Herpes Simplex Virus Type 2 Seroconversion Research Articles

Tenofovir Gel for Prevention of Herpes Simplex Virus Type 2 Acquisition: Findings From the VOICE Trial.

Genital infection with herpes simplex virus type 2 (HSV-2) is common and increases risk of human immunodeficiency virus (HIV) transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 study. We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blinded, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 preexposure prophylaxis. The TFV level in plasma at the first quarterly visit was used as a measure of gel use. Of 566 participants at risk for HSV-2 acquisition, 532 (94%) had first-quarter plasma TFV and end-of-study HSV-2 serologic data available. Over a follow-up period of 501 person-years, 92 incident cases of HSV-2 acquisition occurred: 77 were in women with no TFV detected in plasma, and 15 occurred in women with TFV detected in plasma (incidence, 20.6 cases/100 person-years [95% confidence interval [CI], 16.2-25.7] vs 11.9 cases/100 person-years [95% CI, 6.6-19.6], respectively). TFV detection in plasma was associated with a trend toward a reduced risk of HSV-2 seroconversion, with an unadjusted hazard ratio (HR) of 0.59 (95% CI, .34-1.02; P = .060) and a HR adjusted for site, age, having ≥2 male sex partners in the past 3 months, use of hormonal contraception, having anal sex in the past 3 months, and HIV status of 0.60 (95% CI, .33-1.08; P = .086). Detection of TFV in plasma among TFV gel users was associated with a trend toward a reduced risk of HSV-2 acquisition, after controlling for sexual behavior and HIV-1 acquisition.

No Role of Herpes Simplex Virus Type 2 (HSV-2) Infection on HIV Progression in Naïve HIV Patients

Background:Herpes simplex virus type 2 (HSV-2) is a common infection in human immunodeficiency virus (HIV) patients and may accelerate HIV progression by rising HIV viral load and decreasing CD4 count. However, the available data regarding the influence of HSV-2 seropositivity on HIV progression in HIV individuals are inconclusive. Therefore, we aimed to determine HSV-2 seroprevalence in naïve HIV patients and normal controls and also investigate the relation of HIV viral load and CD4 count with HSV-2 seropositivity. Subsequently, we investigated the association of HSV-2 serostatus with changing in CD4 count and HIV viral load in our subjects, after one year follow-up.Methods:In this study, 116 naïve HIV patients and 85 healthy controls from Tehran, Iran were enrolled. HSV-2 IgG antibody was detected by ELISA. CD4 count was determined by flowcytometry, and serum HIV RNA copy numbers were determined using real-time PCR.Results:The prevalence of HSV-2 IgG was 18.1% in naïve HIV patients and 0% in the control group (P = 0.000). HSV-2 seroconversion was observed in 2.43% of HIV patients after one year. There was no significant difference regarding HSV-2 serostatus with CD4 count and HIV RNA viral load in our study cohort at baseline and after one year.Conclusion:Our results revealed that the prevalence and incidence of HSV-2 infection are low in our HIV cases, and it is negligible in the control group. However, it seems that HIV/HSV2 co-infection has no role on HIV infection acceleration.

Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy: Results From the ACTG A5175 PEARLS Study.

Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants. HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen. Of 365 HSV-2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63 cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence interval, .55-1.44). HSV-2 acquisition was not reduced in HIV-infected, HSV-2-uninfected persons during TDF-containing ART.

Incidence and risk factors for herpes simplex virus type 2 seroconversion among pregnant women in Uganda: A prospective study.

Herpes simplex virus type 2 (HSV-2) acquired during pregnancy is associated with adverse outcomes such as perinatal HSV-2 transmission. HSV-2 seroconversion occurs within four weeks of HSV-2 acquisition. There was neither documented incidence nor risk factors for HSV-2 seroconversion during pregnancy in Uganda. The objective of this study was to determine the incidence and risk factors for HSV-2 seroconversion among pregnant women in Mulago Hospital, Uganda. A prospective study of 200 consenting HSV-2-negative women between 26 and 28 weeks of gestation was done between November 2013 and October 2014. HSV-2 serostatus was determined using HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA). Interviewer-administered questionnaires were used to collect socio-demographic characteristics and sexual history. Human immunodeficiency virus (HIV) serostatus was obtained from antenatal records. A total of 191 women completed follow-up and repeat HSV-2 serology by 38 weeks. Negative binomial regression analysis was used to estimate risk ratios for risk factors for HSV-2 seroconversion. Of 191 women, 15 (7.9%) seroconverted during pregnancy. Having multiple sexual partners, being in polygamous unions, and having HIV-positive serostatus were found to be risk factors for HSV-2 seroconversion. The incidence of HSV-2 seroconversion during pregnancy in Uganda was high. Multiple sexual partners, polygamy, and HIV-positive serostatus were risk factors for HSV-2 seroconversion during pregnancy. Strengthening health education on the avoidance of multiple sexual partners during pregnancy is paramount in prevention of HSV-2 seroconversion.

Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection

BackgroundGlobally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections.MethodsWe assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing.ResultsThe HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005).ConclusionsIn this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.)

Risk factors for incident HSV-2 infections among a prospective cohort of HIV-1-discordant couples in China

ObjectivesIdentification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV-1 transmission, particularly among HIV-1-discordant couples.MethodsA prospective cohort study was...

Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda.

The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but findings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15-49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09-4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49-26·3; p=0·012). Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa. Bill and Melinda Gates Foundation, Doris Duke Charitable Foundation, US National Institutes of Health, and Fogarty International Center.

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.

Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.

Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown. Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1-infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1-susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission. We randomly assigned 911 HSV-2/HIV-1-serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval, .83-2.20]; P = .22). Among HSV-2-susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2-susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016). Treatment of African HSV-2/HIV-1-infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1-infected persons are needed.

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 cross-sectional seroprevalence and the estimated rate of neonatal infections among a cohort of rural Malawian female adolescents

ObjectiveTo assess herpes simplex virus type 2 (HSV-2) seroprevalence among rural Malawian adolescent women and estimate the number of neonatal herpes infections among infants of these adolescents.MethodsA longitudinal cohort study...

Herpes simplex virus type-2 assay specificity and male circumcision to reduce herpes simplex virus type-2 acquisition

In addition, both the Ugandan and Kenyan trials showed that MC reduced genital ulcer disease by 47%–48% [1, 9]. Since the majority of genital ulcers in both men and women are due to herpes simplex virus type-2 (HSV-2) [10–12], it was hypothesized that MC also reduces HSV-2 acquisition. The Ugandan and South African trials evaluated this hypothesis and reported that MC reduced HSV-2 incidence by 25%–34% [8, 13]. Interestingly, however, Mehta et al did not find similar efficacy in the Kenyan trial in Kisumu [9]. All three trials utilized an enzyme-linked immunosorbent assay (ELISA) manufactured by Kalon Biological to detect incident HSV-2. However, interpretation of this assay to detect HSV-2 seroconversion can be problematic, since the index value to define a positive result may differ from the manufacturer’s recommended cut off based on European and North American populations and HSV-2 viruses [14]. There are multiple reports of high false positive rates among African samples [14–18]. We and others found that a higher index cutoff value is required for optimal sensitivity and specificity [14, 16, 19]. When used according to manufacturer’s instructions (index cutoff value 1.1), the Kalon ELISA had a sensitivity of 95.1% and a specificity of only 87.6% in Uganda compared to Western blot [14], whereas a Kalon index value cutoff of 1.5 resulted in a sensitivity of 91.7% and a specificity of 92.4% [14]. Specificity increased to 97.6% with an index value of 2.5 and 98.4% with an index value of 3.5 [14]. In a validation study among men enrolled in the MC trial in Kisumu, the Kalon ELISA at the recommend manufacturer’s cutoff had low sensitivity (92%) and specificity (79%) [20]. In their analysis, Mehta et al used the manufacturer’s cutoff to evaluate the efficacy of MC to reduce HSV-2 incidence [9], a cutoff which is likely to have reduced specificity and may have biased their results towards the null. Mehta et al noted that “no differences were found between circumcised and uncircumcised men at other cutoff values of 1.5, 2.0, 2.5 3.0 and 3.5 [9].” However, to determine whether improved specificity affected MC efficacy estimates in the Ugandan trial, we assessed HSV-2 seroconverters classified by higher Kalon ELISA index values which maximize specificity and reduce potential false positives. For HSV-2 seroconversion rate and person time calculations, it was assumed that HSV-2 infection occurred at the mid-time point between the last negative and first positive serological tests. Time from enrollment was accumulated to the 24 month follow-up visit or the last available sample visit, and HSV-2 seroconversions were estimated per 100 person-years. Incidence rate ratios (IRRs) and 95% confidence intervals (95%CI) were estimated using Poisson regression. As HSV-2 assay specificity increased, MC efficacy to prevent HSV-2 infection increased, albeit modestly (Table). Thus, the previously reported 25–34% reduction in HSV-2 from the Ugandan and South African trials likely represent conservative estimates. As Meta et al note in the discussion, the lack of an association between male circumcision and reduced incident HSV-2 in the Kenyan trial may be due to poor test performance. The results of the Ugandan and Kenyan trials showing reduced genital ulceration following MC and the results of the Ugandan and South African MC trials showing reduced HSV-2 acquisition appear consistent. The analysis in Table 1 suggests that higher assay specificity further strengthens the observed associations that MC reduces both HSV-2 incidence and genital ulcer disease. Table 1 HSV-2 incidence among men in the intervention group (circumcised) and control group based on Kalon index value.

Incidence of herpes simplex virus type 2 in young reproductive age women in Mysore, India

There are sparse data on herpes simplex virus type 2 (HSV-2) infection in India. HSV-2 is one of the most common sexually transmitted infections and the primary cause of genital ulcer disease worldwide. The aim of this study is to describe the incidence of HSV-2 infection among young reproductive age women in Mysore, India. Between October 2005 and April 2006, 898 women were enrolled into a prospective cohort study in Mysore, India, and followed quarterly for 6 months. An interviewer administered questionnaire was used to collect demographic and social risk factors, and physical examination was conducted for collection of biological specimens to screen for reproductive tract infections at each visit. Serologic testing was conducted for the presence of HSV-2 antibodies using HerpeSelect HSV-2 enzyme-linked immunosorbent assay. Data were analyzed using R. Incidence density rates were calculated using Poisson distributions with person-time of follow-up as denominator. Person-time was calculated as time from enrollment until time of first positive HSV-2 test. There were 107 women with HSV-2 antibodies leaving 700 women with negative results at enrollment. The analysis included 696 out of which, there were 36 HSV-2 seroconversions during the study period. The study cohort accumulated roughly 348 woman-years of follow-up, yielding an HSV-2 acquisition rate of 10.4 cases/100 woman-years. All detected infections were asymptomatic. HSV-2 incidence is moderate in this community sample of young reproductive age monogamous women. More research is needed to establish incidence estimates in different Indian settings.

Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis

Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2-seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months. At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44). In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure. (ClinicalTrials.gov numbers, NCT00425984 and NCT00124878.)

Performance of HerpeSelect and Kalon Assays in Detection of Antibodies to Herpes Simplex Virus Type 2

The performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n = 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history.

Transmission of Herpes Simplex Virus Types 1 and 2 in a Prospective Cohort of HIV‐Negative Gay Men: The Health in Men Study

Despite increasing reports of herpes simplex virus (HSV) type 1 (HSV-1)-associated anogenital herpes, there are very limited data comparing the seroepidemiological profile of and risk factors for HSV-1 and HSV type 2 (HSV-2) infection. Sexual behaviors were examined as risk factors for prevalent and incident HSV-1 and HSV-2 infections in a community-based cohort of 1,427 HIV-negative gay men in Australia. The prevalence of HSV-1 and HSV-2 at baseline was 75% and 23%, respectively. The rate of prevalent infection with HSV-1, as well as the rate of prevalent infection with HSV-2, was much lower in individuals <25 years of age, and each type of infection was associated with a higher number of both male and female sex partners. The median duration of follow-up of the cohort was 2.0 years. Among participants who were susceptible to infection, the incidence rates for HSV-1 and HSV-2 infection were 5.58 and 1.45 cases per 100 person-years, respectively. In multivariate analysis, incident infection with HSV-1 was significantly associated with younger age (P=.027) and reports of frequent insertive oral sex with casual partners (hazard ratio, 3.91 [95% confidence interval, 1.23-12.44]; P=.021). Incident infection with HSV-2 was significantly associated with a variety of anal sex practices with casual partners. Both HSV-1 and HSV-2 were commonly sexually transmitted, and there were more HSV-1 than HSV-2 seroconversions. Public-health strategies targeted against anogenital herpes increasingly need to take into account the importance of HSV-1 infection.

Herpes Simplex Virus Type 2 (HSV-2) Seroprevalence at the Time of HIV-1 Diagnosis and Seroincidence After HIV-1 Diagnosis in an Ethnically Diverse Cohort of HIV-1-Infected Persons

The objective of this study was to determine herpes simplex virus type 2 (HSV-2) seroprevalence at HIV-1 diagnosis and seroincidence > or =1 year after HIV-1 diagnosis. HSV type-specific antibodies were detected by enzyme immunoassay. The cohort comprised 850 adults diagnosed HIV-positive in 1986-2001 and followed for a median of 3 years. HSV-2 seroprevalence was 63% (95% confidence interval [CI], 60-66%) and was associated with female gender, heterosexual risk group, black ethnicity, and older age. HSV-2 seroincidence was 1.8 per 100 person-years (95% CI, 0.8-2.8) and was associated with other sexually transmitted diseases, including human papilloma virus infection (P = 0.005) and gonorrhea (P = 0.05). A diagnosis of genital herpes was made in 21% HSV-2-seropositive persons and was more likely in those who tested HIV-positive before 1997 (adjusted odds ratio, 5.11; 95% CI, 3.28-7.98; P = 0.0001). Results confirm the epidemiologic association between HIV-1 and HSV-2. HSV-2 seroconversion was a marker of high-risk sexual behavior. The likelihood of developing symptoms of genital herpes declined from 1997 onward.

Risk Factors Influencing HIV Infection Incidence in a Rural African Population: A Nested Case‐Control Study

Risk factors influencing the incidence of human immunodeficiency virus (HIV) infection were investigated in a case-control study nested within a community-randomized trial of treatment of syndromic sexually transmitted infections (STIs) in rural Tanzania. Case patients were persons who became HIV positive, and control subjects were randomly selected from among persons who remained HIV negative. For each sex, we obtained adjusted odds ratios (ORs) and population-attributable fractions (PAFs) for biomedical and behavioral factors. We analyzed 92 case patients and 903 control subjects. In both sexes, the incidence of HIV infection was significantly higher in subjects with an HIV-positive spouse than in those with HIV-negative spouse (men: OR, 25.1; women: OR, 34.0). The incidence of HIV infection was significantly higher in those who became positive for herpes simplex virus type 2 (HSV-2) (men: OR, 5.60; women: OR, 4.76) and those who were HSV-2-positive at baseline (men: OR, 3.66; women: OR, 2.88) than in subjects who were HSV-2 negative. In women, living elsewhere (OR, 3.22) and never having given birth (OR, 4.27) were significant risk factors. After adjustment, the incidence of HIV infection was not significantly associated with a history of injections or STIs in either sex. HSV-2 infection was the most important risk factor for HIV infection, which highlights the need for HSV-2 interventions in HIV infection control, and there were particularly strong associations with recent HSV-2 seroconversion. The PAF associated with having an HIV-positive spouse was low, but this is likely to increase during the epidemic.

Genital Tract Shedding of Herpes Simplex Virus Type 2 in Women: Effects of Hormonal Contraception, Bacterial Vaginosis, and Vaginal Group B Streptococcus Colonization

Genital infections due to herpes simplex virus type 2 (HSV-2) are characterized by frequent reactivation and shedding of the virus and by the attendant risk of transmission to sexual partners. We investigated the effects of vaginal coinfections and hormonal contraceptive use on genital tract shedding of HSV-2 in women. A total of 330 HSV-2-seropositive women were followed every 4 months for a year. At each visit, one vaginal swab specimen was obtained for detection of HSV-2 by polymerase chain reaction, a second vaginal swab specimen was obtained for detection of group B Streptococcus (GBS) organisms and yeast by culture, and a vaginal smear was obtained for the diagnosis of bacterial vaginosis by Gram staining. HSV-2 DNA was detected in 88 (9%) of 956 vaginal swab specimens. Independent predictors of genital tract shedding of HSV-2 were HSV-2 seroconversion during the previous 4 months (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-6.8), bacterial vaginosis (aOR, 2.3; 95% CI, 1.3-4.0), high-density vaginal GBS colonization (aOR, 2.2; 95% CI, 1.3-3.8), and use of hormonal contraceptives (aOR, 1.8; 95% CI, 1.1-2.8). The present study identifies hormonal contraceptive use, bacterial vaginosis, and high-density vaginal GBS colonization as risk factors for genital tract shedding of HSV-2 in women. Because hormonal contraceptives are used by millions of women worldwide and because bacterial vaginosis and vaginal GBS colonization are common vaginal conditions, even modest associations with HSV-2 shedding would result in substantial attributable risks for transmission of the virus.

Transmission of herpes simplex virus Type 2 among factory workers in Ethiopia.

The herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) epidemics are believed to fuel each other, especially in sub-Saharan countries. In Ethiopia during 1997-2002, a retrospective study was conducted to examine risk factors for infection and transmission of HSV-2, in a cohort of 1612 factory workers. Prevalence of HSV-2 seropositivity at enrollment was 40.9%, and incidence of seroconversion was 1.8 seroconversions/100 person-years (PY), which decreased over time. Independent risk factors for seropositivity were having an HSV-2-seropositive partner, female sex, HIV antibodies, positive Treponema pallidum particle agglutination assay result, older age, low education level, and orthodox religion. These same factors were independent risk factors for HSV-2 seroconversion, with the exception of the latter 3. Most HSV-2-infected persons did not report symptoms. Among 41 monogamous HSV-2-serodiscordant heterosexual couples, incidence of HSV-2 seroconversion was 20.75 seroconversions/100 PY for women and 4.93 seroconversions/100 PY for men. The high burden of both HSV-2 and HIV infection in Ethiopia warrants stringent control measures.