Effect of cotrimoxazole on causes of death, hospital admissions and antibiotic use in HIV-infected children.
BACKGROUND
Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.


METHODS
CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups.


RESULTS
Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)].


CONCLUSIONS
Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.
Mulenga
Veronica
V
University Teaching Hospital, Lusaka, Zambia.
Ford
Deborah
D
Walker
A Sarah
AS
Mwenya
Darlington
D
Mwansa
James
J
Sinyinza
Frederick
F
Lishimpi
Kennedy
K
Nunn
Andrew
A
Gillespie
Stephen
S
Zumla
Ali
A
Chintu
Chifumbe
C
Gibb
Diana M
DM
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D024881:Drug Resistance, Bacterial; D004653:Empyema / Q000401:mortality / Q000821:virology; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007223:Infant; D011014:Pneumonia / Q000401:mortality / Q000821:virology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D015024:Zambia
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination