Antiretroviral treatment changes in adults from Côte d'Ivoire: the roles of tuberculosis and pregnancy.

OBJECTIVE: To determine the rates and causes of first antiretroviral treatment changes in HIV-infected adults in Côte d'Ivoire. METHODS: We evaluated adults who initiated antiretroviral treatment in an outpatient clinic in Abidjan. We recorded baseline and follow-up data, including drug prescriptions and reasons for changing to alternative first-line regimens (drug substitution for any reason but failure) or second-line regimens (switch for failure). RESULTS: Two thousand and twelve HIV-infected adults (73% women) initiated antiretroviral treatment. At baseline, 9% of all patients were on treatment for tuberculosis and 3% of women were pregnant. First-line antiretroviral treatment consisted of two nucleoside reverse transcriptase inhibitors (58% stavudine-lamivudine, 42% zidovudine-lamivudine) and efavirenz (63%), nevirapine (32%) or indinavir (5%). Median follow-up time was 16.9 months. During this time, 205 (10%) patients died and 261 (13%) were lost to follow-up. Overall, the rate of treatment modifications was 20.7/100 patient-years. The most common modifications were drug substitutions for intolerance (12.4/100 patient-years), pregnancy (4.5/100 patient-years) and tuberculosis (2.5/100 patient-years). The rates of intolerance-related substitutions were 17.9/100 patient-years for stavudine, 6.3/100 patient-years for nevirapine, 3.9/100 patient-years for zidovudine and 0.1/100 patient-years for efavirenz. Twenty percent of efavirenz substitutions resulted from pregnancy and 18% of nevirapine substitutions were related to tuberculosis treatment. CONCLUSION: During the first months following antiretroviral treatment initiation, a third of all treatment changes occurred for reasons other than intolerance to the drug or treatment failure. In Africa, drug forecasting is crucial to ensuring the success of HIV treatment programmes. Drugs that do not require interruptions during pregnancy or tuberculosis treatment should be made more readily available as first-line drugs in sub-Saharan Africa.

HIV-1 DNA in peripheral blood mononuclear cells is strongly associated with HIV-1 disease progression in recently infected West African adults.

OBJECTIVE: To analyze the association between the HIV-1 DNA level in peripheral blood mononuclear cells (PBMCs) and disease progression in recently infected West African adults. METHODS: HIV-1 DNA levels were measured in the PBMCs of 200 adults in the French National Agency for Research on AIDS and viral Hepatitis (ANRS) 1220 cohort who had recently been infected with HIV-1. The association between baseline HIV-1 DNA levels and disease progression was analyzed using multivariate Cox regression. Disease progression was defined as the occurrence of any of the following outcomes: death, first World Health Organization stage 3-4 event, or CD4 count<200/mm. RESULTS: About 200 participants were followed for a median of 30 months. At baseline, the median time from HIV-1 seroconversion was 9 months, median CD4 T-cell count was 471/mm, median HIV-1 DNA level was 3.0 log10 copies/10 PBMCs, and median plasma HIV-1 RNA level was 4.6 log10 copies/mL. The 5-year probability of remaining free of any outcome was 0.74 [95% confidence interval (CI): 0.61 to 0.83] and 0.36 (95% CI: 0.23 to 0.49) in patients with baseline HIV-1 DNA3.0 log10 copies/10 PBMCs, respectively (P<0.001). The adjusted hazard ratio of disease progression was 2.17 in patients with HIV-1 DNA>3.0 log10 copies/10 PBMCs compared with other patients (95% CI: 1.24 to 3.80, P=0.007). The only other factor associated with progression was follow-up CD4 count (hazard ratio=1.23 per 100 cells/mm decrease; 95% CI: 1.07 to 1.41, P=0.003). DISCUSSION: PBMC HIV-1 DNA level was strongly associated with HIV-1 disease progression, even after adjusting for HIV-1 RNA and CD4 T-cell count. Further studies should assess whether patients with high HIV-1 DNA levels should start antiretroviral therapy earlier than other patients.

Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d'Ivoire: 2-year outcomes and determinants.

OBJECTIVE: To assess the rates and determinants of mortality, loss to follow-up and immunological failure in a nongovernmental organization-implemented program of access to antiretroviral treatment in Côte d'Ivoire. METHODS: In each new treatment center, professionals were trained in HIV care, and a computerized data system was implemented. Individual patient and program level determinants of survival, loss to follow-up and immunological failure were assessed by multivariate analysis. RESULTS: Between May 2004 and February 2007, 10,211 patients started antiretroviral treatment in 19 clinics (median preantiretroviral treatment CD4 cell count, 123 cells/microl; initial regimen zidovudine-lamivudine-efavirenz, 20%; stavudine-lamivudine-efavirenz, 22%; stavudine-lamivudine-nevirapine, 52%). At 18 months on antiretroviral treatment, the median gain in CD4 cell count was +202 cells/microl, the probability of death was 0.15 and the probability of being loss to follow-up was 0.21. In addition to the commonly reported determinants of impaired outcomes (low CD4 cell count, low BMI, low hemoglobin, advanced clinical stage, old age and poor adherence), two factors were also shown to independently jeopardize prognosis: male sex (men vs. women: hazard ratio = 1.52 for death, 1.27 for loss to follow-up, 1.31 for immunological failure); and attending a recently opened clinic (inexperienced vs. experienced centers: hazard ratio = 1.40 for death, 1.58 for loss to follow-up). None of the three outcomes was associated with the drug regimen. DISCUSSION: In this rapidly scaling-up program, survival and immune reconstitution were good; women and patients followed up in centers with longer experience had better outcomes; outcomes were similar in zidovudine/stavudine-based regimens and in efavirenz/nevirapine-based regimens. Decreasing the rate of loss to follow-up should now be the top priority in antiretroviral treatment rollout.

Progression to WHO criteria for antiretroviral therapy in a 7-year cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire.

OBJECTIVE: To estimate the probability of reaching the criteria for starting highly active antiretroviral therapy (HAART) in a prospective cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire. METHODS: We recruited participants from HIV-positive donors at the blood bank of Abidjan for whom the delay since the estimated date of seroconversion (midpoint between last negative and first positive HIV-1 test) was < 36 months. Participants were offered early trimethoprim-sulfamethoxazole (cotrimoxazole) prophylaxis, twice-yearly measurement of CD4 count and we made standardized records of morbidity. We used the Kaplan-Meier method to estimate the probability of reaching the criteria for starting HAART according to WHO 2006 guidelines. FINDINGS: 217 adults (77 women (35%)) were followed up during 668 person-years (PY). The most frequent diseases recorded were mild bacterial diseases (6.0 per 100 PY), malaria (3.6/100 PY), herpes zoster (3.4/100 PY), severe bacterial diseases (3.1/100 PY) and tuberculosis (2.1/100 PY). The probability of reaching the WHO 2006 criteria for HAART initiation was estimated at 0.09, 0.16, 0.24, 0.36 and 0.44 at 1, 2, 3, 4 and 5 years, respectively. CONCLUSION: Our data underline the incidence of the early HIV morbidity in an Ivorian adult population and provide support for HIV testing to be made more readily available and for early follow-up of HIV-infected adults in West Africa.