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 Abidjan's 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.


RESULTS
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.


CONCLUSIONS
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.
Wiktor
S Z
SZ
Projet RETRO-CI, Abidjan, Côte d'Ivoire. szw0@cdc.gov
Sassan-Morokro
M
M
Grant
A D
AD
Abouya
L
L
Karon
J M
JM
Maurice
C
C
Djomand
G
G
Ackah
A
A
Domoua
K
K
Kadio
A
A
Yapi
A
A
Combe
P
P
Tossou
O
O
Roels
T H
TH
Lackritz
E M
EM
Coulibaly
D
D
De Cock
K M
KM
Coulibaly
I M
IM
Greenberg
A E
AE
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D007560:Cote d'Ivoire / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality; D015497:HIV-1; D015498:HIV-2; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination