Incidence of malaria by cotrimoxazole use in HIV-infected Ugandan adults on antiretroviral therapy

Abstract

Introduction:Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial.Methods:HIV-infected Ugandan adults stable on ART and CTX with CD4+ cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes.Results:A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2–10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74–4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18–0.49). There was one malaria-related death (CTX arm).Conclusion:HIV-infected adults – who are stable on ART and stop prophylactic CTX – experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis.

Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria

“…However, our conclusion was in consonance with the study reported that malaria occurrence did not differ by CD4 count at ART initiation, enrolment or during follow up [46]. Hence immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence [46]. …”

Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study

“…This study used data gathered during the COSTOP trial conducted from 2011 to 2014 in Uganda (ISRCTN44723643). Trial methods have been described previously [ 19 , 21 ]. Briefly, COSTOP was a randomized, double-blind, placebo controlled non-inferiority trial to determine whether long-term prophylaxis with CTX can be safely discontinued among HIV infected adults on ART with sustained immune competence (defined as a confirmed CD4 counts of ≥250 cells/µl).…”

“…Clinical malaria was defined as presence or history (during the previous 2 weeks) of fever and microscopically confirmed malaria parasites. Severe malaria (based on WHO guidelines) [ 21 , 22 ] was diagnosed if a participant had Plasmodium falciparum asexual parasitaemia, no other obvious cause of symptoms and met any of the following criteria: convulsions, loss of consciousness, hypotension (systolic blood pressure <70 mmHg), admission to hospital due to malaria, laboratory evidence of liver or kidney damage, severe normocytic anaemia (haemoglobin <50 g/dl, PCV < 15 %), or hyper parasitaemia on blood slide (>5 % or 250,000/µl).…”

“…To address these research questions, we conducted a planned sub-group analysis to examine the relationship of CD4 count with malaria in the recently completed COSTOP trial in Uganda [ 19 – 21 ]. COSTOP was a randomized, placebo-controlled, non-inferiority trial assessing the efficacy and safety of stopping CTX prophylaxis among HIV positive adults who were stable on ART.…”

“…COSTOP was a randomized, placebo-controlled, non-inferiority trial assessing the efficacy and safety of stopping CTX prophylaxis among HIV positive adults who were stable on ART. The trial found that malaria incidence was higher among those who were randomized to stop prophylactic CTX [ 21 ]. Data from this trial were used to investigate the effect of CD4 count on the incidence of malaria, and whether the effect of CD4 count on malaria differed by CTX use.…”