Patrice Combe

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial

BACKGROUND There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjans four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.

Objective: To describe the clinical and biologic evolution of HIV‐1 infection in Africa. Methods: One hundred four HIV‐1‐infected individuals were identified prospectively from regular blood donors in Abidjan, Côte d’Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical followup was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. Results: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4+ cell count was 527/mm3 (interquartile range [IR], 395‐684), and the median plasma HIV RNA level was 4.6 log10 copies/ml (IR, 3.8‐4.9). The median follow‐up was 23.9 months, and 95% of the patients received primary prophylaxis with co‐trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B‐defining event. The 3‐year AIDS‐free and symptom‐free probabilities were 96.7% (95% confidence interval [CI], 87.0‐99.2] and 79.3% (95% CI, 67.5‐87.2), respectively. During the first 3 years of follow‐up, we observed that the median plasma viral load stabilized at >4 log10 copies/ml and that the median CD4+ cell count declined by 20 to 25/mm3 per year. Conclusion: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.

Causes and empirical treatment of fever in HIV-infected adult outpatients, Abidjan, Côte d'Ivoire

ObjectivesIn Abidjan, HIV prevalence has been estimated at 20% in outpatients attending community clinics. Documenting causes of fever in HIV-infected adult outpatients may help to improve care in these centres with limited facilities. DesignProspective study. MethodsWe describe all diagnoses and treatments made during febrile episodes in HIV-infected adults participating in the ANRS 059 trial and followed up in a dedicated outpatient centre. ResultsCauses of fever could be identified in half of the 269 febrile episodes. Bacterial diseases were the leading identified cause of fever in all CD4 cell count strata (53, 56 and 43% of identified causes in episodes with CD4 count < 200 × 106/l, 200–499 × 106/l, and ⩾ 500 × 106/l, respectively), followed by malaria (5, 22, and 38%, respectively). Among febrile bacterial diseases, respiratory tract infections and enteritis accounted for 62% of organ involvement, and Streptococcus pneumoniae and non-typhi Salmonella represented 69% of isolated bacterial strains. In these bacterial episodes, an early empirical antibacterial treatment was associated with shorter duration of hospitalization and fever. In the 19 episodes leading to death (7%), the two leading diagnoses were atypical mycobacteriosis (26%) and acute unexplained fever (21%). Death was associated with the absence of antimalarial treatment in the group of acute unexplained fevers. ConclusionsAfrican HIV treatment guidelines should take into account the predominant role of bacterial infections and malaria in HIV-infected adult outpatients. Reports from other African settings would be useful to compare experiences in algorithms of empirical early antibacterial and antimalarial treatments.