Nicola Low

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

Objectives:To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART). Design:Systematic review and meta-analysis. Methods:We searched Medline, Embase and conference abstracts from 1996–2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit. Results:We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19–1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02–1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. Conclusion:Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting.

Background Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis. Methods and Findings WHO’s 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15–49 years, the estimated global prevalence of chlamydia was 4.2% (95% uncertainty interval (UI): 3.7–4.7%), gonorrhoea 0.8% (0.6–1.0%), trichomoniasis 5.0% (4.0–6.4%), and syphilis 0.5% (0.4–0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0–3.6%), gonorrhoea 0.6% (0.4–0.9%), trichomoniasis 0.6% (0.4–0.8%), and syphilis 0.48% (0.3–0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100–166 million), 78 million of gonorrhoea (53–110 million), 143 million of trichomoniasis (98–202 million), and 6 million of syphilis (4–8 million). Prevalence and incidence estimates varied by region and sex. Conclusions Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.

Risk of sequelae after Chlamydia trachomatis genital infection in women.

Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.

Global control of sexually transmitted infections

Sexually transmitted infections other than HIV are important global health issues. They have, however, been neglected as a public-health priority and control efforts continue to fail. Sexually transmitted infections, by their nature, affect individuals, who are part of partnerships and larger sexual networks, and in turn populations. We propose a framework of individual, partnership, and population levels for examining the effects of sexually transmitted infections and interventions to control them. At the individual level we have a range of effective diagnostic tests, treatments, and vaccines. These options are unavailable or inaccessible in many resource-poor settings, where syndromic management remains the core intervention for individual case management. At the partnership level, partner notification and antenatal syphilis screening have the potential to prevent infection and re-infection. Interventions delivered to whole populations, or groups in whom the risks of infection and onward transmission are very high, have the greatest potential effect. Improvements to the infrastructure of treatment services can reduce the incidence of syphilis and gonorrhoea or urethritis. Strong evidence for the effectiveness of most other interventions on population-level outcomes is, however, scarce. Effective action requires a multifaceted approach including better basic epidemiological and surveillance data, high quality evidence about effectiveness of individual interventions and programmes, better methods to get effective interventions onto the policy agenda, and better advocacy and more commitment to get them implemented properly. We must not allow stigma, prejudice, and moral opposition to obstruct the goals of infectious disease control.

Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis

Abstract Objectives: To analyse trends in rates of genital chlamydial infection and ectopic pregnancy between 1985 and 1995 in a county in Sweden. Setting: Uppsala county where screening for chlamydial infection, treatment, and contact tracing has been widespread and where ectopic pregnancies are recorded. Methods: Rates of chlamydial infections and ectopic pregnancy between 1985 and 1995 were calculated for women aged 20-39 years. Poisson and linear regression were used to examine the association between the risk of ectopic pregnancy and the current rates of chlamydial infection and rates of chlamydial infection from up to 5 years earlier. Main outcome measures: Rates of chlamydial infection per 100 examinations, rates of ectopic pregnancy per 1000 pregnancies, rate ratios and 95% confidence intervals for an increase in chlamydial infections of 5 new cases per 100 examinations. Results: 103 870 cervical samples from women aged 15-39 years were analysed; 5648 (5.4%) were positive for chlamydia. 51 630 pregnancies were analysed; 930 (1.8%) were ectopic. Both rates declined over time. For women aged 20-24 years there was a strong correlation between the rate of ectopic pregnancy and the rate of chlamydial infection in the same year (r=0.93, P<0.001); among older women correlations were stronger with rates of chlamydial infection occurring 1 or 2 years earlier. In Poisson regression ectopic pregnancy was most strongly associated with the current rate of chlamydial infection among women aged 20-24 (rate ratio 1.85, 95% confidence interval 1.44 to 2.38), with the rate of infection 1 year earlier among 25-29 year olds (rate ratio 1.72, 1.33 to 2.22) and 30-34 year olds (rate ratio 2.27, 1.53 to 3.37); and with the rate 2 years earlier among 35 to 39 year olds (rate ratio 2.58, 1.45 to 4.60). Conclusions: Declining rates of genital chlamydial infections have probably led to a fall in the rate of ectopic pregnancies. The timing of the decline in the rate of ectopic pregnancies varies with age. Among young women falling rates of chlamydial infection have been accompanied by an immediate reduction in the rate of ectopic pregnancy. Key messages The effect of measures to diagnose and treat genital chlamydial infections on the risk of ectopic pregnancy was examined in a county in Sweden Rates of chlamydial infection and ectopic pregnancy both declined between 1985 and 1995 Chlamydial infections seem to be the main cause of ectopic pregnancy in young women; the risk of ectopic pregnancy decreased concurrently with the decline in chlamydial infections In older women the associations were less pronounced

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration.

AIMS To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Improved effectiveness of partner notification for patients with sexually transmitted infections: systematic review

Objective To examine the effectiveness of methods to improve partner notification by patient referral (index patient has responsibility for informing sex partners of their exposure to a sexually transmitted infection). Design Systematic review of randomised trials of any intervention to supplement simple patient referral. Data sources Seven electronic databases searched (January 1990 to December 2005) without language restriction, and reference lists of retrieved articles. Review methods Selection of trials, data extraction, and quality assessment were done by two independent reviewers. The primary outcome was a reduction of incidence or prevalence of sexually transmitted infections in index patients. If this was not reported data were extracted according to a hierarchy of secondary outcomes: number of partners treated; number of partners tested or testing positive; and number of partners notified, located, or elicited. Random effects meta-analysis was carried out when appropriate. Results 14 trials were included with 12 389 women and men diagnosed as having gonorrhoea, chlamydia, non-gonococcal urethritis, trichomoniasis, or a sexually transmitted infection syndrome. All studies had methodological weaknesses that could have biased their results. Three strategies were used. Six trials examined patient delivered partner therapy. Meta-analysis of five of these showed a reduced risk of persistent or recurrent infection in patients with chlamydia or gonorrhoea (summary risk ratio 0.73, 95% confidence interval 0.57 to 0.93). Supplementing patient referral with information for partners was as effective as patient delivered partner therapy. Neither strategy was effective in women with trichomoniasis. Two trials found that providing index patients with chlamydia with sampling kits for their partners increased the number of partners who got treated. Conclusions Involving index patients in shared responsibility for the management of sexual partners improves outcomes. Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners.

HIV and male circumcision--a systematic review with assessment of the quality of studies.

This Cochrane systematic review assesses the evidence for an interventional effect of male circumcision in preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse. The review includes a comprehensive assessment of the quality of all 37 included observational studies. Studies in high-risk populations consisted of four cohort studies, 12 cross-sectional studies, and three case-control studies; general population studies consisted of one cohort study, 16 cross-sectional studies, and one case-control study. There is evidence of methodological heterogeneity between studies, and statistical heterogeneity was highly significant for both general population cross-sectional studies (chi(2)=132.34; degrees of freedom [df]=15; p<0.00001) and high-risk cross-sectional studies (chi(2)=29.70; df=10; p=0.001). Study quality was very variable and no studies measured the same set of potential confounding variables. Therefore, conducting a meta-analysis was inappropriate. Detailed quality assessment of observational studies can provide a useful visual aid to interpreting findings. Although most studies show an association between male circumcision and prevention of HIV, these results may be limited by confounding, which is unlikely to be adjusted for.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.