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

<div><p>Background</p><p>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.</p><p>Methodology/Principal findings</p><p>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 <i>Schistosoma mansoni</i> infection, and 2% has <i>S</i>. <i>haematobium</i>. 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] log₁₀ copies/mL versus 3.7 [3.2–4.3], p = 0.017.</p><p>Conclusions/Significance</p><p>We confirm, in an area with endemic <i>S</i>. <i>mansoni</i>, 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.</p></div

Median log₁₀ whole blood HIV-1 RNA levels in recent HIV-1 seroconverters with and without schistosome infection.

<p>Summary plot depicting median and interquartile range of log₁₀ of whole blood HIV-1 RNA level in copies/mL as quantitated from dried blood spots in recent HIV-1 seroconverters with or without schistosome infection. The median viral load was 4.4 [3.9–4.6] HIV-1 RNA log copies/mL in those with schistosome infection versus 3.7 [3.2–4.3] among those without (p = 0.017 by Wilcoxon rank-sum test).</p

Prevalence of schistosome infection among HIV-1 seroconverters and matched controls, stratified by gender.

<p>In women, 44% of HIV-1 seroconverters had schistosome infection, compared to 30% of controls (p = 0.019). In men, 29% of HIV-1 seroconverters had schistosome infection, compared to 38% of controls (p = 0.42). These differences were not detectable when cases and controls were analyzed without stratification by gender.</p

Demographic and behavioral characteristics of HIV-1-infected cases and HIV-uninfected controls, by gender.

<p>Demographic and behavioral characteristics of HIV-1-infected cases and HIV-uninfected controls, by gender.</p