HIV-specific T helper responses and frequency of exposure among HIV-exposed seronegative female sex workers in Abidjan, Côte d'Ivoire

BACKGROUND: The characteristics of human immunodeficiency virus (HIV) exposure that determine the induction of HIV-specific T cells and, in particular, T helper cells are not well understood. METHODS: HIV-1 Gag- and Env-specific T helper cells were analyzed by use of an interferon (IFN)- gamma enzyme-linked immunosorbent spot (ELISPOT) assay and by use of IFN- gamma secretion flow cytometry. Responses among HIV-exposed seronegative (ESN) female sex workers (FSWs) were compared with responses among HIV-seropositive FSWs and HIV-seronegative female blood donors from Abidjan, Cote d'Ivoire. RESULTS: Low-level ELISPOT responses were detected in 8 (20%) of 40 ESN FSWs. All of 25 HIV-seropositive FSWs had high-level ELISPOT responses. HIV-specific CD4+ T cells and, occasionally, CD8+ T cells were detected by secretion flow cytometry in 3 (38%) of 8 ESN FSWs and in 4 (80%) of 5 HIV-seropositive FSWs. ESN FSWs with detectable HIV-specific T helper responses had more clients on the previous working day (P=.02) and more exposures to HIV per month (P=.02) and tended to have a lower total duration of commercial sex work. CONCLUSIONS: These findings demonstrate that the presence of HIV-specific T helper cells in ESN FSWs is associated with the frequency, rather than the duration, of exposure to HIV. The data may have important implications for the evaluation of HIV vaccine efficacy

Quantification of HIV-1 p24 by a highly improved ELISA: An alternative to HIV-1 RNA based treatment monitoring in patients from Abidjan, Côte d'Ivoire.

BACKGROUND: Quantification of HIV-1 RNA remains difficult to implement in Africa. Simple and inexpensive tests for antiretroviral treatment (ART) monitoring are needed. OBJECTIVE: To evaluate an HIV-1 p24 ELISA, which combines efficient virus disruption, heat-denaturation and signal amplification, in a West African setting. STUDY DESIGN: Eighty-six HIV-1 infected patients from Abidjan, Côte d'Ivoire, were tested for p24, HIV-1 RNA, and CD4+ count at baseline, and twice within 8 months after ART initiation. RESULTS: All patients responded to ART with a minimal HIV-1 RNA drop of 0.5log(10) at first follow-up. Forty-one (47.7%) then rebounded >0.5log(10) or persisted above 1000copies/mL by week 24. The predicted baseline concentration of p24 corresponding to 100,000copies/mL of HIV-1 RNA, above which ART is recommended, was 4546fg/mL (95% confidence interval 3148-6566). A prediction model of virologic failure, occurring after an initial response to ART, correctly classified 84% of patients using baseline p24, p24 change on therapy, and achievement of undetectable p24 as explanatory variables. The model and further bootstrap evaluation suggested a good ability to discriminate between sustained or failing virologic response to ART. CONCLUSION: HIV-1 p24 and RNA based-ART monitoring in a low-resource country dominated by HIV-1 CRF02 AG appeared comparable

Differences in HIV-2 plasma viral load and immune activation in HIV-1 and HIV-2 dually infected persons and those infected with HIV-2 only in Abidjan, Côte d'Ivoire

Not the final published versionOBJECTIVE: To determine whether blood plasma levels of HIV-2 RNA viral loads and immune activation markers differ between persons infected with HIV-2 only and those dually infected with HIV-1 and HIV-2. METHODS: Between September 1996 and February 2000, we collected, analyzed and compared levels of HIV-2 RNA in plasma and immune activation markers among 52 persons infected with HIV-2 alone and 75 with confirmed dual infection. We also compared viral load and immune activation in patients who were infected with HIV-1 only and those who were dually infected. RESULTS: When we conducted a CD4 T-cell count-stratified multivariate analysis of HIV-2 viral load, controlling for difference in CD4 T-cell counts, age and sex: at 500 x 10/l, HIV-2 viral load was 0.9 log10 copies/ml higher in dually infected patients (P < 0.0001). Dually infected persons with undetectable HIV-2 viral loads had significantly higher median levels of CD8 T cells expressing CD38 (P < 0.001) and HLA-DR (P = 0.01) than HIV-2 only infected patients. CONCLUSION: These results suggest that in dual infection, the level of HIV-2 replication depends on the immune status of the patients, with HIV-1 out-replicating HIV-2 as disease progress

Changes in level of immune activation and reconstitution among HIV-1-infected Africans receiving antiretroviral therapy

Not the final published versionOBJECTIVE: To describe changes in immune activation and reconstitution markers among HIV-1-infected patients receiving antiretroviral therapy (ART) in Abidjan, Côte d'Ivoire. METHODS: Between November 1998 and February 2001, we analyzed changes in immune activation and reconstitution markers among 52 patients. Good virologic responders (n = 26) were defined as those who had suppressed and maintained plasma viral load (VL) below the detection limit of the assay for at least 12 months. Poor virologic responders (n = 26) were defined as those with a detectable VL at 6 and 12 months after beginning ART. RESULTS: Of the 26 good virologic responders, 20 (77%) were on highly active antiretroviral therapy (HAART) compared with one (4%) of the poor responders. Among the 26 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Median levels of HLA-DR+CD8+ T cells also decreased from baseline at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ T cells increased steadily during the 6 and 12 months of therapy and reached levels observed among HIV-negative blood donors (P = 0.07). Among the 26 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 12 months of therapy (P = 0.006), but were higher than levels in blood donors (P = 0.005). Levels of HLA-DR+CD8+ T cells decreased significantly at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ decreased over time. CONCLUSION: Our results suggest that HAART can be successfully used in African populations with elevated baseline immune activation markers

Evaluating the BED capture enzyme immunoassay to estimate HIV incidence among adults in three countries in sub-Saharan Africa

Serological assays for estimating HIV-1 incidence are prone to misclassification, limiting the accuracy of the incidence estimate. Adjustment factors have been developed and recommended for estimating assay-based HIV-1 incidence in cross-sectional settings. We evaluated the performance of the recommended adjustment factors for estimating incidence in national HIV surveys in three countries in sub-Saharan Africa. The BED-capture enzyme immunoassay was applied to stored blood specimens from (1) pregnant women aged 15-49 years attending antenatal clinics in Cote d'Ivoire (1998-2004), (2) adults aged 15-49 years participating in a demographic health survey in Kenya (2003), and (3) adults aged 15-49 years participating in a national household serosurvey in South Africa (2005). Assay-derived incidence estimates were corrected for misclassification using recommended adjustment factors and, where possible, were compared to mathematically modeled incidence in the same populations. Trends in HIV prevalence were compared to trends in assay-derived incidence to assess plausibility in the assay-derived trends.

Evaluating the BED capture enzyme immunoassay to estimate HIV incidence among adults in three countries in sub-Saharan Africa

Serological assays for estimating HIV-1 incidence are prone to misclassification, limiting the accuracy of the incidence estimate. Adjustment factors have been developed and recommended for estimating assay-based HIV-1 incidence in cross-sectional settings. We evaluated the performance of the recommended adjustment factors for estimating incidence in national HIV surveys in three countries in sub-Saharan Africa. The BED-capture enzyme immunoassay was applied to stored blood specimens from (1) pregnant women aged 15-49 years attending antenatal clinics in Côte d'Ivoire (1998-2004), (2) adults aged 15-49 years participating in a demographic health survey in Kenya (2003), and (3) adults aged 15-49 years participating in a national household serosurvey in South Africa (2005). Assay-derived incidence estimates were corrected for misclassification using recommended adjustment factors and, where possible, were compared to mathematically modeled incidence in the same populations. Trends in HIV prevalence were compared to trends in assay-derived incidence to assess plausibility in the assay-derived trends. Unadjusted incidence was 3.8% [95% confidence interval (CI) 3.3-4.5] in Côte d'Ivoire, 3.5% (2.7-4.3) in Kenya, and 4.4% (CI 2.3-6.5]) in South Africa. Adjusted incidence was 2.9% (CI 2.1-3.7) in Côte d'Ivoire, 2.6% (CI 2.0-3.2) in Kenya, and 2.4% (CI 1.7-3.1) in South Africa. After adjustment, peak incidence shifted from older to younger age groups in Côte d'Ivoire and South Africa. Modeled HIV incidence was 1.0% (CI 1.02-1.08) in Kenya and 2.0% (CI 1.7-2.4) in South Africa. After applying the recommended adjustments factors, adjusted assay-derived estimates remained implausibly high in two of three populations evaluated. For more accurate measures of assay-derived population incidence, adjustment factors must be locally derived and validated. Until improved assays are available, caution should be applied in the use and interpretation of data from incidence assays. Copyright 2010, Mary Ann Liebert, Inc.Articl

An International Collaboration To Standardize HIV-2 Viral Load Assays: Results from the 2009 ACHIEV2E Quality Control Study▿

Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHIEV2E study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log10 copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log10 copies/ml and 3.7 log10 copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed