Herpes Simplex Virus Type 2 Prevalence and Association with Inflammatory Cytokines Among Sexual and Gender Minorities Living With and Without HIV-1 from Lagos, Nigeria

Abstract

Herpes simplex virus type 2 (HSV-2) is common globally and contributes significantly to the risk of acquiring HIV-1, yet these two sexually transmitted infections have not been sufficiently characterized for sexual and gender minorities (SGM) across Sub-Saharan Africa. To help fill this gap, we performed a retrospective study using plasma and serum samples from 183 SGM enrolled at the Lagos site of the TRUST/RV368 cohort in Nigeria, assayed them for HSV-2 antibodies with the Kalon ELISA and plasma cytokines and chemokines with Luminex, and correlated the findings with HIV-1 viral loads (VLs) and CD4 counts. We found an overall HSV-2 prevalence of 36.6% (49.5% and 23.9% among SGM with and without HIV-1, respectively, p < .001). Moreover, HSV-2-positive status was associated with high circulating concentrations of CCL11 among antiretroviral therapy-treated (p = .031) and untreated (p = .015) participants, and with high concentrations of CCL2 in the untreated group (p = .004), independent of VL. Principal component analysis revealed a strong association of cytokines with HIV-1 VL independent of HSV-2 status. In conclusion, our study finds that HSV-2 prevalence among SGM with HIV-1 is twice as high than HSV-2 prevalence among SGM without HIV-1 in Lagos and suggests that this is associated with higher levels of certain systemic cytokines. Additional work is needed to further characterize the relationship between HSV-2 and HIV-1 in SGM and help develop targeted therapies for coinfected individuals.

Keywords: HIV; HSV-2; STI; anorectal; inflammation.

FIG. 1.

HIV-1 VLs and CD4 counts. (A) Plasma HIV-1 RNA copies/mL and (B) CD4 counts (Median with 95% CI) are presented. “+” indicates HSV-2 positive and “−” indicates HSV-2 negative. Each symbol represents an individual participant. Asterisks indicate p value <.0001. ART, antiretroviral therapy; CI, confidence interval; HSV-2, herpes simplex virus type 2; VLs, viral loads.

FIG. 2.

Plasma concentrations of cytokines and chemokines. Plasma from one participant (−ART/+HSV-2 group) was not available, data from one participant (−ART/+HSV-2 group) did not pass QC (low bead count) and were excluded. Data from one participant were excluded since it was run with the ART participants. Data representing 88 plasma samples derived from HIV+ SGM (−ART/−HSV-2 = 31, −ART/+HSV-2 = 24, +ART/−HSV-2 = 13, +ART/+HSV-2 = 20) are shown. Each symbol indicating an individual participant and Median values are presented. Dotted lines represent LLOQs in two Luminex assays. Each symbol indicates an individual participant. *Indicate p value <.05, **Indicate p value <.01. LLOQs, lower limits of quantification; QC, quality control; SGM, sexual and gender minorities.

FIG. 3.

Log-linear relationships among HIV-1 VL, CD4 counts, and PC1 (A) and PC2 (B). Within each PCA, associations between first 3 principal components and HIV-1 VL and CD4 counts were analyzed. Significant associations were identified only within PC1 and PC2. Each symbol represents an individual participant. PC1, principal component 1; PC2, principal component 2; PCA, principal component analysis.