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Should cotrimoxazole prophylaxis be taken by all adults with HIV in Africa?

Mermin, Jonathana; Lule, John Ra; Ekwaru, John Pa; Pitter, Christiana,b

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aCDC Uganda, Global AIDS Program, Centers for Disease Control and Prevention, Uganda Virus Research Institute, Entebbe, Uganda

bUniversity of California, San Francisco, CA, USA.

Grimwade et al. [1] presented convincing information regarding the effectiveness of cotrimoxazole prophylaxis in preventing mortality among patients with tuberculosis in South Africa, even without testing for HIV. Another recent trial [2] presented data regarding the efficacy of cotrimoxazole prophylaxis among children with HIV infection in Zambia regardless of the CD4 cell count or age. As a result of that study, the World Health Organization (WHO) and the Joint UN programme on HIV/AIDS (UNAIDS) developed interim guidelines that recommend prophylaxis for all symptomatic children with HIV infection, eliminating previous criteria using CD4 cell percentages [3].

Should cotrimoxazole prophylaxis recommendations be expanded to include all adults with HIV? WHO/UNAIDS guidelines currently recommend cotrimoxazole prophylaxis only for adults with CD4 cell counts of less than 500 cells/μl or WHO stage 2, 3, or 4 disease [4]. However, a study of cotrimoxazole prophylaxis in Côte d’Ivoire [5] showed improvements in event-free survival even among individuals with CD4 cell counts greater than 500 cells/μl. In a cohort study in Uganda [6], which included 482 adults with HIV, 36% with CD4 cell counts greater than 500 cells/μl, we previously reported that the incidence of diarrhea, malaria, hospitalizations, and death were 30–70% lower during the time of cotrimoxazole prophylaxis than before. The morbidity and mortality effects were similar across all CD4 cell count strata, and statistically significant reductions in diarrhea and malaria were observed even among individuals with CD4 cell counts greater than 500 cells/μl.

To examine further the potential effects of cotrimoxazole prophylaxis for individuals with high CD4 cell counts, we conducted a subanalysis adjusting for the baseline CD4 cell count, sex, and age, of 78 adults from our cohort with baseline CD4 cell counts greater than 500 cells/μl who survived the entire study. The annual rate of decline in CD4 cell count was less during prophylaxis than before [mean difference in absolute rate 230 cells/μl per year, 95% confidence interval (CI) 33–427 cells/μl, P = 0.022; mean difference in percentage change 29% per year, 95% CI 4–55%, P = 0.023).

This information might have broader relevance. The initial studies regarding the efficacy of cotrimoxazole prophylaxis were conducted in industrialized countries and focused on preventing Pneumocystis jiroveci pneumonia, and consequently included only individuals with CD4 cell counts less than 200 cells/μl. Subsequent studies also showed reductions in bacterial pneumonia, toxoplasmosis, and other opportunistic illnesses. Studies of the effect of cotrimoxazole prophylaxis on a variety of opportunistic illnesses among individuals with higher CD4 cell counts outside of Africa might be useful.

The benefits of cotrimoxazole prophylaxis in reducing morbidity and mortality among adults with CD4 cell counts greater than 500 cells/μl, its minimal cost, the potential benefit in delaying the progression of HIV disease by reducing the rate of CD4 cell count decline, the low risk of serious adverse effects, and the simplicity of a parsimonious approach, would make changing guidelines to include all adults with HIV infection in Africa worthwhile.

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References

1. Grimwade K, Sturm AW, Nunn AJ, Mbatha D, Zungu D, Gilks CF. Effectiveness of cotrimoxazole prophylaxis on mortality in adults with tuberculosis in rural South Africa. AIDS 2005; 19:163–168.

2. Chintu C, Bhat GJ, Walker AS, Mulenga V, Sinyinza F, Lishimpi K, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet 2004; 364:1865–1871.

3. WHO/UNAIDS/UNICEF. Joint WHO/UNAIDS/UNICEF statement on use of cotrimoxazole as prophylaxis in HIV exposed and HIV infected children. Available at: http://www.who.int/3by5/mediacentre/news32/en/. Accessed: 28 February 2005.

4. WHO and UNAIDS. Provisional WHO/UNAIDS Secretariat recommendations on the use of cotrimoxazole prophylaxis in adults and children living with HIV/AIDS in Africa, 2000. Geneva: World Health Organization; 2000. Available at: http://www.unaids.org/EN/other/functionalities/Search.asp. Accessed: 28 February 2005.

5. Anglaret X, Chêne G, Attia A, Toure S, Lafont S, Combe P, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d’Ivoire: a randomised trial. Lancet 1999; 353:1463–1468.

6. Mermin J, Lule J, Ekwaru JP, Malamba S, Downing R, Ransom R, et al. Effect of cotrimoxazole prophylaxis on morbidity, mortality, CD4 cell count, and HIV viral load among persons with HIV in rural Uganda. Lancet 2004; 364:1428–1434.

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© 2005 Lippincott Williams & Wilkins, Inc.

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