Programme PAC-CI

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/mul and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrollment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.

BACKGROUND: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. METHODS AND FINDINGS: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. CONCLUSIONS: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.

BACKGROUND: As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed. METHODS: We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Côte d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy. RESULTS: Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S. dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen. CONCLUSIONS: A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources.

In November 1994 after 15 years of epidemiologic silence, Ebola virus reemerged in Africa and, for the first time, in West Africa. In Côte d'Ivoire, a 34-year-old female ethologist was infected while conducting a necropsy on a wild chimpanzee. Eight days later, the patient developed a syndrome that did not respond to antimalarial drugs and was characterized by high fever, headache, chills, myalgia, and cough. The patient had abdominal pain, diarrhea, vomiting, and a macular rash, and was repatriated to Switzerland. The patient suffered from prostration and weight loss but recovered without sequelae. Laboratory findings included aspartate aminotransferase and alanine aminotransferase activity highly elevated, thrombocytopenia, lymphopenia, and, subsequently, neutrophilia. A new subtype of Ebola was isolated from the patient's blood on days 4 and 8. No serologic conversion was detected among contact persons in Côte d'Ivoire (n = 22) or Switzerland (n = 52), suggesting that infection-control precautions were satisfactory.

In response to the HIV/AIDS pandemic in sub-Saharan Africa the African networks of IeDEA (International epidemiologic databases to Evaluate AIDS) aim to inform the scale-up of ART in the region through clinical and epidemiologic research. Funded by the National Institutes of Allergy and Infectious Diseases (NIAID) the objectives across the four African IeDEA regions (West Africa Central Africa East Africa and Southern Africa) are similar and cover all populations including pregnant women infants children adolescents and adult patients. They can be summarized as follows: (1) To prove robust evaluation of the delivery of ART in children adolescents and adults in sub-Saharan Africa with a focus on long-term program effectiveness and outcomes; (2) to describe the long-term temporal trends in regimen durability and tolerability and to examine monitoring strategies; (3) to describe important comorbidities and co-infections of HIV infection including malaria tuberculosis and cancer; (4) to examine the pregnancy- and HIV-related outcomes of women initiating ART during pregnancy and of infants exposed to HIV or ART in utero; (5) to develop and apply novel statistical methods to deal with missing data loss to follow-up competing risks and time-dependent confounding; (6) to establish procedures to link the HIV cohort data with other databases at local or national level. The present report provides an indicative summary of some of the major research themes and key findings as well as a discussion of the program’s strengths and weaknesses.

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

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.

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.

BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

BACKGROUND: To date, there is no effective treatment for COVID-19, which is a pandemic disease, caused by a novel coronavirus called SARS-CoV-2. In Togo, where four in five people practice self-medication, the absence of a cure for COVID-19 and the constant progression of the disease requires an assessment of self-medication patterns in the context of the pandemic. This study aimed to estimate the prevalence of self-medication to prevent COVID-19 and its associated factors in Lomé, Togo. METHODS: A cross-sectional study was conducted in Lomé, the capital city of Togo, from April 23rd to May 8th, 2020, with a sample of participants from five sectors: the healthcare, air transport, police, road transport and informal sectors. The participants were invited to provide information about their self-medication practices to prevent COVID-19 in the 2 weeks preceding the survey. RESULTS: A total of 955 participants (71.6% men) with a median age of 36 (IQR 32-43) were included. Approximately 22.1% were in the air transport sector, 20.5% were in the police sector, and 38.7% were in the health sector. The overall prevalence of self-medication to prevent COVID-19 was 34.2% (95% CI: 31.2-37.3%). The most commonly used products were vitamin C (27.6%) and traditional medicine (10.2%). Only 2.0% of participants reported using chloroquine/hydroxychloroquine. Female sex (aOR=1.90; p< 0.001), work in the health sector (aOR=1.89; p= 0.001), secondary education level (aOR= 2.28; p= 0.043) and university education level (aOR= 5.11; p< 0.001) were associated with self-medication. CONCLUSION: One-third of the individuals in high-risk populations in Lomé practiced self-medication. Intensifying awareness campaigns is crucial to fight misinformation about alleged COVID-19 prevention products on social media.

BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations. METHODS AND FINDINGS: Pre-dose drug concentrations were collected at Day-2 and Day-4 of treatment in 66 patients of the JIKI trial and compared to those predicted by the model taking into account patient's individual characteristics. At Day-2, the observed concentrations were slightly lower than the model predictions adjusted for patient's characteristics (median value of 46.1 versus 54.3 μg/mL for observed and predicted concentrations, respectively, p = 0.012). However, the concentrations dropped at Day-4, which was not anticipated by the model (median values of 25.9 and 64.4 μg/mL for observed and predicted concentrations, respectively, p<10-6). There was no significant relationship between favipiravir concentrations and EBOV viral kinetics or mortality. CONCLUSIONS: Favipiravir plasma concentrations in the JIKI trial failed to achieve the target exposure defined before the trial. Furthermore, the drug concentration experienced an unanticipated drop between Day-2 and Day-4. The origin of this drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. Dose-ranging studies should be performed in healthy volunteers to assess the concentrations and the tolerance that could be achieved with high doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.

OBJECTIVE: To describe the effect of highly active antiretroviral therapy (HAART) in HIV-1-infected African children. STUDY DESIGN: Observational ANRS 1244 cohort of 159 children with HIV between October 2000 and September 2002; 78 children (49%) receiving HAART were followed for a mean duration of 21 months. METHODS: Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), CD4 lymphocyte count and HIV-1 RNA viral load were measured before initiating HAART and every 6 months during treatment. Probability of survival and incidences of pneumonia and acute diarrhoea were calculated. RESULTS: Values before and after 620 days of HAART, respectively, were -2.02 and -1.39 for mean WAZ, (P < 0.01); -2.03 and -1.83 for mean HAZ (P = 0.51); 0.07 and 0.025/child-month (P = 0.002) for incidence of pneumonia; and 0.12 and 0.048/child-month for incidence of acute diarrhoea (P < 0.001) (incidence changes statistically significant only in children < 6.5 years). Overall, the probability of survival under HAART was 72.8% at 24 months for children with < 5% CD4 cells versus 97.8% in children with >/= 5% (P < 0.01). At HAART initiation, median viral load and CD4 cell percentage were 5.41 log10 copies/ml and 7.7%, respectively. After 756 days of HAART, on average, 50% of patients had undetectable viral load and 10% had 2.4-3.0 log10 copies/ml. The median CD4 percentage was 22.5%. CONCLUSION: In resource-limited setting, it is possible to use HAART to treat African children. This treatment appears as effective as in developed countries.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: =0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS).

OBJECTIVE: To assess the 24 month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission (MTCT) of HIV-1 in a breastfeeding population in West Africa. METHODS: Data were pooled from two clinical trials: DITRAME-ANRS049a conducted in Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina-Faso and RETRO-CI, conducted in Abidjan. Between September 1995 and February 1998, consenting HIV-1-seropositive women were randomly assigned to receive zidovudine (300 mg) or placebo: one tablet twice daily from 36-38 weeks' gestation until delivery, then in DITRAME only, for 7 more days. Paediatric HIV-1 infection was defined as a positive HIV-1 polymerase chain reaction, or if aged > or =15 months, a positive HIV-1 serology. Cumulative risks (CR) of infection were estimated using a competing risk approach with weaning as a competing event. RESULTS: Among 662 live-born children, 641 had at least one HIV-1 test. All but 12 children were breastfed. At 24 months, overall CR of MTCT were 0.225 in the zidovudine and 0.302 in the placebo group, a 26% significant reduction. Among children born to women with CD4 cell counts < 500/ml at enrollment, CR of MTCT were similar, 0.396 in the zidovudine and 0.413 in the placebo group. Among children born to women with CD4 cell counts > or =500/ml, CR of MTCT were 0.091 in the zidovudine and 0.220 in the placebo group, a significant 59% reduction. CONCLUSION: A maternal short-course zidovudine regimen reduces MTCT of HIV-1 at age 24 months, despite prolonged breastfeeding. However, efficacy was observed only among women with CD4 cell counts > or =500/ml. New interventions should be considered to prevent MTCT, especially for African women with advanced HIV-1 immunodeficiency.

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.

BACKGROUND: Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens. METHODS AND FINDINGS: The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged > or = 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%-9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age week 4 wk and 11.7% (95% CI 7.5%-15.9%) at 12 mo. CONCLUSIONS: This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.

A retrospective survey estimating the prevalence of hepatitis viruses B (HBV) and C (HCV) was conducted on samples taken in 1,002 African pregnant women (501 diagnosed as HIV-1 positive and 501 HIV-1 negative) participating in a clinical trial program conducted in Abidjan, Côte d'Ivoire (West Africa). Hepatitis B markers studied were HBs antigen (HBsAg), and if positive, HBe antigen/anti-HBe antibodies and HBV DNA. Two third generation (G3) HCV enzyme immunoassays (EIAs) were used for primary HCV screening. All anti-HCV antibody-positive sera were assessed further with supplementary assays (one another G3 EIA, RIBA 3.0, and HCV RNA). HCV genotypes were also determined. HBsAg was found in a similar proportion among HIV-positive (45/499, 9.0%, 95% confidence interval [95% CI], 6.6-11.9) and HIV-negative (40/498, 8.0%, 95% CI, 5.8-10.8) women (P = 0.58). The diagnosis of chronic hepatitis B, based on HBV DNA positive results, was more frequent in HIV-positive women (26.7%), compared to HIV-negative women (9.4%) (P = 0.06). In the case of hepatitis C infection, after supplementary testing allowing the elimination of frequent false-positive screening results, a prevalence rate of about 1% was found, both in HIV-positive (6/501, 1.2%, 95% CI, 0.44-2.59) and HIV-negative (4/501, 0.8%, 95% CI, 0.22-2.03) women (P = 0.53). Of the 10 samples confirmed positive and assessed for HCV RNA, eight (80%) were viraemic and belonged to HCV genotypes 1 or 2. The relative high frequency of HIV/HBV coinfection in Côte d'Ivoire emphasises the need for monitoring the risk of hepatotoxicity by antiretroviral therapy in such patients. We propose an accurate and cost-efficient algorithm for HCV diagnosis in Africa.

BACKGROUND: To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire. METHODS AND FINDINGS: We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16). CONCLUSIONS: cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.

The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.

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.