Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BACKGROUND: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. METHODS: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. RESULTS: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. CONCLUSIONS: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.

Increasing rate of TAMs and etravirine resistance in HIV-1-infected adults between 12 and 24 months of treatment: the VOLTART cohort study in Côte d'Ivoire, West Africa.

BACKGROUND: In sub-Saharan Africa, most HIV-infected patients receive antiretroviral therapy (ART) without virological monitoring. Longitudinal data on secondary resistance are rare. METHODS: We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had plasma HIV-1 RNA viral load (VL) tests at months 12 (M12) and 24 (M24) after ART initiation and HIV-1 resistance genotype tests if VL was detectable (≥300 copies/mL). RESULTS: Overall, 1573 patients initiated ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M12 and M24, 944 and 844 patients, respectively, remained in active follow-up. Among them, 25% (M12) and 27% (M24) had detectable VLs and 12% (M12) and 19% (M24) had virus resistant to at least 1 antiretroviral drug, accounting for 54% (M12) and 75% (M24) of patients with detectable VLs. Among the resistant strains, 95% (M12) and 97% (M24) were resistant to lamivudine/emtricitabine, efavirenz, and/or nevirapine, the frequency of thymidine analog mutations increased from 8.1% (M12) to 14.7% (M24) and etravirine resistance increased from 13.5% (M12) to 24.5% (M24). CONCLUSIONS: Of the patients with detectable VLs at M24, 25% still did not harbor resistant virus. Preventing mutations from emerging with adherence reinforcement in patients with detectable VLs remains important beyond M24. Switching therapy early in patients with resistance to 3 TC/FTC and/or to nonnucleoside reverse transcriptase inhibitors to prevent extended resistance to nucleoside reverse transcriptase inhibitors and etravirine resistance from occurring is also a major challenge.

Medication possession ratio: predicting and decreasing loss to follow-up in antiretroviral treatment programs in Côte d'Ivoire.

BACKGROUND: In antiretroviral therapy (ART) programs, decreasing loss to follow up (LTFU) is a major priority. METHODS: We conducted a prospective study in Abidjan. Adults who started ART between June 2005 and May 2008 and were still in care 6 months later had monthly visits, biannual CD4 counts, computerized data collection and home visits (routine follow-up). A subset of patients also had biannual plasma HIV-1 RNA measurements, with a physician and a research assistant hired to pay particular attention to their visits (enhanced follow-up). We analyzed the association between 18-month outcomes and pre-ART characteristics, medication possession ratio (MPR) and type of follow-up. Patients were LTFU if their last visit was before month-18 and they had not returned to care by month-24. RESULTS: 2,074 patients started ART, of whom 1,636 (79%) were still in care at month-6. The routine (n = 999) and enhanced (n = 637) groups had similar baseline characteristics. From month-6 to month-18, they had similar death rates (routine 3.6%, enhanced 3.9%, P = 0.74), but the enhanced group had significantly less LTFU (routine 11.3%, enhanced 5.8%, P < 0.001). In multivariate analysis, the risk of LTFU from month-6 to month-18 was 46% lower with enhanced follow-up, 56% higher in patients living outside the centre area, and 4.0 fold higher in patients with a low MPR (<80%) between ART initiation and month-6. CONCLUSIONS: In patients still in care at 6 months, a low MPR in the first 6 months was strongly associated with further LTFU. Simple follow-up enhancement halved the LTFU rate in the following year.

Association between medication possession ratio, virologic failure and drug resistance in HIV-1-infected adults on antiretroviral therapy in Côte d'Ivoire.

BACKGROUND: Adherence is a strong determinant of viral suppression with antiretroviral therapy (ART) but measuring it is challenging. Medication delivery can be measured accurately in settings with computerized prescription databases. We studied the association between medication possession ratio (MPR), virologic suppression, and resistance to ART in Côte d'Ivoire. METHODS: We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had viral load (VL) tests at month 6 (M6) and month 12 (M12) after ART initiation and genotype tests if VL was detectable (≥300 copies/mL). MPR was defined as the number of daily doses of antiretroviral drug actually provided divided by the total number of follow-up days since ART initiation. RESULTS: Overall, 1573 patients started ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12, 996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients had detectable VL, including 7% (M6) and 11% (M12) with ≥1 resistance mutation. Among patients with MPR of ≥95%, 80%-94%, 65%-79%, 50%-64%, and <50% at M12, the proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67% [31%], and 85% [37%]. Among patients with ≥1 mutation at M12, 86% were resistant to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs. CONCLUSIONS: MPR was strongly associated with virologic outcomes. Half of those with detectable VL at M12 had no resistance mutations. MPR should be used at M6 to identify patients who might benefit from early interventions to reinforce adherence.