Effect of Vaginal Microecological Disorders on the Increased Risk of Abnormal Cervical Cytology Among Women With Human Immunodeficiency Virus in China.

BACKGROUND: Abnormal cervical cytology is commonly observed in women with human immunodeficiency virus (WWH). METHODS: A cross-sectional study was conducted with 130 WWH and 147 age-matched healthy controls, who underwent gynecological examinations at Beijing Ditan Hospital. The presence of abnormal cervical cytology in WWH was predicted after performing a logistic regression analysis. RESULTS: Multivariate logistic regression revealed 3 independent factors, among which CD4 cell count ≥350 cells/µL was the protective factor, while human papillomavirus infection and abnormal vaginal pH were the risk factors. CONCLUSIONS: Vaginal microecological disorders can increase the risk of abnormal cervical cytology in WWH.

Society for Maternal-Fetal Medicine Special Statement: Reducing the risk of transmitting infection by transvaginal ultrasound examination.

Recent surveys have shown widespread lapses in the procedures used to reduce the risk of transmitting infection via medical devices. Transvaginal ultrasound examination has the potential to transmit vaginal infections, including human papillomavirus. Areas of particular concern are the use of probe covers with high rates of leakage, disinfectants that are not effective against human papillomavirus, and coupling gel from multiple-use containers. We reviewed these issues, and we recommend 4 steps to reduce the risk of transmitting infection. First, during every transvaginal ultrasound exam, the probe should be covered with a sterile, single-use "viral barrier" cover or a condom. Second, sterile, single-use ultrasound gel packets should be used. Third, after every examination, the probe should be cleaned to remove any visible gel or debris. Finally, after cleaning, the probe should undergo high-level disinfection using an agent with proven efficacy against the human papillomavirus, including hydrogen peroxide, hypochlorite, or peracetic acid. Glutaraldehyde, orthophthalaldehyde, phenols, and isopropyl alcohol have virtually no efficacy against the human papillomavirus.

Time-trend of hospitalizations for anogenital warts in Veneto region in the HPV vaccination era: a cross sectional study (2007-2018).

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted pathogen and the cause of several cancers and of anogenital warts. With this study, we estimated the trend of hospitalizations for anogenital warts (AGWs) in the Veneto region (Italy) from 2007 to 2018. METHODS: The analysis included all the hospital discharge records of public and accredited private hospitals occurred in Veneto residents in the timespan 2007-2018. The ICD9-CM code 078.11 considered were those associated with condyloma acuminatum and those associated with surgical interventions for vulval/vaginal warts, penile warts anal warts. Annual total and sex- and age-specific hospitalization rates and trends were calculated and correlated with the different HPV vaccine coverage over the study period. RESULTS: We observed an overall reduction of hospitalization rates for AGWs: from 15.0 hospitalizations every 100,000 Veneto residents in years 2007-08 to 10.9 hospitalizations every 100,000 Veneto residents in year 2017-18 (- 37.4%; p < 0.05). Reduction has been caused by a drop in hospitalizations in females - from a rate of 20.4/100,000 in 2007-2008 to a rate of 10.8/100,000 in 2017-18 (AAPC: -7.1; 95%CI: - 10.6;-3.4); while in males, we observed a slight - but not statistically significant - increase in hospitalization rates. CONCLUSION: The marked decline in hospitalization rates for AGWs in Veneto Region is probably attributable to the high coverage rates of HPV vaccination programs implemented since 2008.

Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population.

OBJECTIVE: Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured for the five HPV types covered only by 9vHPV vaccine (HPV31/33/45/52/58), but not the four types covered by both vaccines (HPV6/11/16/18). METHODS: Three international, randomized, double-blind studies were conducted using the same methodology. In the 9vHPV vaccine study (NCT00543543), 7106 and 7109 women received 9vHPV or qHPV vaccine, respectively. In the historic qHPV vaccine studies (FUTURE I [NCT00092521] and II [NCT00092534]), 8810 and 8812 women received qHPV vaccine or placebo, respectively, based on the same eligibility criteria. Cervical cytological testing was performed regularly. Biopsy or definitive therapy specimens were assessed for HPV DNA. RESULTS: Among women negative for 14 HPV types prior to vaccination, incidence of high-grade cervical disease (9vHPV, n = 2 cases; placebo, n = 141 cases) and cervical surgery (9vHPV, n = 3 cases; placebo, n = 170 cases) related to the nine HPV types was reduced by 98.2% (95% confidence interval [CI], 93.6-99.7) and 97.8% (95% CI, 93.4-99.4), respectively. The 9vHPV vaccine did not prevent disease related to vaccine HPV types detected at baseline, but significantly reduced cervical, vulvar, and vaginal diseases related to other vaccine HPV types. CONCLUSIONS: Effective implementation of the 9vHPV vaccine may substantially reduce the burden of HPV-related diseases and related medical procedures. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00543543, NCT00092521, NCT00092534.

Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian population.

OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within the context of the country's sociodemographic attributes. The objective of this study is to determine the prevalence of cervicovaginal HPV infection among a healthy, community-based, multiethnic Malaysian population. The HPV prevalence was subsequently correlated to the individual's sociodemographics and sexual/reproductive history. Of significance, the observed prevalence captured was in a birth cohort not included in the national school-based HPV vaccination programme. METHODS: This was a cross-sectional study where 1293 healthy women aged between 18 and 60 years were recruited via convenience sampling from five community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were obtained and DNA was extracted for HPV detection and genotyping. A comprehensive questionnaire was administered to determine the sociodemographics and behavioural patterns of participants. RESULTS: The median age at enrolment was 37 years old (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52 and 58. The independent risk factors associated with higher rates of HPV infection included Indian ethnicity, widowed status and women with partners who are away from home for long periods and/or has another sexual partner. CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top three most common high-risk HPV types were HPV 16, 52 and 58. This information is important for the planning of primary (HPV vaccination) and secondary (screening) cervical cancer prevention programmes in Malaysia.

Influence of co-infection complicated with human papillomavirus on cervical intraepithelial neoplasia development in patients with atypical squamous cells of undetermined significance.

AIM: Human papillomaviruses (HPV) infection is a primary cause of the development of cervical precancerous lesions and cervical cancer. However, the influence of other infections on intraepithelial neoplasia (CIN) development has not been fully elucidated. We evaluated the association between co-infection and CIN development in subjects with atypical squamous cells of undetermined significance (ASCUS). METHOD: Data for ASCUS subjects who had undergone testing for high risk HPV (HR-HPV) and pathological diagnosis were analyzed. From the CIN grade, HR-HPV and vaginal infection (VI) data, both the relationship between HPV infection and CIN development and the influence of co-infection on CIN were retrospectively evaluated. RESULTS: Data for 56 ASCUS subjects who had undergone HR-HPV testing and cytological diagnosis were analyzed. Positive rates were HPV (73.2%), HPV16 (21.4%), HPV18 (7.1%), and HPV16 and/or 18 (26.8%). Seventeen of the subjects were diagnosed as having one or more VI pathogen; the major pathogens found were Candida spp., Gardnerella vaginalis, group B streptococcus, coagulase negative Staphylococcus, and Chlamydia trachomatis. The rate of CIN 2 or worse (≥CIN 2) was significantly higher in subjects positive for HPV16 compared with HPV negative subjects, and was significantly higher in subjects with a VI complicated with HPV compared to those without a VI. Univariate and multivariate logistic regression analysis identified positive for HPV16 and/or 18 and positive for VI to be significant variables for ≥ CIN 2. CONCLUSION: Our results indicate that having a vaginal infection complicated with HR-HPV affects the development of CIN in subjects with ASCUS cytology.

The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature.

BACKGROUND: Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. METHODS: A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. RESULTS: Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. CONCLUSIONS: Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy. TRIAL REGISTRATION: Not applicable, as systematic review of the literature.

Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV.

Vaginal microbiota and sexually transmitted infections (STIs) are likely to influence the transmission of cell-associated human immunodeficiency virus (HIV). Lactic acid produced by Lactobacillus-dominated microbiota (Nugent score 0-3) will likely inhibit transmission, especially female-to-male transmission. In contrast, polymicrobial microbiota (Nugent score 4-10), community state types IV-A and IV-B, and STIs will likely increase transmission of cell-associated HIV.

Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection.

IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)-specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases.

Incidence of genital warts in adolescents and young adults in an integrated health care delivery system in the United States before human papillomavirus vaccine recommendations.

BACKGROUND: Information on genital wart incidence in adolescents and young adults before human papillomavirus (HPV) vaccination is important for understanding the impact of the vaccine on the epidemiology of this early outcome of HPV infection. METHODS: The study population included 11- to 29-year-old enrollees of Northern California Kaiser Permanente between July 1, 2000, and July 1, 2005, before the availability of the HPV vaccine. We identified genital warts with an algorithm combining genital wart-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes (078.10, 078.11, and 078.19) with physician-recorded anatomic locations. We calculated sex- and age-specific incidence rates of genital warts and described the specific anatomic location of presentation, as well as recurrences of genital warts. RESULTS: We identified 1,682 cases of genital warts among 181,264 individuals. The incidence rate was highest among women (6.3/1000 person-years) and men (2.9/1000 person-years) aged 20 to 24 years old. Among women (n = 96,792), 63.4% of the 1240 incident genital wart cases occurred on the vulva and 21.1% on the cervix. Among men (n = 84,472), 91.6% of the 442 incident genital wart cases did not have a specific anatomic location recorded. Most people with an incident genital wart diagnosis (87.2%) did not have a recurrence during the observation period. CONCLUSIONS: Our study found that the incidence of genital warts was highest among persons aged 20 to 24 years using a unique method to identify the location of the wart. Information on incidence of genital warts before vaccine use provides baseline data that can be used to measure HPV vaccine impact.

Role of next-generation sequencing in understanding the interactions between human papillomavirus and the cervicovaginal microbiome.

The applications of next-generation sequencing in the field of human papillomavirus and associated neoplasias have extended beyond the accurate genotyping of human papillomavirus types. Next-generation sequencing is able to provide important information on the interactions of the cervicovaginal microbiome and environment with the virus, and the role that these factors play on its transmission and persistence. The advances in sequencing technologies have greatly contributed to the current knowledge of human cervicovaginal microbiome in recent years, allowing the assessment of microbiome variability between species, individuals and populations.

Genital ulceration does not increase HIV-1 shedding in cervical or vaginal secretions of women taking antiretroviral therapy.

OBJECTIVES: Genital ulcer disease (GUD) is associated with increased HIV-1-RNA shedding in antiretroviral therapy (ART)-naive women. The effect of GUD on HIV-1 shedding among ART-treated women is not known. The objective of this study was to test the hypothesis that genital ulcerations increase genital HIV-1-RNA shedding in women receiving ART. METHODS: Eligible women initiated ART and attended monthly visits with inspection for genital lesions and collection of genital swabs. GUD cases diagnosed after 2 months or more on ART were included for analysis and served as their own controls. HIV-1 RNA was quantitated in specimens collected before, during and after GUD for all cases. The lower limit of quantitation was 100 HIV-1-RNA copies/swab. Using the pre-GUD visit as the reference, the detection of genital HIV-1 RNA before versus during and after GUD episodes was compared. RESULTS: 36 women had GUD episodes after ART initiation. HIV-1 RNA was detected before, during and after GUD in cervical secretions from four (11%), one (3%) and six (17%) women, respectively, and in vaginal secretions from three (8%), four (11%) and four (11%) women, respectively. After adjustment for time on ART, there was no difference in the detection of cervical HIV-1 RNA before versus during GUD (adjusted OR 0.22, 95% CI 0.04 to 1.23). Likewise, GUD did not increase HIV-1 detection in vaginal secretions (adjusted OR 1.32, 95% CI 0.29 to 5.92). CONCLUSIONS: GUD did not significantly increase cervical or vaginal HIV-1 shedding. The results suggest that ART maintains its effectiveness for genital HIV-1 suppression despite GUD episodes.

High squamous intraepithelial lesion and cancer of lower genital tract in women with anogenital warts.

PURPOSE: The aim of this paper was to determine the incidence of high-grade squamous intraepithelial lesion (HSIL) and cancer of lower genital tract in patients with anogenital warts and their treatment. METHODS: Between 1 September 1988 and 30 June 1994, 221 consecutive women with anogenital warts were prospectively examined in the colposcopy outpatient clinic. In 2004, the same group of patients was re-examined. RESULTS: There were abnormal cytological findings in 111 (50.2%) patients; 31 patients (14.0%) had HSIL, and 6 of them (2.7%) had cancer. There were abnormal colposcopic findings in 152 (68.8%) women; 78 women (35.3%) had abnormal histological findings. In the histological findings, HSIL was found in 41 (18.5%) women and cancer in 6 (2.7%). CONCLUSION: In spite of the fact that anogenital warts are caused by HPV types of low oncogenic risk (6/11), there is an increased incidence of HSIL and cancer in these women. Therefore, women with anogenital warts belong to an increased risk group regarding the cancer of lower genital tract, especially if they are associated with HPV types of a high oncogenic risk.

Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor.

An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small-molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected individuals, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide with use of a stringent model that involves challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/mL). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (half life of approximately 4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated postinfection viremia. These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth.

Importance: Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. Objective: To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. Design, Setting, and Participants: The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Exposures: Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. Main Outcomes and Measures: The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. Results: The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. Conclusions and Relevance: The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection.

How helminths influence the pathogenesis of sexually transmitted viral infections is not comprehensively understood. Here, we show that an acute helminth infection (Nippostrongylus brasiliensis [Nb]) induced a type 2 immune profile in the female genital tract (FGT). This leads to heightened epithelial ulceration and pathology in subsequent herpes simplex virus (HSV)-2 infection. This was IL-5-dependent but IL-4 receptor alpha (Il4ra) independent, associated with increased FGT eosinophils, raised vaginal IL-33, and enhanced epithelial necrosis. Vaginal eosinophil accumulation was promoted by IL-33 induction following targeted vaginal epithelium damage from a papain challenge. Inhibition of IL-33 protected against Nb-exacerbated HSV-2 pathology. Eosinophil depletion reduced IL-33 release and HSV-2 ulceration in Nb-infected mice. These findings demonstrate that Nb-initiated FGT eosinophil recruitment promotes an eosinophil, IL-33, and IL-5 inflammatory circuit that enhances vaginal epithelial necrosis and pathology following HSV-2 infection. These findings identify a mechanistic framework as to how helminth infections can exacerbate viral-induced vaginal pathology.

Nonfatal clinical presentation of elephant endotheliotropic herpes virus discovered in a group of captive Asian elephants (Elephas maximus).

Several different strains of elephant endotheliotropic herpes virus-1 (EEHV-1) have been identified via polymerase chain reaction (PCR) techniques in both African and Asian elephants. EEHV-1 has been identified in both cutaneous lesions in healthy African elephants and fatal cases of hemorrhagic syndrome in Asian elephants. However, until now, no EEHV-1 strain has been identified or associated with otherwise healthy Asian elephants. This article describes recurrent nonendothelial lesions associated with EEHV-1 infection in a herd of Asian elephants not exhibiting fatal hemorrhagic syndrome. Genotypes of EEHV-1 strains, based on viral DNA polymerase and glycoprotein B, associated with fatal hemorrhagic syndrome, were compared to those identified in nonendothelial lesions. The same EEHV-1 genotypes were identified in fatal cases and mucosal lesions in otherwise healthy Asian elephants in this herd. Further studies of the Asian elephant immune system and virologic studies to determine the triggers of tissue tropism are needed before any conclusion can be reached. Elephant endotheliotropic herpes virus, EEHV, herpetic lesions, tropism.

Feasibility, Acceptability, and Accuracy of Vaginal Self-Sampling for Screening Human Papillomavirus Types in Women from Rural Areas in Senegal.

Vaginal self-sampling and human papillomavirus (HPV) DNA testing can be useful tools for women with limited access to health care living in sub-Saharan Africa. To assess the feasibility and acceptability of vaginal self-sampling and high-risk HPV prevalence in two villages of central Senegal, women were asked to self-sample vaginal swabs for HPV detection in May, 2016. Vaginal swabs were collected from 133 women and were tested for HPV genotyping. The acceptability rate of vaginal self-sampling was 98.5%, and 99.2% of the women (133/134) used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 10.5% of the samples were positive for HPV, including 6% with high-risk HPV types and 4% with low-risk HPV types. This preliminary study indicates that vaginal self-sampling is a valuable strategy for high-risk HPV detection and cervical cancer screening in a population of women not attending gynecologic screening in rural areas of Senegal.

Effect of HIV-1 and antiretroviral therapy on herpes simplex virus type 2: a prospective study in African women.

OBJECTIVES: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso. METHODS: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrollment. RESULTS: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/microl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200-500 cells/microl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86). CONCLUSIONS: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.