Quantitative and qualitative correlates of cervicovaginal herpes simplex virus type 2 shedding among HIV-infected women in the Women's Interagency HIV Study

Abstract

Summary We identified demographic, clinical and biological determinants of herpes simplex virus type 2 (HSV-2) shedding among HIV-infected participants in the Women’s HIV Interagency Study (WIHS). Cervicovaginal lavage (CVL) specimens from 369 HIV-infected HSV seropositive women were tested with TaqMan polymerase chain reaction (PRC) for detection HSV-2 DNA. Seven percent of women tested positive for HSV-2 DNA in CVL. Significant correlates of the presence of HSV-2 DNA in CVL were being younger, African American or Hispanic race/ethnicity and injecting drugs in the past six months (P < 0.05). A borderline significant trend for reduced viral shedding with higher CD4+ T cell counts was observed (P = 0.08). All women who were never observed with any genital lesions and had consistently negative self-reported history of genital sores throughout the follow-up (n = 29, 8%) were negative for CVL HSV-2 DNA. HSV-2 DNA quantity was significantly associated with having frequent subsequent lesion recurrences (Spearman rho = 0.48, P = 0.016; adjusted prevalence ratio [APR] = 2.5, P = 0.012). Increasing the age of the host was inversely correlated with decreased viral shedding over time. However, a subset of older women continued to shed significant amounts of virus despite passage of time. This study provides genital HSV-2 DNA titre as a quantitative and symptom- and sign-based measures as qualitative predictors of HSV-2 shedding from the lower genital tract among HIV-infected women.

Herpes viruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract

“…While HIV-1 (p+0.04) and CMV (p<0.01)seminal sheddingwere associated with lower CD4+T-cell counts, consistent with previous reports[16,22], there was strong evidence that HSVshedding occurred at CD4+counts >500 cells/ ml (P = 0.01). These results contrast with a recent report[37],documentingborderline increased HSV-shedding in subjects with CD4+<500 cells/ml (p=0.08). On the other hand, the subjects in our study had relatively intact immune systems and did not include severely immunocompromised persons in whom the association between herpesviruses and HIV-1 shedding may be stronger.…”

Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital Herpes

“…All human samples and data were analyzed anonymously. All data used in the present analysis are contained within previously published studies [ 8 , 15 , 16 ].…”

“…In a subset of HIV-infected women, cervicovaginal lavage (CVL) specimens collected at enrollment were tested for HSV–2 DNA as previously described [ 16 ]. CVL specimens were collected by flushing the cervix with 10 mL sterile normal saline; 200μL of each specimen was tested for HSV–2 DNA using duplex quantitative realtime TaqMan polymerase chain reaction (qPCR).…”

“…To compare the proportions of women with viral shedding (defined as detectable HSV–2 DNA in the CVL specimen) by IFNL4 -ΔG/TT genotype, we calculated aORs, 95% CIs and p-values by logistic regression. Adjusted models included HIV status and race as covariates as these variables were associated with viral shedding previously [ 16 ]. Among the subset of women shedding virus, p-values for differences in the distribution of HSV–2 DNA levels titers by genotype were determined with the Kruskal-Wallis test.…”

Accurate measurement of female genital tract fluid dilution in cervicovaginal lavage samples

“…Proteomic studies also have been conducted using CVL samples [11]. Molecular methods have been used to measure the abundance of viral pathogens in CVL samples, including: human papillomavirus (HPV) [12, 13], hepatitis C virus (HCV) [14], herpes simplex virus type 2 (HSV-2) [15-18], human immunodeficiency virus type 1 (HIV-1) [7, 15, 19], and cytomegalovirus (CMV) [20]. CVL samples from women volunteers have been analyzed to determine whether topical zinc deficiency is a risk factor in recurrent vulvovaginal candidiasis [21] and if dissolved nitric oxide gas is associated with bacterial vaginosis (BV) [22].…”