Risk of virological failure and drug resistance during first and second-line antiretroviral therapy in a 10-year cohort in Senegal: results from the ANRS 1215 cohort.

BACKGROUND: In 1998, Senegal launched one of Africa's first antiretroviral therapy (ART) programs. Since then, the number of treated patients in Africa has substantially increased thanks to simplification in treatment management. Although good outcomes over the first years of ART have been observed in sub-Saharan Africa, little is known about the long-term (>5 years) risks of virological failure and drug resistance and about second-line treatment response. METHODS: Patients from the ANRS-1215 cohort in Senegal, started with either one nonnucleoside reverse transcriptase inhibitor or indinavir, a first-generation nonboosted protease inhibitor, followed for >6 months and having >1 viral load (VL) measurement were included. Virological failure was defined as 2 consecutive VL measurements >1000 copies/mL. RESULTS: Of the 366 patients included, 89% achieved a VL <500 copies/mL. The risk of virological failure at 12, 24, and 60 months was 5%, 16%, and 25%, being higher in younger patients (P = 0.05), those receiving a protease inhibitor-containing regimen (P = 0.05), and those with lower adherence (P = 0.03). The risk of resistance to any drug at 12, 24, and 60 months was 3%, 11%, and 18%. After virological failure, 60% of the patients were switched to second-line treatments. Although 81% of the patients achieved virological success, the risk of virological failure was 27% at 24 months, mostly in patients with multiple resistances. CONCLUSIONS: In this cohort, virological outcomes for first-line treatments were good compared with those from high-resource settings. However, the rate of virological failure for second-line treatment was high, probably because of accumulation of resistances.

Sensitivity of IFN-gamma release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progression.

BACKGROUND: Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV. OBJECTIVE: To assess the validity of a newly developed in-house ELISPOT interferon-gamma release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST). METHODOLOGY/PRINCIPAL FINDINGS: ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain. CONCLUSION: Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.