Clinical and Demographic Factors Associated With Kaposi Sarcoma-Associated Herpesvirus Shedding in Saliva or Cervical Secretions in a Cohort of Tanzanian Women.

Background: Reasons for the high prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods: We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results: Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P = .009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions: In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6.

Cascade of care for HIV-seroconverters in rural Tanzania: a longitudinal study.

We examined the HIV care cascade in a community-based cohort study in Kisesa, Magu, Tanzania. We analyzed the proportion achieving each stage of the cascade - Seroconversion, Awareness of HIV status, Enrollment in Care and Antiretroviral therapy (ART) initiation - and estimated the median and interquartile range for the time for progression to the next stage. Modified Poisson regression was used to estimate prevalence risk ratios for enrollment in care and initiation of ART. From 2006 to 2017, 175 HIV-seroconverters were identified. 140 (80%) knew their HIV status, of whom 97 (69.3%) were enrolled in HIV care, and 87 (49.7%) had initiated ART. Time from seroconversion to awareness of HIV status was 731.3 [475.5-1345.8] days. Time from awareness to enrollment was 7 [0-64] days, and from enrollment to ART initiation was 19 [3-248] days. There were no demographic differences in enrollment in care or ART initiation. Efforts have been focusing on shortening time from seroconversion to diagnosis, mostly by increasing the number of testing clinics available. We recommend increased systematic testing to reduce time from seroconversion to awareness of status, and by doing so speed up enrollment into care. Interventions that increase enrollment are likely to have the most impact in achieving UNAIDS targets.

HIV-seroconversion among HIV-1 serodiscordant married couples in Tanzania: a cohort study.

BACKGROUND: Heterosexual transmission is the main driver of the HIV epidemic in Tanzania. Only one estimate of the incidence rate of intra-marital HIV seroconversion in Tanzania has been reported and was derived from data collected between 1991 and 1995. Moreover, little is known about the specific risk factors for intra-marital seroconversion in Tanzania. Improved evidence around factors that increase the risk of HIV transmission to a serodiscordant spouse is needed to develop and improve evidence-based interventions. We sought to investigate the rate of intra-marital HIV seroconversion among HIV sero-discordant couples in Tanzania as well as its associated risk factors. METHODS: We identified all HIV positive individuals in the TAZAMA HIV-serosurvey cohort and followed up their serodiscordant spouse from 2006 to 2016. The rate of seroconversion was analyzed by survival analysis using non-parametric regressions with exponential distribution. RESULTS: We found 105 serodiscordant couples, 14 of which had a seroconverting spouse. The overall HIV-1 incidence rate among spouses of people with HIV-1 infection was 38.0 per 1000 person/years [22.5-64.1]. Notably, the HIV-1 incidence rate among HIV-1 seronegative male spouses was 6.7[0.9-47.5] per 1000 person/years, compared to 59.3 [34.4-102.1] per 1000 person/years among female spouses. Sex of the serodiscordant spouse was the only significant variable, even after adjusting for other variables (Hazard rate = 8.86[1.16-67.70], p = 0.036). CONCLUSIONS: Our study suggests that rates of HIV-1 seroconversion of sero-discordant partners are much higher within marriage than in the general population in Tanzania. The major risk factor for HIV-1 seroconversion is sex of the serodiscordant spouse, with female spouses being at very high risk of acquiring HIV infection. This suggests that future programs that target serodiscordant couples could be a novel and effective means of preventing HIV-1 transmission in Tanzania.

Impact of schistosome infection on long-term HIV/AIDS outcomes.

BACKGROUND: Africa bears the burden of approximately 70% of global HIV infections and 90% of global schistosome infections. We sought to investigate the impact of schistosome infection at the time of HIV-1 seroconversion on the speed of HIV-1 disease progression, as measured by the outcome CD4+ T-cell (CD4) counts <350 cells/µL and/or death. We hypothesized that people who had been infected with Schistosoma spp. at the time they acquired HIV-1 infection would have impaired antiviral immune response, thus leading them to progress twice as fast to a CD4 count less than 350 cells/µL or death than would people who had been free of schistosomes at time of HIV-1 seroconversion. METHODS AND PRINCIPAL FINDINGS: We conducted a longitudinal study in Tanzania from 2006 to 2017 using stored blood spot samples, demographic surveillance and sero-survey data from the community, and a review of clinical charts. A competing risk analysis was performed to look at the difference in time to reaching CD4 counts < 350 cells/µL and/or death in HIV-1-infected people who were infected versus not infected with Schistosoma spp. at time of HIV-1 seroconversion. We found an 82% reduction in risk of reaching the outcome in seroconverters who had been infected with Schistosoma (subHazard Ratio = 0.18[0.068,0.50], p = 0.001) after adjusting for age, occupation, clinic attendance and time-dependent covariates. CONCLUSIONS: Our study demonstrates that people with schistosome infection at the time of HIV-seroconversion develop adverse HIV outcomes more slowly than those without. The findings are contrary to our original hypothesis. Our current longitudinal findings suggest complex interactions between HIV-1 and schistosome co-infections that may be modulated over time. We urge new immunological studies to investigate the long-term impact of schistosome infection on HIV-1 viral load and CD4 counts as well as related immunologic pathways.

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

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] log10 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.

Correlation of serum and dried blood spot results for quantitation of Schistosoma circulating anodic antigen: a proof of principle.

Circulating anodic antigen (CAA) testing is a powerful, increasingly-used tool for diagnosis of active schistosome infection. We sought to determine the feasibility and reliability of measuring CAA in blood spots collected on Whatman 903 protein saver cards, which are the predominant filter papers used worldwide for dried blood spot (DBS) research and clinical care. CAA was eluted from blood spots collected from 19 individuals onto Whatman 903 cards in Mwanza, Tanzania, and the assay was optimized to achieve CAA ratios comparable to those obtained from the spots' corresponding serum samples. The optimized assay was then used to determine the correlation of serum samples (n=16) with DBS from cards that had been stored for 8 years at ambient temperature. Using a DBS volume equivalent to approximately four times the quantity of serum, CAA testing in DBS had a sensitivity of 76% and a specificity of 79% compared to CAA testing in serum. CAA testing was reliable in samples eluted from Whatman 903 cards that had been stored for 8 years at ambient temperature. The overall kappa coefficient was 0.53 (standard error 0.17, p<0.001). We conclude that CAA can be reliably and accurately measured in DBS collected onto the filter paper that is most commonly used for clinical care and research, and that can be stored from prolonged periods of time. This finding opens new avenues for future work among more than 700million individuals living in areas worldwide in which schistosomes are endemic.