Abstract:

Introduction: Little 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 findings: We 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/Significance: Our 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.

Author summary: Schistosoma sp. are parasitic worms that infect at least 218 million people worldwide. Over 90% of these individuals live in Africa, where HIV infection is also endemic. Schistosome worms lay eggs that damage the gastrointestinal and genitourinary tracts, causing extensive morbidity and mortality. Patients who have HIV and Schistosoma mansoni co-infections are at risk for damage to the liver due to both the effects of the schistosome parasite and the side-effects of antiretroviral therapy. However, little is known about the additional liver effects of schistosome infection in patients already taking antiretroviral therapy. Therefore, we conducted a study in northwest Tanzania, where our prior work has shown that approximately one-third of HIV-infected patients also have schistosome infections, to investigate the effect of co-infection with Schistosoma mansoni on liver damage in patients taking antiretroviral therapy. We studied 305 HIV-infected outpatients on medium and long-term antiretroviral therapy and determined both liver damage and S.mansoni infection in those patients. We found that among patients on antiretroviral therapy, those with HIV-schistosome co-infection were 3 times more likely to have liver damage than those with HIV infection alone. Our work shows the importance of screening and treating for Schistosoma mansoni to decrease the risk of liver damage in patients infected with HIV.