IntroductionLittle is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without.Methodology/Principal findingsWe determined the presence and grade of hepatotoxicity among 305 HIV-infected outpatients who had been on medium-term (3–6 months) and long-term (>36 months) antiretroviral therapy in a region of northwest Tanzania where S. mansoni is hyperendemic. We used the AIDS Clinical Trial Group definition to define mild to moderate hepatotoxicity as alanine aminotransferase, alanine aminotransferase, and/or bilirubin elevations of grade 1 or 2, and severe hepatotoxicity as any elevation of grade 3 or 4. We determined schistosome infection status using the serum circulating cathodic antigen rapid test and used logistic regression to determine factors associated with hepatotoxicity. The prevalence of mild-moderate and severe hepatotoxicity was 29.6% (45/152) and 2.0% (3/152) in patients on medium-term antiretroviral therapy and 19.6% (30/153) and 3.3% (5/153) in the patients on long-term antiretroviral therapy. S. mansoni infection was significantly associated with hepatotoxicity on univariable analysis and after controlling for other factors associated with hepatotoxicity including hepatitis B or C and anti-tuberculosis medication use (adjusted odds ratio = 3.0 [1.6–5.8], p = 0.001).Conclusions/SignificanceOur work demonstrates a strong association between S. mansoni infection and hepatotoxicity among HIV-infected patients on antiretroviral therapy. Our study highlights the importance of schistosome screening and treatment for patients starting antiretroviral therapy in schistosome-endemic settings. Additional studies to determine the effects of schistosome-HIV co-infections are warranted.

BackgroundSchistosoma sp. infection has been shown to interact with HIV-1 by modifying susceptibility to the virus and impacting AIDS outcome, but very little is known about the potential impact of Schistosoma sp. infection on the efficiency of antiretroviral treatment (ART) in HIV-1 infected individuals. One study suggested increased immunological failure in patients infected with schistosomes compared to those uninfected. To our knowledge, no report exists on the virological response to ART in schistosome-infected individuals. In addition, viral load in HIV-1 infected individuals changes over the course of the HIV infection. This study assessed the impact of HIV-1/Schistosoma sp. co-infections on viral load in people with immunological failure on ART, taking into account the duration of HIV-1 infection.MethodsWe enrolled HIV-1 infected Tanzanian adults over 18 years of age who had used first line ART for more than 6 months and were identified to have immunological failure by the WHO criteria (50% drop from peak CD4 count, or CD4 count equal to or below baseline after 6 months of ART, or CD4 count below 100cells/mm3 after 1 year of ART). Patients were also tested for schistosome infection by microscopy for ova in urine and stool and by circulating anodic antigen (CAA) levels in serum. The duration of HIV-1 infection was calculated using baseline CD4+ T-cell (CD4) counts determined at enrollment. Univariable and multivariable analyses were conducted to compare viral loads in schistosome infected and uninfected patients.ResultsA total of 188 patients were enrolled. After univariable analysis, female sex, lower peak CD4 counts, lower current CD4 counts, anemia, and shorter time infected with HIV-1 were all significantly associated with higher viral load. Schistosome infection was not associated with viral load even after adjusting for sex, current CD4 counts and duration of HIV-1 infection.ConclusionsThe current study of HIV-infected patients with immunological failure on ART suggests that once ART is introduced, ART is the dominant driver of viral load and schistosome infection may no longer have an impact.