Helen A. Weiss

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

Objective:To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. Background:The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. Design:Systematic review and meta-analysis of longitudinal studies. Methods:PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. Results:Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9–3.9] and women (RR, 3.1; 95% CI, 1.7–5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2–2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. Conclusions:Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis.

ObjectiveTo systematically review studies of male circumcision and the risk of HIV-1 infection in men in sub-Saharan Africa, and to summarize the findings in a meta-analysis. DesignA meta-analysis of observational studies. MethodsA systematic literature review was carried out of studies published up to April 1999 that included circumcision as a risk factor for HIV-1 infection among men in sub-Saharan Africa. A random effects meta-analysis was used to calculate a pooled relative risk (RR) and 95% confidence interval (CI) for all studies combined, and stratified by type of study population. Further analyses were conducted among those studies that adjusted for potential confounding factors. ResultsTwenty-seven studies were included. Of these, 21 showed a reduced risk of HIV among circumcised men, being approximately half that in uncircumcised men (crude RR = 0.52, CI 0.40–0.68). In 15 studies that adjusted for potential confounding factors, the association was even stronger (adjusted RR = 0.42, CI 0.34–0.54). The association was stronger among men at high risk of HIV (crude RR = 0.27; adjusted RR = 0.29, CI 0.20–0.41) than among men in general populations (crude RR = 0.93; adjusted RR = 0.56, CI 0.44–0.70). ConclusionMale circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised.

Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania

BACKGROUND Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition. METHODS Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit. RESULTS A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir. CONCLUSIONS These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.

Objectives: Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Haemophilus ducreyi. Methods: Electronic databases (1950–2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. Results: 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV-2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). Conclusions: This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV-2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI.

Effectiveness of an intervention led by lay health counsellors for depressive and anxiety disorders in primary care in Goa, India (MANAS): a cluster randomised controlled trial.

: Depression and anxiety disorders are common mental disorders worldwide. The MANAS trial aimed to test the effectiveness of an intervention led by lay health counsellors in primary care settings to improve outcomes of people with these disorders. : In this cluster randomised trial, primary care facilities in Goa, India, were assigned (1:1) by computer-generated randomised sequence to intervention or control (enhanced usual care) groups. All adults who screened positive for common mental disorders were eligible. The collaborative stepped-care intervention offered case management and psychosocial interventions, provided by a trained lay health counsellor, supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist. The research assessor was masked. The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision (ICD-10) at 6 months. This study is registered with ClinicalTrials.gov, number NCT00446407. : 24 study clusters, with an equal proportion of public and private facilities, were randomised equally between groups. 1160 of 1360 (85%) patients in the intervention group and 1269 of 1436 (88%) in the control group completed the outcome assessment. Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group (n=620 [65·0%] vs 553 [52·9%]; risk ratio 1·22, 95% CI 1·00-1·47; risk difference=12·1%, 95% CI 1·6%-22·5%). The intervention had strong evidence of an effect in public facility attenders (369 [65·9%] vs 267 [42·5%], risk ratio 1·55, 95% CI 1·02-2·35) but no evidence for an effect in private facility attenders (251 [64·1%] vs 286 [65·9%], risk ratio 0·95, 0·74-1·22). There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group. None of the deaths were from suicide. : A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities. : The Wellcome Trust.BACKGROUND Depression and anxiety disorders are common mental disorders worldwide. The MANAS trial aimed to test the effectiveness of an intervention led by lay health counsellors in primary care settings to improve outcomes of people with these disorders. METHODS In this cluster randomised trial, primary care facilities in Goa, India, were assigned (1:1) by computer-generated randomised sequence to intervention or control (enhanced usual care) groups. All adults who screened positive for common mental disorders were eligible. The collaborative stepped-care intervention offered case management and psychosocial interventions, provided by a trained lay health counsellor, supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist. The research assessor was masked. The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision (ICD-10) at 6 months. This study is registered with ClinicalTrials.gov, number NCT00446407. FINDINGS 24 study clusters, with an equal proportion of public and private facilities, were randomised equally between groups. 1160 of 1360 (85%) patients in the intervention group and 1269 of 1436 (88%) in the control group completed the outcome assessment. Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group (n=620 [65·0%] vs 553 [52·9%]; risk ratio 1·22, 95% CI 1·00-1·47; risk difference=12·1%, 95% CI 1·6%-22·5%). The intervention had strong evidence of an effect in public facility attenders (369 [65·9%] vs 267 [42·5%], risk ratio 1·55, 95% CI 1·02-2·35) but no evidence for an effect in private facility attenders (251 [64·1%] vs 286 [65·9%], risk ratio 0·95, 0·74-1·22). There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group. None of the deaths were from suicide. INTERPRETATION A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities. FUNDING The Wellcome Trust.

Interactions between Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Type 1 Infection in African Women: Opportunities for Intervention

Sexually transmitted diseases (STDs) are cofactors for human immunodeficiency virus (HIV) transmission, but the specific role of herpes simplex virus type 2 (HSV-2) is unclear. This study aimed to examine the in vivo relationships between HSV-2 and HIV-1 in 300 women in Bangui, Central African Republic. Sera were tested for syphilis, HIV-1, HSV-2 antibody, and levels of vitamins A and E. Genital specimens were tested for other STDs. HSV-2 DNA and HIV-1 RNA were quantified in cervicovaginal lavage. The prevalences of HSV-2 antibody (91% vs. 78%, P=.02), HSV-2 shedding (43% vs. 22%, P=. 003), and levels of HSV-2 DNA (P=.01) were all significantly higher among HIV-1-seropositive than among HIV-1-seronegative women. There was a significant correlation between genital HIV-1 RNA and HSV-2 DNA levels (P=.02) among the 23 women who were shedding HSV-2 DNA. If confirmed, such associations highlight the urgent need for HSV-2 control measures in populations at high risk of both infections.

Biological and behavioural impact of an adolescent sexual health intervention in Tanzania : a community-randomized trial

Objective:The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania. Design:A community-randomized trial. Methods:Twenty communities were randomly allocated to receive either a specially designed programme of interventions (intervention group) or standard activities (comparison group). The intervention had four components: community activities; teacher-led, peer-assisted sexual health education in years 5–7 of primary school; training and supervision of health workers to provide ‘youth-friendly’ sexual health services; and peer condom social marketing. Impacts on HIV incidence, herpes simplex virus 2 (HSV2) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5, 6 or 7 of primary school. Results:The intervention had a significant impact on knowledge and reported attitudes, reported sexually transmitted infection symptoms, and several behavioural outcomes. Only five HIV seroconversions occurred in boys, whereas in girls the adjusted rate ratio (intervention versus comparison) was 0.75 [95% confidence interval (CI) 0.34, 1.66]. Overall HSV2 prevalences at follow-up were 11.9% in male and 21.1% in female participants, with adjusted prevalence ratios of 0.92 (CI 0.69, 1.22) and 1.05 (CI 0.83, 1.32), respectively. There was no consistent beneficial or adverse impact on other biological outcomes. The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002. Conclusion:The intervention substantially improved knowledge, reported attitudes and some reported sexual behaviours, especially in boys, but had no consistent impact on biological outcomes within the 3-year trial period.

Detecting common mental disorders in primary care in India: a comparison of five screening questionnaires

BACKGROUND Screening of patients for common mental disorders (CMDs) is needed in primary-care management programmes. This study aimed to compare the screening properties of five widely used questionnaires. METHOD Adult attenders in five primary-care settings in India were recruited through systematic sampling. Four questionnaires were administered, in pairs, in random order to participants: the General Health Questionnaire (GHQ, 12 items); the Primary Health Questionnaire (PHQ, nine items); the Kessler Psychological Distress Scale (K10, 10 items), and from which we could extract the score of the shorter 6-item K6; and the Self-Reporting Questionnaire (SRQ, 20 items). All participants were interviewed with a structured lay diagnostic interview, the Revised Clinical Interview Schedule (CIS-R). RESULTS Complete data were available for 598 participants (participation rate 99.3%). All five questionnaires showed moderate to high discriminating ability; the GHQ and SRQ showed the best results. All five showed moderate to high degrees of correlation with one another, the poorest being between the two shortest questionnaires, K6 and PHQ. All five had relatively good internal consistency. However, the positive predictive value (PPV) of the questionnaires compared with the diagnostic interview ranged from 51% to 77% at the optimal cut-off scores. CONCLUSIONS There is little difference in the ability of these questionnaires to identify cases accurately, but none showed high PPVs without a considerable compromise on sensitivity. Hence, the choice of an optimum cut-off score that yields the best balance between sensitivity and PPV may need to be tailored to individual settings, with a higher cut-off being recommended in resource-limited primary-care settings.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

Objectives: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Design and methods: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. Results: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. Conclusions: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Male circumcision for HIV prevention: from evidence to action?

An estimated 2.5 million people were newly infected with HIV in 2007 of whom two-thirds live in sub-Saharan Africa. In the context of the urgent need for intensified and expanded HIV prevention efforts the conclusive results of three randomized controlled trials (RCT) showing that male circumcision reduces the risk of HIV-acquisition by approximately 60% are both promising and challenging. Translation of these research findings into public health policy is complex and will be context specific. To guide this translation we estimate the global prevalence and distribution of male circumcision summarize the evidence of an impact on HIV incidence and highlight the major public health opportunities and challenges raised by these findings. (excerpt)