Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study.
BACKGROUND
The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX).


METHODS
This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use.


RESULTS
2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30.


CONCLUSIONS
The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.
['Kasirye|Ronnie|R|0000-0002-5200-464X', 'Grosskurth|Heiner|H|', 'Munderi|Paula|P|', 'Levin|Jonathan|J|', 'Anywaine|Zacchaeus|Z|', 'Nunn|Andrew|A|', 'Kamali|Anatoli|A|', 'Baisley|Kathy|K|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D044966:Anti-Retroviral Agents D000962:Antimalarials D023241:Antiretroviral Therapy, Highly Active D018791:CD4 Lymphocyte Count D015496:CD4-Positive T-Lymphocytes D018890:Chemoprevention D004311:Double-Blind Method D005260:Female D005500:Follow-Up Studies D015658:HIV Infections D006801:Humans D015994:Incidence D008288:Malaria D008297:Male D008875:Middle Aged D010919:Placebos D015662:Trimethoprim, Sulfamethoxazole Drug Combination D014454:Uganda D055815:Young Adult
CD4 Cotrimoxazole Malaria Antiretroviral therapy HIV