Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals.

OBJECTIVE: To assess outcomes after antiretroviral therapy (ART) in adolescents and youth in Haiti, a country with a generalized epidemic of infection with HIV-1. METHODS: An assessment was made of survival, plasma HIV-1 ribonucleic acid (RNA) concentrations and HIV-1 drug resistance patterns after 12 months of ART in patients aged 13-25 years who presented to a clinic in Port-au-Prince, Haiti, with AIDS between 1 March 2003 and 31 December 2005. Participants received ART in accordance with WHO guidelines. Kaplan-Meier analysis was used to estimate survival probabilities and their 95% confidence intervals (CI) for the period from ART initiation to death. FINDINGS: Of a total of 146 patients, 96 (66%) were female; the median CD4+ T-cell count at baseline was 129 cells/ml. By Kaplan-Meier analysis, 13% of the patients had died at 12 months, 17% at 24 months and 20% at 36 months. A plasma HIV-1 RNA concentration > or = 50 copies/ml was seen in 40 (51%) of 79 patients 12 months after treatment initiation and was associated with poor ART adherence. Among 29 patients with > 1000 copies/ml at 12 months, resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 23 cases (79%); to both NNRTIs and lamivudine in 21 (72%) cases; and to NNRTIs, lamivudine and other nucleoside reverse transcriptase inhibitors in 10 (35%) cases. One hundred and six participants (73%) reported sexual intercourse without condoms, and 35 of the 96 women (36%) were pregnant during follow-up. CONCLUSION: Adolescents and youth with AIDS receiving ART are at risk of virologic failure and disease progression and can therefore transmit HIV-1 to sexual partners and infants. Strategies to target the special needs of this age group are urgently needed.

Serologic imprint of dengue virus in urban Haiti: characterization of humoral immunity to dengue in infants and young children.

Dengue is endemic to Haiti but not recognized as an important illness in the autochthonous population. To evaluate the prevalence of antibodies to dengue virus (DENV), serum samples from infants and young children 7-36 months of age (n = 166) were assayed by plaque reduction neutralization assays to each DENV serotype. Dengue virus serotype 1 had infected 40% of this study population, followed by serotype 2 (12%), serotype 3 (11%), and serotype 4 (2%). Fifty-three percent of infants and young children less than 12 months of age had already experienced DENV infection, and the seroprevalence of antibody to DENV increased to 65% by 36 months. Heterotypic antibody responses were an important component of the total dengue immunity profile.

AIDS diarrhea and antiretroviral drug concentrations: a matched-pair cohort study in Port au Prince, Haiti.

Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea.

CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti.

BACKGROUND: Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince. METHODS: An observational study characterized relationships between clinical factors, pharmacokinetics, and treatment response among antiretroviral-naive patients initiating once-daily treatment with efavirenz plus twice-daily treatment with zidovudine and lamivudine. Plasma drug concentrations were determined at weeks 2 and 4. Drug doses were directly observed by field workers or designated family members. We retrospectively characterized relationships between efavirenz concentrations and 50 single-nucleotide polymorphisms in CYP2B6 and several polymorphisms in CYP2A6, CYP3A4, CYP3A5, and ABCB1. RESULTS: Plasma specimens for efavirenz analysis were obtained from study participants a mean (+/- standard deviation) of 13.9 +/- 1.6 h after they received the dose. As expected, CYP2B6 516G-->T was associated with increased plasma efavirenz concentrations (Spearman rho = 0.71; P < .001), as were 10 polymorphisms in linkage disequilibrium with 516G-->T. Distinct CYP2B6 polymorphisms were associated with decreased plasma efavirenz concentrations (greatest absolute rho = 0.48; P = .001). Associations were replicated by results from a recent pharmacokinetic study involving 34 healthy, human immunodeficiency virus-negative African Americans. CONCLUSIONS: Relatively frequent CYP2B6 polymorphisms may predict decreased plasma efavirenz exposure in patients of African descent. If replicated in other cohorts, the implications of these novel associations for treatment response warrant further study.

Potential of a simplified p24 assay for early diagnosis of infant human immunodeficiency virus type 1 infection in Haiti.

With global efforts to scale up the prevention of mother-to-child transmission services and pediatric antiretroviral therapy, there is an urgent need to introduce a simple, low-cost infant human immunodeficiency virus test in the field. We postulated that the p24 antigen capture enzyme-linked immunosorbent assay could be simplified by eliminating signal amplification without compromising diagnostic accuracy.