Concordant HIV infection and visceral leishmaniasis in Ethiopia: The influence of antiretroviral treatment and other factors on outcome

Background. Coinfection with human immunodeficiency virus (HIV) and Leishmania donovani visceral leishmaniasis (VL) in Africa is an emerging, poorly understood disease. Methods. We evaluated 356 consecutive patients coinfected with HIV and VL treated in Humera, northwest Ethiopia, from February 2003 to October 2006, for risk factors for VL relapse and death and the effect of antiretroviral therapy (ART). Results. During 2928 patient-months of follow-up, 256 VL episodes and 39 deaths occurred. Among 195 patients receiving ART, 31.3% had >= 1 VL episode, and 14.4% died. Among 161 patients who did not receive ART, 26.1% had >= 1 VL episodes, and 6.8% died. A total of 54 patients who received ART and 58 patients who did not receive ART had >= 1 VL relapse. VL relapse among patients receiving ART was associated with a baseline CD4 cell count <100 cells/mu L (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.21-5.15) and >= 2 previous VL episodes (HR, 3.74; 95% CI, 1.40-10.02). Failure to clear parasites after VL treatment was usually followed by symptomatic VL relapse. Patients who relapsed showed poor CD4 cell count recovery while receiving ART. ART was partially protective against VL relapse (HR, 0.46; 95% CI, 0.26-0.82). However, 28% of first VL relapses while receiving ART occurred despite a CD4 cell count >200 cells/mu L; in 5% of VL relapses, the CD4 cell count had been >200 cells/mu L for 16 months. Factors associated with all-cause mortality among patients receiving ART were baseline CD4 cell count <100 cells/mu L (HR, 3.20; 95% CI, 1.30-7.87) and VL episodes during follow-up (HR for 1 episode, 4.97 [95% CI, 2.09-11.86]; HR for 12 episodes, 3.22 [95% CI, 1.01-10.23]). Conclusions. Concordant HIV infection and VL is a major, acquired immunodeficiency syndrome-defining illness with high relapse and mortality rates; ART reduces relapses; and secondary antileishmanial prophylaxis may benefit patients at risk of relapse.