A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Clonality of Mycobacterium ulcerans by Using VNTR-MIRU Typing in Ivory Coast (Côte d'Ivoire), West Africa

International audienceBuruli ulcer (BU) is neglected skin disease caused by Mycobacterium ulcerans. The lack of early diagnosis and treatment causes severe disability. In Central and in West Africa, BU is endemic and its control is difficult because the most cases occur in rural regions. The molecular particularity of M. ulcerans was the acquisition of the virulence plasmid pMUM001. Genetic analyses have demonstrated the high diversity with variable number tandem repeats (VNTR) and Mycobacterial Interspersed Repetitive Units (MIRU) in M. ulcerans and in mycolactone producing Mycobacteria (MPMs). Objective: The objective of this study was to investigate the molecular diversity by using MIRU-VNTR method in clinical samples of BU patients in Côte d'Ivoire. Study Design: 21 clinical samples were collected from BU patients in different sites and were first analyzed in molecular diagnosis of BU using two targets insertion sequence IS2404 and keto reductase-B-domain (KR). In a second step, we have analyzed the strains by PCR typing for four specific and sensitive markers MIRU1, VNTR6, ST-1 and VNTR19. Results and Conclusion: 100% of clinical samples were positive in molecular tests for IS2404 and 95% for KR and confirm M. ulcerans in the samples. By PCR typing, we have found 61.9 % positive for MIRU1 and 52%, 85.7%, and 61.9% for VNTR6, ST-1 and VNTR19 respectively. One of sample was negative for all genotyping markers. Two different genetic profiles were identified by MIRU1 and ST-1 loci by gel-analyzed of the amplified products. The VNTR profile C (3,1,1) corresponding of 3 copies MIRU1, 1 copy VNTR6 and 1 copy ST-1 was detected in 28.5% of samples and confirms the West African genotype in Côte d'Ivoire. Different genetic strains of M. ulcerans were co-circulated in the same endemic region in the country. This study has described first the circulating of different genetic strains of M. ulcerans in Côte d'Ivoire

Susceptibilities to co-trimoxazole of pathogens isolated from blood and stool specimens in Abidjan, Ivory Coast, 1994 to 1996.

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