prophylaxis, while safe and well-tolerated, had no significant effect on
reducing death or hospital admissions among HIV-infected women followed for one
year after having given birth in Zambia, according to Andrew J Nunn and
colleagues in a randomised, placebo-controlled trial (TOPAZ) reported in the advance
online edition of Tropical Medicine and
loss to follow-up was significant (40%), the authors noted a possible benefit
to breast-fed babies of women who received cotrimoxazole.
rates, before the infants got open-label cotrimoxazole, were 19.5 (95% CI:
12.9 to 29.3) per 100 child-years in the cotrimoxazole arm, compared to 34.5
(95%CI: 24.4 to 48.8) per 100 child-years in the placebo arm, P=0.1.
and other opportunistic infections (OIs) continue to account for the high death
and disease rate in people with HIV in resource-poor settings where access to
antiretroviral therapy remains out of reach for many. HIV is the leading cause
of death and disease among women of reproductive age in sub-Saharan Africa. In Zambia, HIV prevalence among pregnant women is
reported to be as high as 34%, note the authors.
attention has been paid to the prevention of opportunistic infections in
HIV-infected pregnant women either before or after birth, they add.
ART availability in African countries, and based on the evidence of its efficacy
as an effective prophylaxis against bacterial and other opportunistic
infections, the World Health Organization (WHO) and UNAIDS in 2000 made a
provisional recommendation that cotrimoxazole be given to all adults and
children in Africa with symptomatic HIV-1
infection. (Cotrimoxazole prophylaxis is now both widely available and its
value in preventing opportunistic infections recognised.)
careful consideration and review of the existing evidence, the Zambian Ministry
– together with the University
of Zambia Research and
– agreed to undertake three randomised, placebo-controlled
trials looking at cotrimoxazole prophylaxis in HIV infection in children, in
adults with tuberculosis and in women after childbirth. The first two showed a
significant reduction of all causes of death in those getting cotrimoxazole.
on the findings from the third trial, the authors note this is the only
double-blind, placebo-controlled randomised trial of cotrimoxazole prophylaxis that
has been undertaken in HIV-infected women after childbirth in Africa.
September 2000 to August 2003, 600 postnatal women with HIV at WHO stage 2 or 3
were randomised to receive cotrimoxazole or matching placebo for a year.
Follow-up closed in September 2004 when funding became available for those
eligible for ARVs to go on to treatment. Primary outcomes were death from any cause, hospital
admission and serious adverse events.
data was available for 60% (355: 180 on cotrimoxazole and 175 on placebo).
women (17 on cotrimoxazole and 19 on placebo) died and an additional 11 (5 on
cotrimoxazole and 6 on placebo) were admitted to hospital.
was no significant difference in the combined event rates between the two
treatment arms with 9.4 per 100 women-years in the cotrimoxazole arm (95% CI:
6.2 to 14.3) and 11.4 per 100 women-years in the placebo arm (95% CI: 7.7-16.9):
unadjusted HR-0.82, 95% CI: 0.46 to 1.45, P=0.49.
authors suggest that the relatively small number of deaths is because the women
were at an early stage of HIV infection. They add that, in contrast to other
studies, there was no measurable mortality benefit for women in the
cotrimoxazole arm. They suggest another possibility: “cotrimoxazole prophylaxis
for the prevention of HIV-associated OIs selects for resistant pathogens as
shown in a study of Kenyan adults.”
high loss to follow-up (40%) could also explain the lack of effect of
cotrimoxazole as well as the lower than anticipated event rate in the placebo
group, the authors note. They suggest, in contrast to other studies with good
follow-up, this may be because this cohort were not yet immunosuppressed, felt
well and did not see the need to attend clinics.
authors suggest that social pressures may have also played a role. They add
that provision of food and refund of transport monies had no effect on follow-up.
authors note most African countries do not have the resources to provide ART to
all. So the critical need for standardised, evidence-based recommendations on
preventive measures remains. The development of an overall package of care is
in process, they add.
to WHO, there is clear evidence of the benefits of prophylaxis for both
cotrimoxazole and isoniazid preventive therapy, notably in areas where HIV and
TB are endemic, yet implementation is a problem.
authors conclude: ”provision of adequate care through infection-prevention
regimens for the large numbers of people affected by HIV remains a daunting