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 >or=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.

Pediatric viral human immunodeficiency virus type 1 RNA levels, timing of infection, and disease progression in African HIV-1-infected children.

OBJECTIVE: To describe plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in African HIV-1-infected children in relation to the timing of infection and disease progression. METHODS: A retrospective cohort study was conducted of 80 children who were born to HIV-1-positive mothers and clinically followed from birth to 18 months of age in the ANRS 049 Ditrame project, Abidjan, Côte d'Ivoire (West Africa). The diagnosis and timing of pediatric HIV-1 infection were determined prospectively according to HIV-1 DNA polymerase chain reaction results. A total of 364 HIV-1 RNA viral load (VL) measurements were assessed retrospectively. Kaplan-Meier analyses and proportional hazards models were used to evaluate the prognostic value of pediatric VL and covariates for HIV disease progression or death. RESULTS: Mean initial positive VL was significantly lower among children who were infected in utero (4.94 log10/mL, n = 12) than in children who were infected later (5.6-6.1 log10/mL, n = 68). In the first 6 months after diagnosis, HIV-1 RNA levels peaked (> or =6 log10/mL), regardless of timing of infection. Then, a slow decline (overall slope, -0.076 log10 copies/mL/mo) was observed until 18 months of age. A 1 log10 higher value of the pediatric peak VL (risk ratio [RR]: 1.85; 95% confidence interval [CI]: 1.0-3.44) and of the maternal VL at delivery (RR: 1.90; CI: 1.16-3.12) were independently associated with an increased risk of rapid progression to acquired immune deficiency syndrome (AIDS) or death at 18 months of life (23 AIDS diagnoses and 31 deaths). Disease progression or death was more rapid for girls than for boys (RR: 2.26; CI: 1.39-4.96). CONCLUSIONS: In Africa, pediatric HIV-1 RNA levels are very close to those described in industrialized countries and seem to be predictive of AIDS stage or death, as in industrialized countries. With antiretroviral therapy becoming more widely available, the early identification and monitoring of pediatric HIV disease remains of paramount importance in Africa.

Primary HIV-1 infection in African children infected through breastfeeding.

OBJECTIVES: To describe acute retroviral syndrome and associated primary viraemia in African children infected with HIV-1 through breastfeeding. DESIGN: Matched case-control study performed retrospectively within the ANRS 049 DITRAME project conducted in 1995-1998 in Abidjan, Côte d'Ivoire. METHODS: Cases were children infected by HIV-1 postnatally through breastfeeding. All were HIV-1 negative by DNA PCR at least 45 days of age, but positive on a subsequent sample. This period was considered as surrounding the estimated date of postnatal contamination. Signs/symptoms occurring within this period were recorded in cases and compared with those occurring during the same time period in uninfected breastfed children (controls). For cases, plasma specimens were tested for HIV-1 plasma RNA using the branched DNA assay. RESULTS: Of 22 infants infected postnatally (median age at first positive sample, 185 days; range, 87-373 days), 21 (95.5%) exhibited at least one clinical sign, compared with only 27 of the 44 (61.4%) uninfected children (P = 0.003). Three independent factors were associated with primary HIV-1 infection: mononucleosis-like syndrome [odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4-47.8], dermatitis (OR, 6.0; CI, 1.1-31.9), and generalized lymphadenopathy (OR, 26.5; CI, 2.0-348.4). Among cases, initial median plasma HIV-1 RNA viral load was 5.92 log10 copies/ml; this declined to 4.96 log10 12 months after the first positive viral load. CONCLUSIONS: These results may be useful for the recognition of early paediatric cases of postnatal transmission in Africa and could enable targeting of those who should benefit from HIV RNA or DNA testing for primary HIV-1 infection and their subsequent care.

Field acceptability and effectiveness of the routine utilization of zidovudine to reduce mother-to-child transmission of HIV-1 in West Africa.

OBJECTIVE: To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission (MTCT) of HIV in breastfed children after a randomized clinical trial demonstrated its efficacy in Côte d'Ivoire and Burkina Faso. METHODS: Pregnant women aged 18 years or older, who had confirmed HIV-1 infection, haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36-38 weeks' gestation to receive an oral short course of zidovudine. Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction, or if aged 15 months or older, a positive HIV serology. RESULTS: The acceptability of HIV pretest counselling was significantly higher in the cohort (90.3%) than in the trial (83.7%) (P < 0.001), but the return rate for HIV test results and for inclusion was low. A similar proportion of women accepted starting zidovudine in the cohort, 30.4% compared with 27.3% in the trial (P = 0.13). The proportions of women who took more than 80% of the expected zidovudine regimen were 81.8% before labour, 86.7% during labour, and 88.1% during the postpartum period, compared with those observed during the trial, 78.1, 81.1, and 85%, respectively. The MTCT probability at age 15 months was 19.6% in the cohort (n = 185) versus 21.2% in the trial (P = 0.52). CONCLUSION: The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures. For women who consent, zidovudine is well accepted and efficacious under routine circumstances.