Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.
OBJECTIVE
To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.


METHODS
Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.


METHODS
Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.


RESULTS
Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).


CONCLUSIONS
Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.
INSERM U88, Paris, France. m.maynart@st-maurice.inserm.fr
M
M
Maynart
L
L
Lièvre
P S
PS
Sow
S
S
Kony
N F
NF
Gueye
E
E
Bassène
A
A
Metro
I
I
Ndoye
D S
DS
Ba
J P
JP
Coulaud
D
D
Costagliola
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D015498:HIV-2; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D012675:Senegal; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014505:Urban Population
D000890:Anti-Infective Agents; D004338:Drug Combinations; D010919:Placebos; D015662:Trimethoprim, Sulfamethoxazole Drug Combination