types within the mucosa, spanning from the oropharynx to the rectum, can greatly influence viral infection, replication, presentation, and persistence. The relative contribution to transmission by cell-associated or cell-free virus is still not defined for the different routes of transmission. Although the main target cells for HIV-1 replication are the CD4+ T lymphocytes, which are rapidly depleted both in the periphery and in the mucosal tissues, dendritic cells, Langerhans' cells, and macrophages are players in each of these processes. The predominant cells involved may differ according to the tract of the gut and the route of transmission. The microenvironment of the intestinal mucosa, including mucus, antibodies, or chemo-cytokines, can as well influence infection and replication of the virus: their role is still under investigation. The understanding of these processes may help in developing efficient prevention strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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 ...

Correlates of HIV-1 genital shedding in Tanzanian women.

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Clare Tanton

2011-03-01

Full Text Available Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania.Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load.Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load.RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

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Ireen E Kiwelu

Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

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Anne Mette Fisker Hag

Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

Science.gov (United States)

Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

2014-10-03

Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. Copyright © 2014, American Association for the Advancement of Science.

HIV-1 protease inhibitory substances from Cassia garrettiana

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Jindaporn Puripattanvong

2007-01-01

Full Text Available Cassia garrettiana Craib, a Thai medicinal plant locally known as Samae-sarn, was investigated for its active constituents against HIV-1 protease (HIV-1 PR. Bioassay-guided fractionation of the heart woodof this plant led to the isolation of a stilbene derivative (1, piceatannol and an anthraquinone derivative (2, chrysophanol. Piceatannol exhibited appreciable inhibitory effect against HIV-1 PR with an IC50 value of25.4 μg/ml, whereas that of chrysophanol was 73.5 μg/ml. In addition, other two stilbenoids together with three anthraquinone derivatives were also investigated for their anti-HIV-1 PR activities. The resultindicated that resveratrol possessed anti-HIV-1 PR activity with an IC50 value of 85.0 μg/ml, whereas other stilbenoid (oxyresveratrol and anthraquinone derivatives (emodin, aloe-emodin, rhein were inactive (IC50 > 100 μg/ml.

The Epidemiology of HIV-1 Transmitted Drug Resistance

NARCIS (Netherlands)

D. Frentz (Dineke)

2012-01-01

textabstractThe human immunodeficiency virus (HIV) was first discovered in 1983. In 2009, it was estimated that 33.3 (31.4 -35.3) million individuals are infected with HIV worldwide. In that year 1.8 (1.6-2.1) million people died from HIV. Although the virus continues to spread, the number of new

Increased Risk of Female HIV-1 Acquisition Throughout Pregnancy and Postpartum: A Prospective Per-coital Act Analysis Among Women with HIV-1 Infected Partners.

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Thomson, Kerry A; Hughes, James; Baeten, Jared M; John-Stewart, Grace; Celum, Connie; Cohen, Craig R; Ngure, Kenneth; Kiarie, James; Mugo, Nelly; Heffron, Renee

2018-03-05

Understanding the absolute and relative risk of HIV-1 acquisition during pregnancy and postpartum can inform HIV-1 prevention strategies for women. We used a complementary log-log model and data from 2,751 HIV-1 serodiscordant couples to compare the probability of women's HIV-1 acquisition risk per sex act during early pregnancy, late pregnancy, postpartum, and non-pregnant periods. At total of 686 pregnancies were identified and 82 incident HIV-1 infections occurred. After adjustment for condom use, age, PrEP use, and HIV-1 viral load, the per act probability of HIV-1 acquisition was higher in late pregnancy (aRR 2.82, p=0.01) and postpartum (aRR 3.97, p=0.01) compared to non-pregnant periods. The HIV-1 acquisition probability per condomless sex act for a 25 year old woman not taking PrEP with an HIV-1 infected male partner with viral load of 10,000 copies/ml was 0.0011 (95% CI: 0.005, 0.0019), 0.0022 (95% CI: 0.0004, 0.0093), 0.0030 (95% CI: 0.0007, 0.0108), and 0.0042 (95% CI: 0.0007, 0.0177) in the non-pregnant, early pregnant, late pregnant, and postpartum periods, respectively. The HIV-1 acquisition probability per condomless sex act steadily increased through pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and postpartum increase female HIV-1 susceptibility.

Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation

DEFF Research Database (Denmark)

Yusim, K.; Kesmir, Can; Gaschen, B.

2002-01-01

The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequenc...

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.

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Hui Li

2010-05-01

Full Text Available Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM and found that a high proportion (10 of 28; 36% had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38% versus 34 of 175 subjects (19%; Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml. All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

Science.gov (United States)

Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

2014-07-01

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.