The use of prophylaxis, guided by CD4 cell count could significantly cut the incidence of opportunistic infections in HIV-positive individuals in poorer countries, even when antiretroviral therapy is not available, according to a study conducted in South Africa and published in the August edition of the Journal of Acquired Immune Deficiency Syndromes.
There are 25.4 million people living with HIV/AIDS in sub-Saharan Africa. The majority of HIV-positive individuals in this region are not on antiretroviral therapy and remain at risk of life-threatening opportunistic infections. Prophylaxis against opportunistic infections remain the only lifeline for HIV-positive patients without access to potent HIV therapy. However, the critical research and data needed to guide the policy for initiating prophylaxis in HIV-infected African patients lag behind those in the United States and Europe.
CD4 cell count declines have been reported in HIV-infected, HIV treatment-naive US and European patients. This information has informed guidelines for out-patient management of HIV/AIDS patients in these countries.
However, US and European guidelines for the out-patient management of HIV/AIDS patients might not be relevant to African settings. The relationship between CD4 cell counts and the risk for specific opportunistic in HIV-infected Africans also remains unclear. There is an urgent need for guidelines for the timing of prophylaxis against opportunistic infections in African patients. It is against this background that a team of US and South African investigators investigated the relationship between CD4 cell count strata and the incidence of specific infections.
The study took place in two clinics affiliated with the University of Cape Town in South Africa. Although 2,086 patients were enrolled over 16 years, only 1,766 had two or more visits and 974 had two or more CD4 cell count measurements. After 1993, some patients received cotrimoxazole (CTX) prophylaxis; AZT (zidovudine) monotherapy was used infrequently.
Clinical information collected during clinic visits included weight, diagnosis of opportunistic infections and other HIV-related complications, prophylaxis, and medications. Laboratory follow-up was six-monthly and included CD4 cell counts and other haematological measurements. The diagnosis of opportunistic infectionbss was either definitive or presumptive based on CDC guidelines. Treatment was available for all opportunistic infectionss except for cytomegalovirus (CMV) infection.
CD4 cell count declines were examined in three CD4 count strata and were fastest in patients with above 500 CD4 cells/mm3 and slower in the lower CD4 count strata. The CD4 decline had a significant direct association with the baseline CD4 cell count but not with age, sex, race, or AZT monotherapy. The incidence of specific opportunistics was determined for only patients with two or more CD4 cell counts.
The incidence of all opportunistic infections was higher at lower CD4 cell counts with the highest rate in the CD4 stratum below 50 cells/mm3. Specific OIs were associated with distinct CD4 cell count strata. Tuberculosis (TB) and oral candidiasis were the predominant opportunistic infectiinonss for CD4 counts above 200 cells/mm3 and were the only OIs for CD4 counts above 500 cells/µmm3. Significantly, TB was associated with all CD4 count strata while cryptococcal disease was predominant below 50 cells/mm3.
The strength of the South African study lies in the fact that it had a large cohort with both sexes and various ethnic groups represented. However, the study had several limitations. First, only 50 % of the recruited patients were eligible for the incidence study. Second, mean CD4 cell counts were not stratified according to the viral load because this data was unavailable. Finally, the history of previous opportunistic infectionss was not available; it was not possible to rule out the possibility that the reported incidence rates was due to recurrence.
These are novel and exciting findings which must be validated in other African settings with an escalating HIV/AIDS problem. The data suggest that targeted prophylaxis of specific opportunistic infectionss could be initiated as a function of the CD4 cell count. The data could provide the scientific basis for guidelines for the timing of prophylaxis in Africa.
The immediate policy implications of the study is that isoniazid prophylaxis for TB must commence early, CTX prophylaxis should be maintained in patients with a CD4 cell count below 200 cells/mm3, and prophylaxis against cryptococcal disease is imperative at below 50 CD4 cells/mm3.
Resource-poor clinics providing health care to HIV-positive patients lack facilities for measuring CD4 counts. The authors measured total lymphocyte counts (TLC) but did not report on the usefulness of TLC for predicting the incidence of opportunistic infections. TLC assays are simple and sustainable and TLC might be useful in guiding the care of HIV-positive patients in resource-poor settings.
Targeted opportunistic infection prophylaxis is a beacon of hope for HIV-positive patients with no access to antiretroviral therapy. In this study CD4 count is used to guide clinical decision-making. TLC might be cheaper and more sustainable in many African countries.
Holmes CB et al. CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: implications for prophylaxis and treatment. J Acquir Immune Defic Syndr 42 (4): 464-469, 2006.