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1.  Quantiferon-TB Gold: Performance for Ruling out Active Tuberculosis in HIV-Infected Adults with High CD4 Count in Côte d'Ivoire, West Africa 
PLoS ONE  2014;9(10):e107245.
To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT).
Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml.
Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion.
A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.
Trial Registration NCT00495651.
PMCID: PMC4199568  PMID: 25330161
2.  CD4 eligibility thresholds: an analysis of the time to antiretroviral treatment in West African HIV-1 seroconverters 
AIDS (London, England)  2011;25(6):819-823.
WHO recommends initiating combination antiretroviral treatment (ART) at the minimal threshold of 350 CD4 cells/mm3. In sub-Saharan Africa, the time for a recently infected patient to reach this threshold is unclear.
We estimated the probability of reaching different CD4 thresholds over time in the ANRS 1220 cohort of HIV-1 seroconverters in Côte d’Ivoire. CD4 slopes were estimated using a mixed linear model. Probabilities of crossing the 350 and 500 CD4 cells/mm3 thresholds were estimated by the Kaplan-Meier method.
Between 1997 and 2009, 304 recent seroconverters have been enrolled in the Primo-CI cohort (62% men, median baseline age 29 years, median time since the estimated date of seroconversion 9 months). The probability of having a first CD4 count below 500/mm3 was 0.57, 0.72, 0.79 and 0.84 at study entry, 2, 4 and 6 years, respectively. For a first CD4 count below 350/mm3, these figures were 0.29, 0.40, 0.55 and 0.67. The time for 75% of patients to reach the threshold was 3.0 years for 500 CD4/mm3 and 7.0 years for 350 CD4/mm3.
Almost one third of recent seroconverters had a CD4 count below the current ART eligibility threshold at first contact, about 6% more crossed it each subsequent year, and 25% remained above this threshold after 7 years. If the threshold was raised to 500 cells/mm3, 57% of recent seroconverters would immediately be eligible, while 14% would remain above the threshold at 7 years. These results should help modelers and treatment providers anticipate the need in antiretroviral drugs.
PMCID: PMC3921664  PMID: 21412060
3.  Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm▿ † 
Journal of Virology  2009;83(14):7337-7348.
The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC50) neutralization titers of ≥100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC50 titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.
PMCID: PMC2704778  PMID: 19439467
4.  Anthropometric and immunological success of antiretroviral therapy and prediction of virological success in west African adults 
The 6-month assessment of the response to antiretroviral therapy (ART) is a critical step. In sub-Saharan Africa, few people have access to plasma viral load (VL) measurement. We assessed the gain or loss in BMI (ΔBMI), alone or in combination with the gain or loss in CD4 (ΔCD4), as a tool for predicting the response to ART at 6 months.
In a cohort of 622 adults in Abidjan, we calculated the sensitivity, specificity and predictive values of ΔBMI and ΔCD4 for treatment success, with VL undetectability (<300 copies/ml) as gold standard.
After 6 months of ART, the median ΔBMI was +1.0 kg/m2 (interquartile range [IQR] +0.0; +2.1), the median ΔCD4 was +148/mm3 (IQR +54; +230) and 84% of patients reached VL undetectability. The distribution of ΔBMI was similar among patients who reached VL undetectability and those who did not (median +1.06 vs. +0.99 kg/m2, p = 0.51). With increasing ΔBMI, the specificity of ΔBMI for treatment success increased but its sensitivity decreased and its positive predictive value remained stable around 85%. All results remained similar when combining ΔBMI with ΔCD4 and when stratifying by groups of baseline BMI or CD4.
In settings where VL measurement is not available, a high BMI gain should not be interpreted as reflecting virological success, even when combined with a high CD4 gain. In our population, most patients with detectable VL were probably sufficiently adherent to reach significant BMI and CD4 gain but insufficiently adherent to reach VL suppression.
PMCID: PMC2486368  PMID: 18568272
sub-Saharan Africa; HAART; body mass index; CD4 count; virological success; adults; predictive value
5.  Immune status and uptake of antiretroviral interventions to prevent mother-to-child transmission of HIV-1 in Africa 
The aim of this study was to describe the distribution of CD4+ T cell count (CD4) of HIV-1 infected pregnant women diagnosed during prenatal counseling and testing (VCT), in Abidjan, Côte d’Ivoire, and to assess whether HIV-related immunodeficiency influenced or not the acceptance of an antiretroviral package to prevent mother-to-child transmission. Between April and June 2002, CD4 count was systematically performed in all women diagnosed as HIV-infected (n=221) in five antenatal clinics carrying out VCT. Their median CD4 was 408 cells/mm3 and 14% were < 200 CD4. The overall uptake of the intervention (31.9%) was independent of the immune status.
PMCID: PMC2475580  PMID: 15167296
Adult; Anti-HIV Agents; administration & dosage; CD4 Lymphocyte Count; Cote d'Ivoire; Disease Transmission; Vertical; Female; HIV Infections; complications; drug therapy; immunology; prevention & control; transmission; HIV-1; Humans; Infant; Newborn; Nevirapine; administration & dosage; Patient Acceptance of Health Care; Pregnancy; Pregnancy Complications; Infectious; drug therapy; immunology; Zidovudine; administration & dosage
6.  Field Evaluation of a Rapid Human Immunodeficiency Virus (HIV) Serial Serologic Testing Algorithm for Diagnosis and Differentiation of HIV Type 1 (HIV-1), HIV-2, and Dual HIV-1-HIV-2 Infections in West African Pregnant Women 
Journal of Clinical Microbiology  2004;42(9):4147-4153.
We evaluated a two-rapid-test serial algorithm using the Determine and Genie II rapid assays, performed on-site in four peripheral laboratories during the French Agence Nationale de Recherches sur le SIDA (ANRS) 1201/1202 Ditrame Plus cohort developed for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection in Côte d'Ivoire. A total of 1,039 specimens were retested by two commercial enzyme-linked immunosorbent assays (ELISAs). The following specimens were tested: 315 specimens found on-site to be infected with HIV type 1 (HIV-1), 8 specimens found on-site to be infected with HIV-2, 71 specimens found on-site to be infected with both HIV-1 and HIV-2, 40 specimens found on-site to have indeterminate results for HIV infection, and 605 specimens taken during a quality assurance program. For HIV discrimination, 99 positive serum samples (20 with HIV-1, 8 with HIV-2, and 71 with HIV-1 and HIV-2 on the basis of our rapid test algorithm) were retested by the Peptilav test, Western blot (WB) assays, and homemade monospecific ELISAs. Real-time DNA PCRs for the detection of HIV-1 and HIV-2 were performed with peripheral blood mononuclear cells from 35 women diagnosed on-site with HIV-1 and HIV-2 infections. Compared to the results of the ELISAs, the sensitivities of the Determine and Genie II assays were 100% (95% lower limit [95% LL], 99.1%) and 99.5% (95% confidence interval [95% CI], 98.2 to 99.9%), respectively. The specificities were 98.4% (95% CI, 96.9 to 99.3%) and 100% (95% LL, 99.3%), respectively. All serological assays gave concordant results for infections with single types. By contrast, for samples found to be infected with dual HIV types by the Genie II assay, dual reactivity was detected for only 37 samples (52.1%) by WB assays, 34 samples (47.9%) by the Peptilav assay, and 23 samples (32.4%) by the monospecific ELISAs. For specimens with dual reactivity by the Genie II assay, the rates of concordance between the real-time PCR assays and the serological assays were 25.7% for the Genie II assay, 82.9% for the Peptilav assay, 74.3% for WB assays, and 80% for the homemade ELISAs. Our algorithm provided high degrees of sensitivity and specificity comparable to those of ELISAs. Even if they are rare, women identified by the Genie II assay as being infected with HIV-1 and HIV-2 mostly appeared to be infected only with HIV-2.
PMCID: PMC516348  PMID: 15365003

Results 1-6 (6)