prophylaxis has no impact on incidence or detection of tuberculosis (TB) in people with HIV, a study published PLoS
One shows. The prospective, observational study involved 2393 adult participants
in Soweto, South Africa. All had a CD4 cell count below 350 cells/mm3.
Participants taking cotrimoxazole prophylaxis actually had a higher risk of TB
compared to participants not taking the treatment. But the authors believe this was
due to residual confounding. Prophylaxis with the drug did not compromise TB
diagnosis and had a protective effect in term of overall mortality.
neither a protective effect on TB incidence nor an apparent effect on the
diagnosis of TB among HIV-infected patients receiving cotrimoxazole,” write the
authors. “Unexpectedly, we found that the risk of TB disease appeared to be
increased among individuals receiving cotrimoxazole. Although this result
persisted after adjusting for CD4 count and WHO clinical stage, we believe that
this was a result of residual confounding, a hypothesis supported by the loss
of association when we restricted our analysis to culture confirmed TB.”
TB is the single
biggest cause of death among HIV-positive people in Africa. Cotrimoxazole
prophylaxis is protective against a number of bacterial infections and is
recommended for people with low CD4 cell counts. Its impact on the risk of TB
is uncertain, but laboratory studies suggest that the drug may possess anti-TB
activity. However, there are concerns that any anti-mycobacterial activity may
complicate the diagnosis of culture-confirmed TB.
Because of these
unanswered questions and concerns, an international team of investigators
designed a study assessing TB incidence and culture characteristics according to the
use of cotrimoxazole prophylaxis.
The study was
conducted between 2003 and 2009. Participants had a median age at baseline of
33 years and 29% had WHO stage 3 or 4 disease. Median CD4 cell count on entry
to the study was 209 cells/mm3. Three-quarters of the participants were
prescribed to 1294 participants (54%) for a total of 688 person-years. The median
CD4 cell count when initiating this therapy was 162 cells/mm3.
contributed 4875 person-years of follow-up. During this time, 179 patients
(7.5%) were diagnosed with incident TB. The overall incidence was 3.7 per 100
person-years. However, incidence was significantly higher among people taking
cotrimoxazole compared to those not taking this prophylaxis (7.6 vs. 3.6 per
100 person-years, p < 0.01).
analysis, the factors associated with an increased risk of incident TB were
male sex, lower body mass index (BMI), more advanced HIV disease at baseline,
lower CD4 cell count, not taking antiretroviral therapy, and cotrimoxazole
prophylaxis (HR = 1.7; 95%, 1.22-2.2).
The final finding
surprised the investigators. They therefore repeated their analysis, this time
limited to the 655 participants who had laboratory TB investigations, including the
52 individuals with culture-confirmed TB. No association was found between
incident TB and use of cotrimoxazole (HR = 0.97; 95% CI, 0.39-0.42).
cotrimoxazole prophylaxis did not complicate the laboratory diagnosis of TB.
Similar proportions of TB cultures were positive for participants taking the drug
and not taking the drug (8 vs 10%). The median time to positive culture was
18 days and 20 days, respectively, for people taking and not taking
A total of 125
participants died during follow-up. After controlling for confounders,
cotrimoxazole prophylaxis was shown to reduce the risk of mortality by 52% (HR
= 0.48; 95% CI, 0.21-1.1).
a vital part of the HIV care package with well documented improvements in
survival,” conclude the authors. “However, cotrimoxazole prophylaxis does not
appear to effect either TB disease incidence or detection.”