Herpes Simplex Virus Type 2 Status Research Articles

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.

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.

Vaginal and Penile Microbiome Associations With Herpes Simplex Virus Type 2 in Women and Their Male Sex Partners

BackgroundWe determined how the vaginal and penile microbiomes contribute to herpes simplex virus type 2 (HSV-2) serostatus within sexual partnerships.MethodsMicrobiomes were characterized in cervicovaginal lavage and penile meatal swab specimens through high-throughput 16s ribosomal RNA gene amplicon sequencing. HSV-2 antibody was detected in serum specimens. We modeled vaginal and penile taxa and covariates contributing to HSV-2 status in women and men using bivariate probit analysis.ResultsAmong 231 couples, HSV-2 was detected in both partners in 78 couples (33.8%), in the woman only in 52 (22.5%),in the man only in 27 (11.7%), and in neither in 74 (32.0%). Among the women (median age, 22 years) 10.9% had human immunodeficiency virus (HIV), and 21.4% had Bacterial vaginosis. Among men (median age, 26 years), 11.8% had HIV, and 55.0% circumcised. In an analysis with adjustment for sociodemographics and Bacterial vaginosis, enrichment of vaginal Gardnerella vaginalis and Lactobacillus iners was associated with increased likelihood of HSV-2 in both partners. Penile taxa (including Ureaplasma and Aerococcus) were associated with HSV-2 in women.ConclusionsWe demonstrate that penile taxa are associated with HSV-2 in female partners, and vaginal taxa are associated with HSV-2 in male partners. Our findings suggest that couples-level joint consideration of genital microbiome and sexually transmitted infection or related outcomes could lead to new avenues for prevention.

Herpes Simplex Virus Type 2 Seroprevalence Among Different National Populations of Middle East and North African Men.

There are limited data on herpes simplex virus type 2 (HSV-2) seroprevalence in the Middle East and North Africa (MENA). We examined country- and age-specific HSV-2 seroprevalence among select MENA populations residing in Qatar. Sera were collected from male blood donors attending Hamad Medical Corporation between June 2013 and June 2016. Specimens were screened for anti-HSV-2 IgG antibodies following a 2-test algorithm: HerpeSelect 2 ELISA was used to identify HSV-2-positive specimens, and Euroline-WB was used to confirm positive and equivocal specimens for final HSV-2 status. Trends and associations with HSV-2 seropositivity were assessed. Of the 2077 tested sera, 61 were found and confirmed positive. The proportion of those confirmed positive increased steadily with HerpeSelect 2 ELISA index value, ranging from 16.3% for index values of 1.101 to 1.999 to 92.9% for index values of 4 or greater. Nationality-specific seroprevalence was 6.0% (95% confidence interval [CI], 4.1%-8.8%) in Qataris, 5.3% (95% CI, 2.5%-11.1%) in Iranians, 4.2% (95% CI, 1.8%-9.5%) in Lebanese, 3.1% (95% CI, 1.2%-7.7%) in Sudanese, 3.0% (95% CI, 1.4%-6.4%) in Palestinians, 2.2% (95% CI, 1.1%-4.3%) in Egyptians, 2.0% (95% CI, 1.0%-5.0%) in Syrians, 1.0% (95% CI, 0.3%-3.6%) in Jordanians, 0.7% (95% CI, 0.1%-3.7%) in Yemenis, and 0.5% (95% CI, 0.1%-2.8%) in Pakistanis. There was evidence for higher seroprevalence in older age groups. The seroprevalence of HSV-2 was in the range of few percentage points. There were no major differences in seroprevalence by nationality. These findings add to our understanding of HSV-2 epidemiology in MENA and indicate unmet needs for sexual health and control of sexually transmitted infections.

Differences in health-related quality of life between HIV-positive and HIV-negative people in Zambia and South Africa: a cross-sectional baseline survey of the HPTN 071 (PopART) trial.

SummaryBackgroundThe life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa.MethodsAs part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use.FindingsWe obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score −0·002, 95% CI −0·01 to 0·001; p=0·219) nor in South Africa (0·000, −0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individuals who had initiated ART less than 5 years previously and HIV-negative individuals in Zambia (−0·006, 95% CI −0·008 to −0·003; p<0·0001). A large proportion of people with clinically confirmed HIV were unaware of being HIV-positive (1768 [43%] of 4128 people in Zambia and 2026 [50%] of 4012 people in South Africa) and reported good HRQoL, with no significant differences from that of HIV-negative people (change in mean HRQoL score −0·001, 95% CI −0·003 to 0·001, p=0·216; and 0·001, −0·001 to 0·001, p=0·997, respectively). In South Africa, HRQoL scores were lower in HIV-positive individuals who were aware of their status but not enrolled in HIV care (change in mean HRQoL −0·004, 95% CI −0·01 to −0·001; p=0·010) and those in HIV care but not on ART (−0·008, −0·01 to −0·004; p=0·001) than in HIV-negative people, but the magnitudes of difference were small.InterpretationART is successful in helping to reduce inequalities in HRQoL between HIV-positive and HIV-negative individuals in this general population sample. These findings highlight the importance of improving awareness of HIV status and expanding ART to prevent losses in HRQoL that occur with untreated HIV progression. The gains in HRQoL after individuals initiate ART could be substantial when scaled up to the population level.FundingNational Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, the Bill & Melinda Gates Foundation.

High Rates of Herpes Simplex Virus Type 2 Infection in Homeless Women: Informing Public Health Strategies.

Homeless and unstably housed women living in an urban setting are at risk for sexually transmitted diseases, yet the seroprevalence and correlates of herpes simplex virus type 2 (HSV-2) specific to impoverished women are poorly understood. Between April and October 2010, we conducted a cross-sectional analysis of sociodemographic, structural, and behavioral factors associated with prevalent HSV-2 infection (recent and historical infections) within a community-recruited cohort of homeless and unstably housed women. Logistic regression modeling was used to identify independent sociobehavioral correlates of HSV-2 infection. Among 213 women (114 HIV positive and 99 HIV negative), the median age was 49, 48% were African American, and 63% had completed high school. HSV-2 seroprevalence was 88%, and only 17% of infected women were aware of their infection. In adjusted analysis, odds of HSV-2 infection were significantly higher for those reporting at-risk drinking (adjusted odds ratio [AOR] = 7.04; 95% confidence interval [CI] = 1.59, 67.91), heterosexual orientation (AOR = 4.56; 95% CI = 1.81, 11.69), and for those who were HIV positive (AOR = 3.64; 95% CI = 1.43, 10.30). Odds of HSV-2 infection decreased as current income increased (AOR for each $500 monthly increase = 0.90; 95% CI = 0.78, 0.997). There is an extremely high seroprevalence of HSV-2 infection among homeless and unstably housed women, and most are unaware of their HSV-2 status. Screening all unstably housed women for HSV-2 infection, with additional counseling for sexual risk and alcohol use, may lead to the identification of more infections and be a first step in reducing additional disease transmission.

Herpes simplex virus type 2 among mobile pastoralists in northwestern Namibia

Background: Although herpes simplex virus type 2 (HSV-2) epidemiology has been described for many western and/or urban populations, disease burden has not been characterized for remote, non-western, under treated populations, where patterns of risk and vulnerability may be very different.Aims: To understand demographic, behavioural and geographic influences on risk for HSV-2 in a population of mobile, rural pastoralists in northwestern Namibia.Subjects and methods: The authors conducted a cross-sectional survey of reproductively aged adults (n = 445) across 28 villages in Kaokoveld, Namibia. All participants completed a questionnaire of demographic data, ecological interactions and sexual behaviour, and a rapid test specific for HSV-2.Results: HSV-2 status was significantly associated with being female (OR = 3.1, 95% CI = 2.00, 4.71), increasing age (men: OR = 7.5, 95% CI = 2.67, 20.85; women: OR = 6.2, 95% CI = 2.48, 15.50) and with higher wealth among men (OR = 5.1, 95% CI = 1.98, 13.09).Conclusions: Higher risk among women can be explained, in part, by local hygiene practices and a preference for “dry” sex. There was considerable variation in prevalence by region, which appears to be linked to geographic remoteness. Culturally contextualized epidemiologic studies of remote, vulnerable populations can provide essential information for limiting the introduction and spread of new infections.

Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.

Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2). To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition. Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245). Multiple sites in Kenya and Uganda. Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner. Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo. HSV-2 seroconversion. A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years. Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available. Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP. Bill & Melinda Gates Foundation.

Incident HSV-2 Infections Are Common Among HIV-1-discordant Couples

The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

P3.370 Daily Oral Emtricitabine/Tenofovir Pre-Exposure Prophylaxis and Prevention of HSV-2 Acquisition Among Heterosexual Men and Women

BackgroundDaily oral and pericoital tenofovir-based antiretroviral pre-exposure prophlyaxis (PrEP), reduced risk of HIV-1 acquisition in trials among high risk populations; oral emtricitabine(FTC)/tenofovir (TDF) received a label indication for HIV-1 prevention....

Herpes Simplex Virus Type 2 Coinfection Does Not Accelerate CD4 Count Decline in Untreated HIV Infection

Herpes simplex virus type 2 (HSV-2) reactivations are associated with increased HIV load, but whether HSV-2 coinfection accelerates HIV disease is unclear. We compared rates of CD4 count decline according to HSV-2 status in untreated HIV-infected adults. HIV-infected patients with a past period of antiretroviral therapy (ART)-untreated follow-up with initial CD4 count of 400-900 cells/mm(3) and no chronic anti-HSV therapy were included. HSV-2 status was determined by HerpeSelect enzyme-linked immunosorbent assay. Rates of CD4 count change were compared by HSV-2 status using mixed linear regression models, and time to the first of ART initiation or CD4 <350 cells/mm(3) using proportional hazards models. Of 218 patients included, 123 (56.4%) were seropositive for HSV-2 and 161 (73.8%) for HSV-1. In univariate analysis, the difference in the rate of CD4 count change associated with HSV-2 was not statistically significant at +13.6 cells/mm(3)/year (P = .12). Results were similar at -4.5 cells/mm(3)/year (P = .68) after adjustment for sex, HSV type 1, oral and genital herpes symptoms, immigrant status, and the interaction of immigrant status with time. However, HSV-2 seropositivity was associated with a shorter time to the first of ART initiation or CD4 <350 cells/mm(3), with an adjusted hazard ratio of 2.07 (95% confidence interval, 1.28-3.33). HSV-2 coinfection was not associated with the rate of CD4 count decline during ART-untreated HIV infection, but was associated with an earlier combined endpoint of ART initiation or CD4 <350 cells/mm(3). Attenuating effects of acyclovir on HIV disease progression observed in recent clinical trials may result from direct anti-HIV activity rather than indirect benefits from HSV-2 suppression.

Limited benefit of repeating a sensitive question in a cross-sectional sexual health study

BackgroundSexual health research relies heavily on self-reported data. We explored whether repeating a key measure – number of lifetime sexual partners – improved the validity of this self-reported response.MethodsUsing data from a study of Tanzanian plantation residents, we examined which of 505 participants changed their responses when a question about sexual partners was repeated. We examined which variable (first, second, or maximum response) was more predictive of herpes simplex virus type 2 (HSV-2) seropositivity, a biomarker strongly associated with number of lifetime partners. HSV-2 status was assessed using the HerpeSelect 2 ELISA IgG test.ResultsWhen asked a second time, 10.7% of participants increased and 3.6% decreased their reported number of partners. Participants using audio computer-assisted self-interviews were more likely to change than those interviewed in person (p = 0.006). The increased odds of HSV-2 seropositivity with each additional partner ranged from 10% to 13% in men, and 33% to 37% in women, depending on which partner variable was used. Estimates had considerable confidence interval overlap and no substantial differences in precision.ConclusionsSome participants change their responses when asked a sensitive question a second time, but in this population, changes did not meaningfully affect associations between lifetime partners and HSV-2.

Case-Crossover Analysis of Condom Use and Herpes Simplex Virus Type 2 Acquisition

Although growing evidence suggests that condoms offer moderate protection against herpes simplex virus type 2 (HSV-2), inability to control for unknown or unmeasured confounders associated with sexual activity may reduce the accuracy of the estimates. The case-crossover design offers increased control of individual-level confounders, and was thus used with the aim of producing a more accurate estimate of the effect of condom use on HSV-2 acquisition. Data were pooled from 6 prospective studies that measured HSV-2 status at enrollment and over follow-up, and included periodic self-reported condom use and sexual activity. Sexual activity contemporaneous with acquisition was assigned to a case period; earlier sexual activity was assigned to a control period. Conditional logistic regression was used to assess differences in behavior during the case and control periods. One hundred ninety-one eligible participants acquired HSV-2 during follow-up. This approach detected a 3.6% increase in the odds of HSV-2 acquisition with each unprotected act (odds ratio = 1.036; 95% confidence interval: 1.021-1.052), but no increase in the odds of acquisition associated with protected acts (odds ratio = 1.008; 95% confidence interval: 0.987-1.030). This analysis suggests that condoms offer significant protection against HSV-2 transmission.

Herpes Simplex Virus Type 2, Genital Ulcers and HIV-1 Disease Progression in Postpartum Women

BackgroundCo-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.MethodsHIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12–24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.ResultsAmong 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33–5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93–15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).ConclusionsHSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.

Effects of HIV-1 and Herpes Simplex Virus Type 2 Infection on Lymphocyte and Dendritic Cell Density in Adult Foreskins from Rakai, Uganda

Male circumcision reduces human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2) acquisition, and HSV-2 infection is associated with an increased risk of HIV acquisition. To assess the cellular basis for these associations, we estimated immunologic cellular densities in foreskin tissue. Immunostained CD1a(+) dendritic cell and CD4(+) and CD8(+) T cell densities were quantified in foreskin samples obtained from medical circumcision in Rakai, Uganda (35 HIV-infected, HSV-2-infected men; 5 HIV-infected, HSV-2-uninfected men; 22 HIV-uninfected, HSV-2-infected men; and 29 HIV-uninfected, HSV-2-uninfected men. CD1A(+) dendritic cell densities did not vary by HIV or HSV-2 status. Compared with densities in HIV-uninfected, HSV-2-uninfected men (mean, 26.8 cells/mm(2)), CD4(+) T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm(2)), were significantly decreased in the HIV-infected, HSV-2-uninfected group (mean, 11.2; P < .05), and were increased in the HIV-uninfected, HSV-2-infected group (mean, 68.7; P < .05). Dermal CD8(+) T cell densities were higher in the HIV and HSV-2-coinfected group (mean, 102.9) than in the HIV-uninfected, HSV-2-uninfected group (mean, 10.0; P < .001), the HIV-infected, HSV-2-uninfected group (mean, 27.3; P < .001), and the HIV-uninfected, HSV-2-infected group (mean, 25.3; P < .005). The increased CD4(+) cellular density in the HIV-uninfected, HSV-2-infected men may help to explain why HSV-2-infected men are at increased risk of HIV acquisition. The absence of this increase in men coinfected with both HIV and HSV-2 is likely in part the result of the progressive loss of CD4(+) cells in HIV infection. Conversely, HIV and HSV-2 coinfection appears to synergistically increase CD8(+) T cell densities.

Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials

Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC. HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43-0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51-0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30-0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (chi(2)p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15-0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19-1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49-1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0-38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI -1.2 to 77.1). Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.

Incident HIV and herpes simplex virus type 2 infection among men in Rakai, Uganda

Herpes simplex virus type 2 (HSV-2) infection is associated with an increased risk for acquiring HIV, but little is known about the temporal sequence of these infections. : Six thousand three hundred ninety-six men were evaluated for serologic HSV-2 and HIV infections and behaviors during a male circumcision trial in Rakai, Uganda. HIV and HSV-2 status were determined using enzyme-linked immunosorbent assays and confirmed by HIV-1 and HSV-2 western blots. A Poisson multivariable model was used to estimate adjusted incidence rate ratios of HIV acquisition associated with HSV-2 and other covariates. HIV incidence was 1.09/100 person-years and acquisition was associated with incident HSV-2 infection [adjusted incidence rate ratio (adjIRR) 5.28, 95% confidence interval (CI) 2.79-9.98], chronic HSV-2 infection (adjIRR 2.78, 95% CI 1.64-5.68), genital ulcer disease, urethral discharge, genital washing after intercourse, being unmarried, and being uncircumcised. Sixteen men acquired both HIV and HSV-2 during the trial: four acquired HIV first, three acquired HSV-2 first, and nine acquired both infections in the same follow-up interval. The findings suggest that unsafe sex places men at risk of both HIV and HSV-2 infections, and it is unclear whether HSV-2 acquisition is a cofactor for HIV infection or a marker of correlated sexual exposures. This reinforces the need for promotion of safe sex as the primary method of prevention of both viruses.

Effect of HSV‐2 Serostatus on Acquisition of HIV by Young Men: Results of a Longitudinal Study in Orange Farm, South Africa

The objectives of this study were to assess the impact among young men of herpes simplex virus type 2 (HSV-2) status on the acquisition of human immunodeficiency virus (HIV) and on the protective effect of male circumcision against HIV acquisition. We used data collected during a male circumcision trial conducted in Orange Farm, South Africa. We estimated adjusted incidence rate ratios (IRRs) for HIV acquisition, using survival analysis and background characteristics, HSV-2 status, male circumcision status, and sexual behavior as covariates. Compared with subjects who remained HSV-2 negative throughout the study, subjects who were HSV-2 positive at enrollment had an adjusted IRR of 3.3 (95% confidence interval [CI], 1.5-7.4; P=.004), and those who became HSV-2 positive during follow-up had an adjusted IRR of 7.0 (95% CI, 3.9-12.4; P<.001). The population fraction of incident HIV infection attributable to HSV-2 was 27.8% (95% CI, 17.7%-37.2%). Intention-to-treat analysis of the protective effect of male circumcision on HIV acquisition was the same among men with and men without HSV-2 (0.38 vs. 0.37; P=.93). This study shows that HSV-2 has a substantial impact on HIV acquisition among young South African men. It suggests that HSV-2 infection enhances HIV acquisition and is responsible for approximately 25% of incident cases of HIV infection. However, the protective effect of male circumcision against HIV acquisition appears independent of HSV-2 serostatus. ClinicalTrials.gov identifier: NCT00122525.

Herpes Simplex Virus Type‐Specific Serology: Where Does it Fit in the Diagnostic Armamentarium?

Herpes Simplex Virus Type‐Specific Serology: Where Does it Fit in the Diagnostic Armamentarium?

Cost-effectiveness of herpes simplex virus type 2 serologic testing and antiviral therapy in pregnancy

The purpose of this study was to determine whether serologic testing for herpes simplex virus type 2 (HSV-2) in pregnant women and their partners is cost-effective. A decision analysis model was developed to investigate the cost-effectiveness of providing type-specific serologic testing at week 15 of pregnancy for all women unaware of their HSV-2 status, and offering antiviral suppressive therapy from week 36 until delivery to all seropositive women. This scenario was compared with current care, in which only a minority of women diagnosed with genital herpes (GH) receives antiviral suppressive therapy (AST). In a third scenario, testing is offered to partners of pregnant women who test seronegative, and antiviral suppressive therapy is offered to the partners who test seropositive. Compared with current care, offering testing and antiviral suppressive therapy to 100,000 pregnant women resulted in an incremental cost of $3.1 million, 15.7 fewer cases of neonatal herpes, 186 fewer cesarean deliveries, and an incremental cost per quality-adjusted life- year gained (QALY) of $18,680. Offering testing and suppressive therapy to both the pregnant women and their partners resulted in an increased cost of $8.6 million, 16.8 fewer cases of neonatal herpes, 192 fewer cesarean deliveries, and an incremental cost per QALY of $48,946 compared with no testing. Compared with commonly accepted benchmarks for cost-effectiveness (<$50,000/QALY), type-specific HSV-2 serologic testing of pregnant women may be a cost-effective strategy.