François Rouet

Highly active antiretroviral therapies among HIV-1- infected children in Abidjan, Cote d'Ivoire

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.

Impact of Hiv-1 Genetic Diversity on Plasma Hiv-1 Rna Quantification: Usefulness of the Agence Nationale de Recherches sur le Sida Second-generation Long Terminal Repeat-based Real-time Reverse Transcriptase Polymerase Chain Reaction Test

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 (R2 = 0.892 and 0.892, respectively) and for samples from diverse countries (R2 = 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.

Low Risk of Nevirapine Resistance Mutations in the Prevention of Mother-to-Child Transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Côte d'Ivoire

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.

Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission.

BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV‐C)/hepatitis G virus (HGV) infection showed a high prevalence of asymptomatic carriers in blood donors and in populations at risk for blood‐borne viruses. However, by using only viral RNA polymerase chain reaction, those studies underestimated the true spread of GBV‐C/HGV infection. The combined detection of GBV‐C/HGV RNA and of anti‐E2 (which reflects recovery from infection) is necessary to define accurately the prevalence of GBV‐C/HGV.

Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Côte d'Ivoire

Objective: To estimate the frequency of human immunodeficiency virus type 1 (HIV-1) displaying genotypic drug resistance in highly active antiretroviral therapy (HAART)-treated children in Abidjan. Methods: Among the 269 HIV-1-infected children enrolled in the ANRS 1278 prospective observational cohort between October 2000 and September 2003, 115 [median age, 6.35 years (range, 1.2–15)] required treatment and received HAART for at least 6 months. Treatment consisted of 2 nucleoside analogue reverse transcriptase inhibitors associated with nelfinavir (70.5%) or efavirenz (29.5%). Plasma HIV-1 RNA and CD4+ T cell counts were determined at baseline and every 6 months thereafter. Genotypic resistance tests were performed in cases of virologic failure (viral load ≥3 log10 copies/mL) after at least 6 months of HAART. Results: After a median of 10.2 months of HAART, 66% (76 of 115) of children were in virologic success. Most of these children were infected with CRF02 strains. Twenty-seven viruses displayed resistance to at least 1 antiretroviral drug (27 of 38, 71%). Thirteen, 9 and 5 children had viruses with resistance to 1, 2 or 3 of the drugs included in their regimen, respectively. Resistance to lamivudine and/or to non-nucleoside analogue reverse transcriptase inhibitors was frequent among the 38 children in virologic failure. The 90M, 46L, 88S or 54V mutations were found in 11 (38%) of the 29 children taking nelfinavir. The overall frequency of viruses showing genotypic resistance to at least 1 antiretroviral drug was 23% (27 of 115) among the treated children. Conclusion: These results are similar to what is generally observed in industrialized countries. Despite these encouraging results, efforts are needed to maximize the long-term efficiency of treatment and to minimize the risk of emergence of drug resistance in treated children.

Acceptability and uptake of a package to prevent mother-to-child transmission using rapid HIV testing in Abidjan, Côte d'Ivoire.

The participation of HIV-1-infected pregnant women in a programme of prevention of mother-to-child transmission (MTCT) of HIV in Abidjan is described. Prenatal counselling with a rapid HIV test was proposed to 14 067 pregnant women and acceptance was 89.4%. The return rate for results was 74.2%. The HIV-1 prevalence was 11.1% and 26.2% of HIV-infected women started the prevention of MTCT programme. To increase the uptake we recommend community mobilization and the strengthening of male involvement. (authors)

Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses

BACKGROUND: The routes of transmission of human herpes virus 8 (HHV‐8) remain unclear. In particular, HHV‐8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti‐HHV‐8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV‐8 transmission.

Tolerance and Acceptability of an Efavirenz-based Regimen in 740 Adults (predominantly Women) in West Africa

Summary: In sub-Saharan Africa, the position of efavirenz as a first-line nonnucleoside reverse transcriptase inhibitor remains to be discussed. We report here the 6-month efficacy and tolerance of an efavirenz-containing highly active antiretroviral therapy in a large cohort of HIV-1-infected adults. Seven hundred forty highly active antiretroviral therapy-naive adults (74% women; 14% with positive serum HBs antigen and 21% with abnormal baseline transaminase value) started zidovudine + lamivudine + efavirenz. At month 6, 1.2% of them were dead, 87% had undetectable viral load, and 7% had abnormal transaminase value. From months 1 to 6, the percentage of women who were actually using a contraceptive method increased from 58% to 80% (65% intramuscular progesterone and 35% oral estrogen/progesterone combination). The incidence of pregnancy was 2.6/100 woman-years (95% confidence interval, 0.67-4.51), and 86% of pregnant women voluntarily interrupted the pregnancy with no intervention on our part. Before month 6, only 0.8% of patients permanently discontinued efavirenz for severe adverse effects (neurologic, 0.6%; cutaneous, 0.1%; and hepatic, 0.1%). The leading cause of severe morbidity was tuberculosis. Considering the very high hepatic and cutaneous tolerance, efavirenz could be considered as a valuable first-line drug for women of childbearing age who agree to use contraception in sub-Saharan Africa, provided that the risk of teratogenicity should be closely monitored.

Comparison of the Generic HIV Viral Load assay with the Amplicor HIV-1 monitor v1.5 and Nuclisens HIV-1 EasyQ v1.2 techniques for plasma HIV-1 RNA quantitation of non-B subtypes: the Kesho Bora preparatory study

The implementation of cost effective HIV-1 RNA quantitation assays in resource-poor settings is of paramount importance for monitoring HV-1 infection. A study comparing the analytical performance of three HIV-1 RNA assays (Generic HIV Viral Load, Amplicor v1.5 and Nuclisens EasyQ v1.2) was performed on 160 plasma samples from 160 consecutive antiretroviral treatment naive HIV-1-infected pregnant women assessed for eligibility in the Kesho Bora trial aimed at prevention of mother-to-child transmission of HIV-1 in three African countries (Burkina Faso, Kenya and South Africa). Correlation and agreement of results of the three assays were assessed for plasma HIV-1 RNA quantitation in specimens harbouring mainly sub-subtype A1, subtype C, and circulating recombinant form (CRF) 02_AG and CRF06_cpx. Good degrees of correlation and agreement were observed between these HIV-1 RNA assays. However, nine (9/160, 5.6%) strains detectable with the Generic HIV Viral Load assay were not detected by either the Amplicor (n=7) or EasyQ (n=2) test. One strain (0.6%) was missed with the Generic HIV Viral Load assay. Further, concordantly positive plasma samples harbouring CRF02_AG and CRF06_cpx yielded significantly higher HIV-1 RNA concentrations when tested by Generic HIV Viral Load, as compared to Amplicor v1.5 (mean differences, +0.33 and +0.67 log(10) copies/ml; P=0.0004 and P=0.002, respectively). The Generic HIV Viral Load assay accurately quantified the majority of the non-B HIV-1 subtypes assessed in this study. Due to its low cost (approximately 10 US

Dried blood spot HIV-1 RNA quantification using open real-time systems in South Africa and Burkina Faso.

/test), this assay performed with open real-time PCR instruments is now used routinely in the Kesho Bora trial and may be recommended in other African settings.