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Background: In 2015, Togo introduced the "test-and-treat" strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Pediatric HIV infection remains a public health problem in Togo, with a mother-to-child transmission (MTCT) rate of 3.6% in 2020. This study aimed to estimate cases of HIV seroconversion during pregnancy and to identify pregnant women at high risk of transmitting HIV to their children in Lomé, Togo., Methods: A descriptive cross-sectional study was carried out from 18 March to 22 May 2022 among women who had given birth in five maternity units providing PMTCT services in Lomé. Umbilical cord blood samples were taken from the maternal side by midwives after delivery. HIV serology was performed in the laboratory using the Alere™ HIV Combo SET and First Response HIV 1-2. Card Test version 2.0. A sample was considered positive if both tests were positive. The HIV-1 viral load in HIV-1-positive samples was measured using Cobas/Roche 4800 equipment. Information on the women was extracted from maternal antenatal records and antenatal consultation registers., Results: A total of 3148 umbilical cord blood samples (median maternal age: 28 years (interquartile range [24-32]) were collected. Among them, 99.3% (3145/3148) had presented for at least one antenatal clinic visit before giving birth, and 78.7% (2456/3122) had presented for at least four visits. One hundred and twenty-one (121) cord samples were HIV-1 positive, representing a seroprevalence of 3.8% (95% CI = [3.2-4.6]). Among them, 67.8% (82/121) were known HIV-positive before the current pregnancy, 29.7 (36/121) were diagnosed as HIV-positive at the antenatal visits and 2.5% (3/121) were diagnosed as HIV-positive in the delivery room. Of the HIV-positive women, 85.9% (104/121) were on ARV treatment before delivery. The viral load was < 1000 copies/ml in 97.5% (118/121) cases., Conclusion: This study explored the virologic and epidemiological aspects of HIV among pregnant women in Togo. The results show significant viral suppression at delivery in women ART. Surveillance based on umbilical cord blood specimen screening is an interesting approach for monitoring the effectiveness of PMTCT programmes., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tchounga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target., Methods: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme., Results: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.80 0.56 ), with uncertainty range 85.5-90.6% (0.80 0.70 -0.80 0.44 )., Conclusions: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: The presence of the human leukocyte antigen HLA-B*57:01 is associated with the development of a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*57:01 prevalence in individuals with HIV-1 in Africa. This study aimed to estimate HLA-B*57:01 prevalence in individuals with HIV-1 in West and Central Africa., Methods: A cross-sectional study was conducted in four countries in West and central Africa (Burkina-Faso, Côte d'Ivoire, Gabon, and Togo) from January 2016 to February 2020 to determine the status of HLA-B*57:01 in adults with HIV-1. The presence of HLA-B*57:01 was determined by using Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) in blood samples. Prevalence rates were stratified based on country., Results: A total of 4016 (69.8% women) individuals with HIV were enrolled. Their median age was 45, and the interquartile range was 38-52. We included 500 (12.4%) patients in Burkina-Faso, 1453 (36.2%) in Côte d'Ivoire, 951 (23.7%) in Gabon, and 1112 (27.7%) in Togo. The overall HLA-B*57:01 prevalence was 0.1% [95% CI: 0.0-0.2%]. The prevalence of HLA-B*57:01 was similar according to the four countries. Only one case was reported in each country except Togo, with no cases., Conclusions: HLA-B*57:01 prevalence is low in individuals with HIV in West and central Africa, and there is no difference among countries. This study does not confirm the utility of HLA-B*57:01 allele testing for abacavir use in this region., (© 2021. The Author(s).)

Understanding the HIV epidemic in key populations is important. Today only scarce information is available on HIV-1 strains that circulate in men having sex with men (MSM) in sub-Saharan Africa. Here, we studied for the first time the genetic diversity of HIV-1 strains circulating in the MSM population in Lomé, the capital city from Togo. The overall subtype/CRF distribution in pol (protease and/or partial reverse transcriptase (RT)) among the 79 HIV-1 strains from MSM was as follows: CRF02&#95;AG (72%, n=57), subtype G (2.5%, n=2), sub-subtype A3 (1.3%, n=1), and unique recombinant forms (URF) (24%, n=19). Among the 19 URFs four different mosaic structures were observed, annotated as URF1 to URF4. Fifteen sequences (URF1) had the same mosaic structure in pol (G/CRF02&#95;AG) and could represent a new circulating recombinant form (CRF). Phylogenetic analysis of the RT sequences showed that there were several introductions of CRF02&#95;AG strains in the MSM population, however half of the CRF02&#95;AG and all URF1 strains formed a separate, well-supported cluster suggesting one major introduction of CRF02&#95;AG in the MSM population followed by efficient transmission and emergence of a possible new CRF. At least 40% of the strains fell into recent transmission chains involving two to seven MSM. Comparison with >950 HIV-1 sequences from previous studies in Togo showed intermixing of the HIV-1 epidemics between MSM and the general population. Moreover, an HIV-1 strain from a recently HIV-1 infected male patient from Germany, fell within a cluster of HIV-1 strains from MSM from Togo, illustrating recent exchange between MSM from Africa and people from other geographic regions. With growing evidence of the importance of MSM in the dynamic of the HIV epidemic in Africa there is an urgent need for appropriate interventions to limit HIV transmission in this population group., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Prevention of mother-to-child transmission (PMTCT) programs have been largely scaled-up, but data on infant HIV drug resistance from PMTCT programs implemented in resource-limited countries are lacking., Methods: Remnant dried blood spots from HIV-infected children (aged <18 months) tested through the Togo national early infant diagnosis program during 2012 and 2013 were collected and assessed for HIV drug resistance. Pol-RT (reverse transcriptase) region was amplified, sequenced and analyzed for the presence of drug resistance mutations (DRMs)., Results: Overall, 121 of 201 (60.2%) newly diagnosed children had detectable DRMs. Among the 131 of 201 (65.2%) children with reported exposure to maternal and/or infant antiretrovirals (ARVs), DRMs were detected in 99 children (75.6%). Importantly, in 41 of 201 children for whom no exposure to ARVs was reported, DRMs were detected in 11 children (26.8%). For 29 children, no data on ARV exposure were available. For the 121 of 201 children with DRMs, 99 of 121 (81.8%) had only nonnucleoside reverse transcriptase inhibitor DRMs detected but 21 of 121 (17.3%) had both nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) DRMs. Among breast-fed children, drug resistance was more frequent when mothers were on antiretroviral therapy (ART), 61 of 75 (81.3%) versus 14 of 39 (35.9%) when mothers were not on ART (P < 0.001). Nucleoside reverse transcriptase inhibitor resistance was more common when mothers were on ART., Conclusions: Scale-up and improvement of PMTCT strategies resulted in a global decrease of pediatric HIV infections, but our study shows high rates of drug resistance in infants for whom prevention failed.

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.

Background: HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA)., Methods: We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region., Results: Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3)., Conclusions: This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

Objective: To compare the lymphocyte T CD4+ (CD4) response to combinations of antiretroviral therapy (ART) in HIV-1, HIV-2 and dually positive patients in West Africa., Design and Setting: Collaboration of 12 prospective cohorts of HIV-infected adults followed in Senegal (2), Gambia (1), Mali (2), Benin (1) and Côte d'Ivoire (6)., Subjects: Nine thousand, four hundred and eighty-two patients infected by HIV-1 only, 270 by HIV-2 only and 321 dually positive, who initiated an ART., Outcome Measures: CD4 change over a 12-month period., Results: Observed CD4 cell counts at treatment initiation were similar in the three groups [overall median 155, interquartile range (IQR) 68; 249 cells/microl). In HIV-1 patients, the most common ART regimen was two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI; N = 7714) as well as for dually positive patients (N = 135). HIV-2 patients were most often treated with a protease inhibitor-based regimen (N = 193) but 45 of them were treated with an NNRTI-containing ART. In those treated with a NNRTI-containing regimen, the estimated mean CD4 change between 3 and 12 months was significantly lower in HIV-2 (-41 cells/microl per year) and dually positive patients (+12 cells/microl per year) compared to HIV-1 patients (+69 cells/microl per year, overall P value 0.01). The response in HIV-2 and dually positive patients treated by another regimen (triple NRTIs or protease inhibitor-containing ART) was not significantly different than the response obtained in HIV-1-only patients (all P values >0.30)., Conclusion: An optimal CD4 response to ART in West Africa requires determining HIV type prior to initiation of antiretroviral drugs. NNRTIs are the mainstay of first-line ART in West Africa but are not adapted to the treatment of HIV-2 and dually positive patients.

Prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves and are also infrequently used. Furthermore, postnatal transmission via breast-feeding is a serious additional threat. Modifications of infant feeding practices aim to reduce HIV-1 transmission through breast milk; replacement feeding is neither affordable nor safe for the majority of African women, and early breast-feeding cessation (eg, prior to 6 months of life) requires substantial care and nutritional counseling to be practiced safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breast-feeding women, with good efficacy, or single-drug postexposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate pediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-1-infected women through pregnancy, delivery, and the entire breast-feeding period. On the basis of available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay.

Background: Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described., Methods: HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model., Results: Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/microl) and 151 received HAART (median CD4 cell count 182 cells/microl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10-7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15-4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20-4.91) were associated with LBW., Conclusion: HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW.

Objective: Our aim was to study the response to antiretroviral treatment among women exposed to single-dose nevirapine (NVP) and/or short-course zidovudine (ZDV; with or without lamivudine [3TC]) for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection., Methods: All HIV type 1-infected women who initiated antiretroviral treatment with stavudine or ZDV, 3TC, and NVP or efavirenz were eligible for the MTCT-Plus program in Abidjan, Ivory Coast. Exposed women had received either single-dose NVP alone or short-course ZDV (with or without 3TC) plus single-dose NVP during previous pregnancy. Genotypic resistance testing was performed at week 4 after delivery. Virologic failure was defined as a plasma HIV RNA level >500 copies/mL 12 months after initiation of antiretroviral treatment., Results: Among 247 women who received antiretroviral treatment, 109 (44%) were unexposed; 81 had received short-course ZDV with 3TC, as well as single-dose NVP; 5 had received short-course ZDV plus 3TC; 50 had received short-course ZDV plus single-dose NVP; and 2 had received single-dose NVP alone. No ZDV mutation was detected in the 115 women whose specimens were available for genotypic testing; 11 (15.1%) of 73 women with 3TC exposure who were tested after delivery had 3TC resistance mutations. Three (4.3%) of 69 women exposed to short-course ZDV and 3TC plus single-dose NVP and 16 (38.1%) of 42 women exposed to short-course ZDV plus single-dose NVP had NVP resistance mutations. Antiretroviral treatment was initiated a median of 21 months after the intervention to prevent mother-to-child HIV transmission (median CD4(+) T lymphocyte count, 188 cells/mm(3)). Month 12 virologic failure was identified in 42 (19.2%) of 219 women for whom data were available, and multivariate analysis revealed that it was associated with poor adherence to treatment (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 3.0-53.9), postpartum 3TC resistance mutations (aOR, 6.9; 95% CI, 1.1-42.9), and a baseline CD4(+) T lymphocyte count <200 cells/mm(3) (aOR, 0.3; 95% CI, 0.2-0.8). NVP resistance was not associated with virological failure (aOR, 1.8; 95% CI, 0.5-6.5)., Conclusions: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.

We studied whether the use of T-lymphocyte CD4 (CD4) absolute count instead of CD4 percentage could affect the decision process regarding HAART initiation in African HIV-infected pregnant women. A prospective cohort in Abidjan, Côte d'Ivoire before HAART was available. Participating women received a perinatal antiretroviral prophylaxis (zidovudine + single-dose of nevirapine). CD4 count and percentage were measured by flow cytometry at baseline (32 weeks of amenorrhea) and at 1 month after delivery. A signed-rank test was used to compare the distributions of the CD4 absolute count and percentage values. A total of 325 HIV-1-infected pregnant women were included. At baseline, their median CD4 count was 355 cells/mm(3) and the median CD4 percentage was 24.8%; 17.8% of women had a CD4 count <200 cells/mm(3) and 14.8 % had a CD4 percentage <15%. One month after delivery, the median CD4 count was 489 cells/mm(3) (vs. baseline: p < 0.001), the median CD4 percentage was 25.6% (vs. baseline: p = 0.107), 9.5% of women had CD4 count <200 cells/mm(3) (vs. baseline: p < 0.001), and 15.1% of women had a CD4 percentage <15% (vs. baseline: p = 0.823). When combining the CD4 count and the WHO clinical stage, the proportion of women who met the WHO 2006 criteria for initiating HAART was 28.3% at baseline but 17.2% only at 1 month after delivery (p < 0.001). Between the prepregnancy and the postdelivery periods, the CD4 count experienced a significant increase, whereas the CD4 percentage remained unchanged. To accurately target the most appropriate time to start HAART, the CD4 percentage could be more reliable than the absolute count in sub-Saharan African pregnant women.

Background: Single-dose nevirapine (NVP) is the main option for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of single-dose NVP results in HIV-1 viral resistance which could compromise the success of subsequent treatment of mother and child with antiretroviral combinations that include non-nucleosidic-reverse-transcriptase inhibitors. This systematic review and meta-analysis of summarized data aimed to estimate the proportion of mothers and children with NVP resistance mutations detected in plasma samples 4-8 weeks postpartum after single-dose NVP use for PMTCT., Methods: Systematic search of electronic databases (MEDLINE, PASCAL) and conference proceedings (1997 to February 2006). Inclusion of all studies, without design, place or language restrictions, meeting the following criteria: use of single-dose NVP; viral genotyping performed with standard sequence analyses, between 4 and 8 weeks postpartum, in plasma samples; available public report; report of mothers' median baseline plasma HIV-1 RNA levels. Data extraction by two independent reviewers using a standardized form created for this purpose. Logistic random effect models to obtain pooled estimates. Univariable and multivariable meta-regression to explore sources of heterogeneity., Results: The pooled estimate of NVP resistance prevalence was 35.7% [95% confidence interval (CI) 23.0-50.6] in women in 10 study arms using single-dose NVP +/- other antepartum antiretrovirals and 4.5% (CI 2.1-9.4) in three study arms providing also postpartum antiretrovirals (adjusted odds ratio 0.08; CI 0.04-0.16). The corresponding estimates in children were 52.6% (CI 37.7-67.0) in seven study arms using single-dose NVP only and 16.5% (CI 8.9-28.3) in eight study arms combining single-dose NVP with other antiretrovirals., Conclusions: Single-dose NVP is widely used for PMTCT in resource-poor settings, but the burden of viral resistance is high in both women and children. It is substantially lower in studies providing additional postpartum antiretrovirals. The clinical implications of these findings should be further investigated.

The high genetic diversity of HIV-1 has a major impact on the quantification of plasma HIV-1 RNA, representing an increasingly difficult challenge. A total of 898 plasma specimens positive for HIV-1 RNA by commercial assays (Amplicor v1.5; Roche Diagnostic Systems, Alameda, CA or Versant v3.0; Bayer Diagnostics, Emeryville, CA) were tested using the Agence Nationale de Recherches sur le SIDA second-generation (G2) real-time reverse transcriptase polymerase chain reaction (RT-PCR) test: 518 samples containing HIV-1 of known subtype, including 88 from 2 subtype panels and 430 harboring B (n = 266) and non-B (n = 164) group M HIV-1 subtypes from patients followed up in 2002 through 2005 at Necker Hospital (Paris, France), and 380 samples from 10 different countries (Argentina, Cambodia, Cameroon, Central African Republic, France, Ivory Coast, Madagascar, Morocco, Thailand, and Zimbabwe). HIV-1 RNA values obtained by G2 real-time PCR were highly correlated with those obtained by the Amplicor v1.5 for B and non-B subtypes (R = 0.892 and 0.892, respectively) and for samples from diverse countries (R = 0.867 and 0.893 for real-time PCR vs. Amplicor v1.5 and real-time PCR vs. Versant v3.0, respectively). Approximately 30% of specimens harboring non-B subtypes were underquantified by at least -0.51 log10 in Amplicor v1.5 versus 5% underquantified in G2 real-time PCR. Discrepant results were also obtained with subtype B samples (14% underquantified by Amplicor v1.5 vs. 7% by G2 real-time PCR). Similar percentages were observed when comparing results obtained with the G2 real-time PCR assay with those obtained using the Versant assay. Addressing HIV-1 diversity, continual monitoring of HIV-1 RNA assays, together with molecular epidemiology studies, is required to improve the accuracy of all HIV RNA assays.

Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on mothers' plasma samples at week 4 postpartum (PP) and on human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC) when an NVP resistance mutation was detected. The same tests were performed for the infected children at week 4, month 3, and month 12. Mothers' NVP plasma concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851 ng/ml for the mothers harboring NVP-R virus (P = 0.014). NVP-R mutations were detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in 6 of 26 infected children at week 4. All 6 children had detectable NVP-R mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month 12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells. Emergence of NVP-R virus in mothers is strongly correlated with a high level of plasma NVP concentration, owing to a prolonged postpartum period of viral replication under NVP selective pressure. The follow-up of the cohort demonstrates the prolonged archive of resistant virus.

The early diagnosis of pediatric HIV-1 infection is a critical issue in resource-limited settings to prioritize eligibility for antiretroviral therapy among HIV-1-infected children. A case-control study was performed within the ANRS 1201/1202 Ditrame Plus cohort (Abidjan, Côte d'Ivoire) to assess the usefulness of CD4+ T-cell percentage (CD4%) and total lymphocyte count (TLC) measured early in life in African children born to HIV-1-infected mothers. Using plasma HIV-1 RNA testing at 4 weeks of life as gold standard, CD4% and TLC were determined at month 3 and 6 in all 33 children HIV-1-infected in utero or intrapartum/early postpartum (cases) born to mothers receiving peripartum antiretroviral prophylaxis. Controls were 66 HIV-1-uninfected children from the same cohort. At month 3, the median CD4% was significantly lower in HIV-1-infected children (17.7%, 95% percentiles, 7.1-27.4) than in uninfected controls (34.8%, 18.5-45.3) (P < 0.001). A comparable difference was also observed at month 6. At the same time points, no significant difference was measurable for TLCs. The best threshold differentiating HIV-infected and uninfected children at month 3 was 25% CD4+. Compared to HIV-1 RNA results, sensitivity of this marker was 87.1% (95% confidence interval, 70.2-96.4) at month 3 and 88.9% (70.8-97.6) at month 6. Specificity was 78.3% (63.6-89.0) and 88.3% (77.4-95.2), respectively. Early CD4% measurement allows one to classify adequately the vast majority of exposed children according to their HIV status. CD4% should be further evaluated under field conditions for the diagnosis of pediatric HIV-1 infection and the monitoring of pediatric antiretroviral therapy.

The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis (P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1 transmission and minimizes the development of NVP resistance.

There is an urgent need for low-cost human immunodeficiency virus type 1 (HIV-1) viral load (VL) monitoring technologies in resource-limited settings. An automated TaqMan real-time reverse transcription-PCR (RT-PCR) assay was transferred to the laboratory of the Centre de Diagnostic et de Recherches sur le SIDA, Abidjan, Côte d'Ivoire, and assessed for HIV-1 RNA VL testing in 806 plasma samples collected within four ANRS research programs. The detection threshold and reproducibility of the assay were first determined. The quantitative results obtained with this assay were compared with two commercial HIV-1 RNA kits (the Versant version 3.0 and Monitor version 1.5 assays) in specimens harboring mainly the circulating recombinant form 02 strain (CRF02). The clinical evaluation of this test was done in different situations including the early diagnosis of pediatric infection and the monitoring of antiretroviral-treated patients. The quantification limit of our method was 300 copies/ml. The HIV-1 RNA values obtained by real-time PCR assay were highly correlated with those obtained by the Versant kit (r = 0.901; P < 0.001) and the Monitor test (r = 0.856; P < 0.001) and homogeneously distributed according to HIV-1 genotypes. For the early diagnosis of pediatric HIV-1 infection, the sensitivity and specificity of the real-time PCR assay were both 100% (95% confidence intervals of 93.7 to 100.0 and 98.3 to 100.0, respectively), compared to the Versant results. Following initiation of antiretroviral treatment, the kinetics of HIV-1 RNA levels were very comparable, with a similar proportion of adults and children below the detection limit during follow-up with our technique and the Versant assay. The TaqMan real-time PCR (12 dollars per test) is now routinely used to monitor HIV-1 infection in our laboratory. This technology should be further evaluated in limited-resource countries where strains other than CRF02 are prevalent.

Objectives: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations., Design: An open-label intervention cohort in Abidjan., Methods: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population., Results: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd)., Conclusions: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.

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.