Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study

Abstract

Background

Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion.

Methodology/Principal findings

We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants’ consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2–6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3–1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9–4.6] log ₁₀ copies/mL versus 3.7 [3.2–4.3], p = 0.017.

Conclusions/Significance

We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.

Author summary

Schistosomiasis is a neglected tropical parasitic worm infection that affects 218 million people worldwide, the majority of whom live in Africa. Studies have shown that women with schistosomiasis tend to have higher rates of HIV infection, but until now no study has followed people over time to determine whether schistosomiasis increases a person’s risk of becoming HIV-infected. In this ongoing community study in rural Tanzania, we identified 73 individuals who became HIV-infected during follow-up, and 265 control individuals who were similar in age, sex, and location but who remained HIV-uninfected during follow-up. We tested these individuals’ stored blood samples to determine whether they had schistosome infection before they became HIV-infected. We found that women who had schistosome infections had a 2.8-fold increased risk of becoming HIV-infected compared to women without schistosome infections. We found no evidence of increased HIV acquisition in men with schistosome infections. We also found that the concentration of HIV in the blood shortly after people became HIV-infected was higher in those who had schistosome infections than in those who did not have schistosome infections. Our study suggests that schistosomiasis may play a major role in HIV transmission and disease progression in African countries.