Co-trimoxazole affects survival, CD4 counts, viral load, in HIV-positive Ugandans

Daily co-trimoxazole prophylaxis given to people with HIV in Uganda resulted in signficant reductions in deaths, hospital admissions, malaria and diarrhoea during 18 months of follow-up of a cohort of 509 people with HIV in Uganda, researchers from the United States Centers for Disease Control (CDC) reported in the October 16^th edition of The Lancet.

The study also found that CD4 T-cell declines slowed after people began prophylaxis, and the annual rate of viral load increase was lower.

Co-trimoxazole prophylaxis may prevent the development of a range of opportunistic infections including Pneumocystis pneumonia (PCP), toxoplasmosis and bacterial infections. Although co-trimoxazole prophylaxis has been recommended by the World Health Organization (WHO) for all people with HIV with CD4 cell counts below 500 cells/mm³ in sub-Saharan Africa, few people with HIV receive this treatment. Two randomised placebo-controlled studies of co-trimoxazole prophylaxis in Africa have produced conflicting results: one study in patients with TB and HIV showed benefit (Wiktor 1999), but another study in HIV-positive people found no benefit (Maynart 2001).

One concern about prophylaxis is that high rates of resistance to co-trimoxazole are already present due to malaria treatment. The CDC study was intended to test the effect of co-trimoxazole prophylaxis in a region with a high level of antimicrobial resistance to co-trimoxazole.

The study recruited 509 individuals living with HIV who were clients of The AIDS Support Organisation (TASO) and 1522 HIV-negative household members to serve as a control group to assess background rates of illness in the population.

After five months of follow-up individuals with HIV were offered co-trimoxazole prophylaxis and provided blood for CD4 T-cell counting and malaria testing. Follow-up lasted for 18 months during which time households were visited weekly to record information on the health of study participants.

Seventy four per cent of HIV-positive participants were women, with a median age of 34. The median age of HIV-negative household participants was 10 years.

At baseline 27% of participants had CD4 cell counts below 200 cells/mm³, 37% had counts between 200 and 500 cells/mm³ and 36% had counts above 500 cells/mm³.

Comparing the follow-up period during which co-trimoxazole was taken with the five month observation period, researchers found:

• The death rate was 46% lower during the co-trimoxazole treatment period (p = 0.006). The reduction was significant only for patients with CD4 cell counts below 200 cells/mm³ or WHO stage 3 or 4 disease.
• The rate of malaria was 72% lower during the co-trimoxazole treatment period (p < 0.001) and evidence of malaria parasite infection in the blood fell by 78% (p < 0.001). Malaria was more common in people with HIV.
• Reports of diarrhoea fell by 35% (p < 0.001) during co-trimoxazole treatment despite the fact that 83% of bacterial isolates from stool samples during the co-trimoxazole treatment period were resistant to the drug combination.
• Hospital admissions fell by 15 to 30%.
• Co-trimoxazole was well tolerated. Only one patient had to discontinue treatment permanently and three had mucocutaneous reactions (blistering of the mucous membranes).
• Treatment adherence was high: 90% of patients took at least 75% of their medication according to self-report.
• The mean annual rate of CD4 decline slowed during co-trimoxazole treatment, from 203 to 77 cells/mm³ per annum (p < 0.001).
• The mean annual rate of viral load increase fell from 0.90 to 0.08 log₁₀ per annum.

The authors suggest that viral load and CD4 trends during co-trimoxazole treatment may be a consequence of the effect of prophylaxis on the frequency of opportunistic infections. Viral load tends to rise during acute infections, which in turn may lead to more rapid CD4 cell decline, further weakening the immune system’s response to infections.

“Organisers of HIV programmes should consider providing co-trimoxazole prophylaxis for all people with HIV,” say the authors, “because the numbers needed to treat per life year saved in our study was 2.6 for individuals with CD4 cell counts below 200 and 8.3 for all participants. This low-cost, effective, readily available and relatively non-toxic intervention should become a basic component of HIV/AIDS care throughout Africa.”