Molecular confirmation of HIV-1 and HIV-2 coinfections among initially serologically dually-reactive samples from patients living in West Africa.

OBJECTIVES: This study aimed to confirm the co-infection with HIV-1 and HIV-2, among West African patients using in-house HIV type/group enzyme-immuno assays and molecular diagnosis. DESIGN: A cross-sectional survey was conducted from April 2016 to October 2017 in the biggest HIV clinics of Côte d'Ivoire and Burkina Faso. METHOD: A first serological confirmation was done in the referral laboratory using an in-house, indirect immuno-enzymatic essay allowing the qualitative detection of both HIV-1 and HIV-2 antibodies. In order to separately detect anti-HIV-1 and anti-HIV-2 antibodies, a type/group specific enzyme-immuno assay (HIV-GSEIA) was used. To confirm the co-infections, HIV-1 and HIV-2 DNA-qualitative PCR assays were performed. RESULTS: A total of 91 patients were enrolled in the study and provided blood sample for HIV type confirmatory testing including 13 (14.3%) HIV-2 mono-reactive and 78 (85.7%) HIV-1/HIV-2 dually-reactive based on the HIV testing National Algorithms. The first serological ELISA confirmatory test performed showed that 80 (78.9%) of the 91 participants were dually-reactive. The HIV-GSEIA performed on these 80 serum samples retrieve one 61 HIV-1/HIV-2 dually-reactive samples. HIV-1 and HIV-2 DNA PCR were performed on 54 of the 61 HIV-1/HIV-2 dually-reactive samples and 46 out of 61 (75.4%) samples were found HIV-1/HIV-2 coinfected. CONCLUSION: The contribution of type/group specific enzyme-immuno assay to accurately identify HIV-1/HIV-2 coinfections remain suboptimal, emphasizing the need for molecular diagnosis platforms in West Africa, to avail HIV DNA PCR test for the confirmation of HIV-1/HIV-2 co-infections.

Validation of dried blood spots samples for the screening of hepatitis B virus surface by enzyme immunoassay method.

Dried Blood Spots (DBS) are blood collection carriers that facilitate the storage and transport of samples. Used for quality control during sero-epidemiological investigations, DBS eluate are not the conventional specimen indicated by manufacturers for enzyme immunoassay method (EIA) for hepatitis B virus surface (HBs antigen). The aim of our study was to evaluate DBS eluates used as a matrix for EIA of HBs antigen in a reference laboratory. This study took place from August 2016 to November 2017 at the Centre for Diagnosis and Research on AIDS and other infectious diseases (CeDReS) in Abidjan, Côte d'Ivoire. We used a panel of 149 whole blood samples from blood donors. The DBS performed with these samples were analyzed after elution with the HBsAg (version ULTRA) ELISA, Dia.Pro Diagnostic Bioprobes S.R.L., Sesto San Giovanni, Italy. The technical performance (sensitivity and specificity and kappa coefficient) of the test performed on DBS was determined for different ratios (optical density/threshold value) compared to the results obtained on the plasma used as reference. We obtained a sensitivity of 100% with DBS for all ratios. The specificity increased according to the ratio of optical density of the individual EIA reaction to the threshold value, with 6.09%, 47.0%, and 83.0%, respectively, for ratios of 1.0, 3.0, and 5.0. Best performance was observed at ratio of 10.0 with a sensitivity and specificity of 100%. In conclusion, DBS eluate can be used for the diagnosis of viral hepatitis B and would be useful for conducting sero-epidemiological investigations. However, ratio giving best performance must be determined for each enzyme immunoassay method kits.

Plasma sVCAM-1, antiretroviral therapy and mortality in HIV-1-infected West African adults.

OBJECTIVES: We report the association between pre-antiretroviral therapy (pre-ART) soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and long-term mortality in HIV-infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). METHODS: The ART-naïve HIV-infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow-up were invited to participate in a post-trial phase (PTP). The PTP end-point was all-cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM-1 and all-cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV-1 RNA and peripheral blood mononuclear cell HIV-1 DNA levels. RESULTS: In all, 954 adults (77% women, median CD4 count of 387 cells/µL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2-6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM-1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60-5.11]. The 6-year probability of death rates were 14.4% (95%CI: 9.1-22.6) and 9.4% (5.4-16.1) in patients with baseline sVCAM-1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2-6.5) and 3.5% (1.9-6.3) in patients with baseline sVCAM-1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre-ART and 12-month sVCAM-1 levels in patients randomized to immediate ART was -252 (IQR: -587 to -61). CONCLUSIONS: Pre-ART sVCAM-1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART.

Association of Plasma Soluble Vascular Cell Adhesion Molecule-1 and sCD14 With Mortality in HIV-1-Infected West African Adults With High CD4 Counts.

BACKGROUND: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. In this article, we report the association between 11 biomarkers and medium-term mortality in HIV-infected West African adults. METHODS: In Temprano ANRS 12136, antiretroviral therapy (ART)-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the World Health Organization criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a posttrial phase. The posttrial phase end point was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers [IL-1ra, IL-6, soluble vascular cell adhesion molecule 1 (sVCAM-1), sCD14, D-dimer, fibrinogen, IP-10, sCD163, albumin, high-sensitivity C-reactive protein, and 16S rDNA] and all-cause death in the Temprano participants randomized to defer ART. RESULTS: Four hundred seventy-seven patients (median age 35 years, 78% women, and median CD4 count: 379 cells/mm) were randomly assigned to defer starting ART until the World Health Organization criteria were met. The participants were followed for 2646 person-years (median 5.8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, peripheral blood mononuclear cell HIV-1 DNA, and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥1458 vs. <1458: adjusted hazard ratio 2.57, 95% confidence interval: 1.13 to 5.82) and sCD14 (≥2187 vs. <2187: adjusted hazard ratio 2.79, interquartile range 1.29-6.02) levels. CONCLUSIONS: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality.

Evaluation of Four Rapid Tests for Detection of Hepatitis B Surface Antigen in Ivory Coast.

BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. Hepatitis B surface antigen (HBsAg) rapid diagnostic tests (RDTs) could be an ideal tool for a large-scale HBV screening in settings with high endemicity but limited infrastructure. The aim of this study was to evaluate the diagnosis performance of such RDTs for screening HBV infection in Ivory Coast. METHODS: From September 2018 to January 2019, a cross-sectional phase I evaluation study of RDTs was conducted in three laboratories of Abidjan (CeDReS, CNTS and IPCI), on a panel of 405 whole blood samples and 699 plasmas. Four HBsAg RDTs (Determine™ HBsAg, SD Bioline HBsAg WB®, Standard Q HBsAg® and Vikia HBsAg®) were evaluated. The diagnostic performance (sensitivity and specificity) was calculated in comparison to the reference sequential algorithms of two EIA tests (Dia.Pro HBsAg® one version ULTRA and Monolisa™ HBsAg ULTRA). RESULTS: The Determine™ HBsAg and Vikia HBsAg® tests performed well, with 100% of sensitivity, specificity both on plasma and on whole blood. For SD Bioline HBsAg WB® and Standard Q HBsAg®, the specificities were 99.8% and the sensitivities 99.3% and 97.1% respectively. Finally, there were a total of 19 false negative results: 3 with SD Bioline HBsAg WB® and 16 with Standard Q HBsAg®. CONCLUSION: Determine HBsAg® from Alere and Vikia HBsAg® from Biomérieux are the most suitable RDTs for screening for HBV in Ivory Coast. A phase II evaluation must be initiated.

Evaluation of two (02) platforms for chemiluminescence-based detection of anti-rubella IgG antibodies in a sub-Saharan country, Côte d'Ivoire.

The diagnosis of rubella is mainly made in pregnant women and the newborn by specific IgG and/or IgM detection. In addition to HAI and ELISA techniques, new immunoanalytical methods have been developed. This study aimed to evaluate two chemiluminescence platforms, Architect i2000SR and Maglumi 800 for rubella biological diagnosis in Côte d'Ivoire. Blood samples were taken from 113 pregnant women aged 15 to 30 in prenatal care. Samples were analyzed for Rubella IgG detection at the NBTS laboratory on the evaluated platforms and the Cobas e601 used as a reference. The majority of women were in their second trimester of pregnancy. Among them, only 13.3% were vaccinated against rubella. The evaluated platforms showed good precision with coefficients of variation >10%. Regarding analytical performances, sensitivities were 97.53% and 96.29% whereas specificities were 100% and 96.88% for Architect I2000SR and Maglumi800, respectively. Both platforms showed good agreement with cobas e601 for antibody levels <200 IU/ml and <350UI/ml for Architect and Maglumi 800, respectively. Findings of the current study revealed that the two platforms have similar features with Cobas e601 and could be used routinely for the serological diagnosis of rubella. However, the results of one platform should not be extrapolated to another.

Hepatitis B treatment eligibility in West Africa: Uncertainties and need for prospective cohort studies.

BACKGROUND & AIMS: While universal screening of hepatitis B virus (HBV) is recommended in high burden countries, little is known about the proportion of HBV-infected persons in need of antiviral therapy in these settings. METHODS: Prisoners in Senegal and Togo as well as female sex workers and men who have sex with men in Cote d'Ivoire were screened for HBV infection. All HBsAg-positive participants underwent transient elastography, alanine aminotransferase (ALT) and HBV viral load (VL) quantification. Individuals with cirrhosis or those aged >30 years with an HBV replication ≥20 000 IU/mL and elevated ALT were considered eligible for antiviral therapy. RESULTS: Of 1256 participants, 110 (8.8%) were HBsAg positive; their median age was 30 years [interquartile range: 25-33] and 96 (86.5%) were men. Three individuals (2.7%) had cirrhosis, while 28 (29.5%) of 94 participants with available measurements had an HBV VL ≥20 000 IU/mL. Overall, 11 (10.0%) subjects were considered eligible for immediate antiviral treatment (2.1% of participants in Dakar, 7.7% in Abidjan and 21.6% in Lome, P=.001) and 59 (53.4%) for close monitoring due to the presence of significant liver fibrosis, elevated ALT or significant HBV replication. CONCLUSIONS: Among vulnerable populations in West Africa, a minority of HBV-infected individuals were eligible for immediate antiviral therapy. Prospective cohort studies are necessary to evaluate anti-HBV treatment eligibility facing the significant proportion of individuals with active chronic HBV infection.

Prevalence and risk factors associated with HIV and tuberculosis in people who use drugs in Abidjan, Ivory Coast.

BACKGROUND: The number of people who use drugs (PWUD) has dramatically increased in West Africa over the last 15 years, but targeted interventions are falling behind, notably because of the lack of awareness of the health needs of PWUD. We aimed to assess prevalence and factors associated with HIV and other infections in PWUD in Abidjan, Ivory Coast, one of the countries most affected by HIV in Western Africa. METHODS: We used respondent-driven-sampling to obtain a representative sample of heroin or cocaine/crack users aged 18 years or more. Socio-behavioral data were obtained by face-to-face questionnaires. Blood samples were collected and tested for HIV. Two sputa were obtained in tuberculosis (TB) symptomatic participants for acid-fast-bacilli (AFB) smear testing. After a descriptive analysis, crude prevalence were calculated, then weighted to take account of the sampling method. Factors associated with HIV and TB were studied using adjusted log-binomial regression. Population size was estimated by capture-recapture. RESULTS: 450 PWUD were recruited in May 2014. The mean age was 33.5 years; 10.9% were women. Smoking was the main mode of consumption, ever injecting was reported by 12.7% of the participants (3.6% in the past month). Sex work was reported by 15.8% of the PWUD (13.7% of the men), and 10.2% of the men reported sexual relationships with other men (MSM). We found a weighted prevalence of 9.5% for HIV. Women were 3.4 times more likely to be infected than men. Among men, being a sex worker (SW) (adjusted OR 2.9 [95CI 1.06-7.98]) or MSM (adjusted OR 11.5 [95CI 4.22-31.42]) were the main factors associated with HIV infection in adjusted analysis. Injection was not associated with HIV. TB weighted prevalence was 1.8%, associated with poor living arrangements in adjusted analysis. We estimated that 3521; 95CI 3049-3993 PWUD live in Abidjan. CONCLUSION: PWUD in Abidjan are at high risk of HIV due to sexual transmission, especially in women, SW and MSM who also use drugs. Interventions should be developed to improve HIV prevention and linkage to care in these specific populations. More generally, improving the health of PWUD involves a broader reflection on the living environment and access to health care of slum residents in large African cities.

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

Quantiferon-TB Gold: performance for ruling out active tuberculosis in HIV-infected adults with high CD4 count in Côte d'Ivoire, West Africa.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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: ClinicalTrials.gov NCT00495651.

Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of the West African Database to evaluate AIDS collaboration.

INTRODUCTION: West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. METHOD: A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d'Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d'Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot - Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). RESULTS: A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm(3) and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). CONCLUSIONS: Patients with HIV-2 mono-infection are correctly discriminated by the national algorithms used in West African countries. HIV-1&2 dually reactive patients should be systematically investigated, with a standardized algorithm using more accurate tests, before initiating ART as at least 4 out of 10 of them could initiate an effective first-line ART for HIV-1 and optimize their second-line treatment options.

Interest in Determining the CD34+ CD38- Phenotype in the Diagnosis and Prognosis of Acute Leukemia in Abidjan - Côte d'Ivoire.

BACKGROUND: In Côte d'Ivoire, acute leukemias account for 12.5% of hematological malignancies. Acute leukemias are due to an anomaly of the stem cell characterized among other things by the expression of CD34(+) CD38(-) surface markers. This CD34(+) CD38(-) phenotype as well as other factors such as tumor syndrome, high leukocytosis and blasts are considered as important factors of poor prognosis. We therefore proposed to investigate the prognostic value of the expression of CD34(+) CD38(-) markers in acute leukemias in Abidjan. METHODS: We selected 23 patients aged 33 years on whom we performed Complete Blood Count, bone marrow aspiration and immunophenotyping. To search for myeloperoxydase, smears of blood or bone marrow were stained with benzidine and revealed by the use of Hydrogen peroxide. Acute leukemias were then identified and distributed using the score proposed by the European Group for the Immunological characterization of Leukemias. The definitive diagnosis was made by combining morphological characters that serve as the basis for the French-American-British classification as well as cytochemical and immunophenotypic characters. RESULTS: According to the cytological and immunophenotypic classifications, the acute lymphoid leukemia 2 and B IV predominated. 52.2% (12/33) of patients were CD34(+) CD38(-). This phenotype was found in almost all cytological immunophenotypic types. The medullary invasion by blasts (reflection of the tumor mass) of the total sample of CD34(+), CD34(+) CD38(-) patients and those not expressing CD34(+) was respectively 79.4%, 81.25%, 83.3% and 74.8%. CONCLUSION: There was therefore no correlation between medullary blasts and the expression of CD34(+) CD38(-). To the factors we selected it would have been necessary to associate the study of cytogenetic and molecular anomalies to better understand the role of CD34(+) CD38(-) phenotype, concerning prognosis.

CD4 cell eligibility thresholds: an analysis of the time to antiretroviral treatment in HIV-1 seroconverters.

BACKGROUND: WHO recommends initiating combination antiretroviral treatment at the minimal CD4 cell threshold of 350 cells/µl. In sub-Saharan Africa, the time for a recently infected patient to reach this threshold is unclear. METHOD: We estimated the probability of reaching different CD4 cell thresholds over time in the ANRS 1220 cohort of HIV-1 seroconverters in Côte d'Ivoire. CD4 cell slopes were estimated using a mixed linear model. Probabilities of crossing the 350 and 500 cells/µl CD4 cell thresholds were estimated by the Kaplan-Meier method. RESULTS: Between 1997 and 2009, 304 recent seroconverters have been enrolled in the Primo-CI cohort (62% men, median baseline age 29 years and median time since the estimated date of seroconversion 9 months). The probability of having a first CD4 cell count below 500 cells/µl was 0.57, 0.72, 0.79 and 0.84 at study entry, 2, 4 and 6 years, respectively. For a first CD4 cell count below 350 cells/µl, 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 cells/µl and 7.0 years for 350 cells/µl.

Comparison of early CD4 T-cell count in HIV-1 seroconverters in Côte d'Ivoire and France: the ANRS PRIMO-CI and SEROCO cohorts.

OBJECTIVE: We compared CD4+ decline among untreated HIV-1-infected seroconverters living in Côte d'Ivoire (CI) and in France. METHODS: HIV-1-infected adults were enrolled in the ANRS1220 PRIMO-CI (CI, 1997-2006) and ANRSCO2 SEROCO (France, 1988-1995) cohorts. CD4+ count and percentage declines were estimated from enrollment until 24 months of seroconversion by linear random-effect models adjusted for time since seroconversion, age, gender, cell-associated HIV DNA, HIV RNA, and country. RESULTS: Overall 521 seroconverters (CI 148, 62% men; France 373, 77% men) were enrolled after a median of 7.6 months since seroconversion. Median follow-up duration was 12.7 months. Median age was 28 years. Median baseline CD4+ count was 472 and 560 cells per cubic millimeter, respectively. Median baseline HIV RNA was 4.4 and 4.0 log10 copies per milliliter and median HIV DNA was 3.0 and 2.8 log10 copies per 10(6) peripheral blood mononuclear cells, respectively. In adjusted models, CD4+ count and percentage at baseline were lower in CI than in France (P < 0.01), and the difference did not vary during follow-up (P = 0.55). Low HIV RNA and low HIV DNA at baseline were associated with higher CD4+ count at baseline. CONCLUSIONS: CD4+ count and percentage were lower in CI than in France. These differences were already observed during early infection and remained similar after adjustment.

Medium-term probability of success of antiretroviral treatment after early warning signs of treatment failure in West African adults.

West African adults with warning signs of failure of antiretroviral treatment (ART) at 6 months were assessed for the probability and factors associated with success at 36 months. After 6 months on ART, patients were included if they had a bad immunologic response (BIR) (month 6 CD4 count < pre-ART CD4 count + 50/mm(3)), incomplete virologic suppression (IVS) (month 6 plasma HIV-1 RNA >300 copies/ml), or both (Dual). They were followed for 30 months after inclusion. CD4 counts and HIV-1 RNA were measured every 3 months. We estimated the probability of reaching immunovirologic success (CD4 count >350/mm(3) and plasma HIV-1 RNA <300 copies/ml) and looked for determinants using Cox analysis. A total of 208 adults were included. Among patients in the IVS and Dual groups, 23% and 38% had at least one genotypic resistance mutation at month 6. The 36-month cumulative probability of immunovirologic success was 0.84 in BIR, 0.81 in IVS, and 0.67 in Dual (p = 0.02). Adjusting for CD4 count, viral load, ART regimen, and morbidity, patients who had no genotypic resistance mutations at month 6 or a medication possession ratio (MPR) >90% between month 6 and month 36 had a likelihood of success 3.8 and 3.6 higher than other patients. The 36-month probability of success was 0.56 and 0.86 in patients with an MPR <90% and >90% and 0.59 and 0.84 in patients with and without resistance. After warning signs of failure at 6 months, a large proportion of patients reaches immunovirologic success before 36 months provided there is a high rate of adherence to medication and the absence of early resistance mutations.

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.

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 (IC(50)) neutralization titers of >or=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 IC(50) 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.

Relationship of CD4+ T-cell counts and plasma HIV-1 RNA levels with serological HBeAg/anti-HBe patterns obtained in West-African HBV-HIV-1-co-infected children.

HBeAg/anti-HBe and hepatitis B virus (HBV) DNA from 34 HIV-1-infected children from Ivory Coast with chronic hepatitis B (CHB) were longitudinally analyzed according to CD4 and HIV-1 RNA. The mean CD4% value was significantly (p = 0.03) lower in 59 (52.7%) samples showing a usual CHB (HBeAg-positive/anti-HBe-negative and HBV DNA-positive), as compared with 30 (26.8%) HBeAg-positive/anti-HBe-positive and HBV DNA-positive and 23 (20.5%) HBeAg-negative/anti-HBe-positive and HBV DNA-negative (15.1% vs. 18.5% and 20.0%). The mean HIV-1 RNA concentrations were significantly (p = 0.01) higher in specimens HBV DNA-positive (4.47 and 4.30 log(10)/ml, respectively) vs. HBV DNA-negative (3.43 log(10)/ml). HIV-1 has a significant impact on CHB acquired in childhood.

Anthropometric and immunological success of antiretroviral therapy and prediction of virological success in west African adults.

OBJECTIVE: 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 measurement. We assessed the gain or loss in body mass index (BMI), alone or in combination with the gain or loss in CD4+ T-cell count (CD4), as a tool for predicting the response to ART. METHODS: In a cohort of 622 adults in Abidjan, Côte d'Ivoire, we calculated the sensitivity, specificity and predictive values of BMI and CD4 for treatment success defined as viral-load undetectability (< 300 copies/ml) as gold standard. FINDINGS: After 6 months of ART, the median change in BMI was an increase of 1.0 kg/m(2) (interquartile range, IQR: 0.0-2.1), the median change in CD4 an increase of 148/ml (IQR: 54-230) and 84% of patients reached viral-load undetectability. The distribution of change in BMI was similar among patients who reached undetectability and those who did not (increases of 1.06 kg/m(2) versus 0.99 kg/m(2), P = 0.51). With larger changes in BMI, the specificity for treatment success increased but its sensitivity decreased and its positive predictive value was stable around 85%. All results remained similar when combining changes in BMI with those in CD4 and when stratifying by groups of baseline BMI or CD4. CONCLUSION: In settings where viral-load measurement is not available, a high BMI gain does not reflect virological success, even when combined with a high CD4 gain. In our population, most patients with detectable viral-load had probably adhered to the drug regimen sufficiently to reach significant gains in body mass and CD4 count but had adhered insufficiently to reach viral suppression.

Frequent occurrence of chronic hepatitis B virus infection among West African HIV type-1-infected children.

BACKGROUND: The aim of this study, conducted in Ivory Coast, was to evaluate the prevalence and evolution of viral hepatitis in children coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: Hepatitis B virus (HBV) and hepatitis C virus (HCV) markers were retrospectively and longitudinally assessed among 280 HIV-1-infected children enrolled in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales B et C 1244/1278 cohort. Among these, 173 (61.8%) received highly active antiretroviral therapy (HAART), including lamivudine (3TC) for 122 children. Detection of the hepatitis B s antigen (HBsAg) was performed on specimens collected at inclusion and 6 months later. If results of both tests were positive, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) and HBV DNA levels were measured at inclusion and during follow-up. A fourth-generation HCV enzyme immunoassay was used for HCV screening at inclusion. RESULTS: In our pediatric cohort, no patients were infected with HCV, but the prevalence of HBsAg at inclusion was 12.1% (34 of 280; 95% confidence interval [CI], 8.6-16.6). Among the HBV-HIV-1-coinfected children, a high rate of positive HBeAg chronic hepatitis B (CHB) was noted at inclusion (82.4% [ 28 of 34]; 95% CI, 65.5%-93.2%) and after a median follow-up of 18 months (78.3%; 95% CI, 45.5%-92.7%), with no significant difference between children treated with HAART (with or without 3TC) and untreated ones. These children showed high HBV DNA levels (usually >8.0 log(10) copies/mL) and viral population consisting of nearly exclusively wild-type HBeAg-positive HBV strains, strongly suggesting that most of them were in the initial immunotolerant phase of chronic hepatitis B. CONCLUSION: In sub-Saharan Africa, children with chronic hepatitis B and who are treated with 3TC-based HAART are at risk of developing 3TC resistance. Further studies are required to guide the management of HBV-HIV-1-coinfected children.