Diagnosis and Treatment of Sexually Transmitted Infections
I. Definition of the Prevention Area
Sexually transmitted infections (STIs) likely facilitate HIV transmission and acquisition. STI treatment efforts have been used as an HIV prevention approach with mixed outcomes. This prevention strategy may be most effective in settings with a high burden of STIs and when targeted to most-at-risk populations and their sexual partners. However, randomized trials have found STI treatment to have little to no effect on HIV incidence.
II. Epidemiological Justification for the Prevention Area
The role of STIs in the transmission dynamics of HIV epidemics is paradoxical and complex. Population-based studies have found that both the prevalence and incidence of HIV were substantially higher in people with STIs. Both curable STIs and chronic infections such as herpes simplex virus type-2 (genital herpes) can increase vulnerability to HIV infection by disrupting skin and mucosal barriers and/or by causing inflammation that brings HIV-susceptible immune cells to the genital tract. STIs are biological markers for risky sexual behaviors, which are also risk factors for HIV acquisition.
In addition, a number of studies in HIV serodiscordant couples report that HIV-positive individuals with herpes or genital ulcer disease are significantly more likely to transmit HIV to their partners. Some STIs appear to increase the risk of HIV transmission by boosting viral shedding in the genital secretions of both men and women who are HIV-positive. Other studies of HIV-positive individuals on antiretroviral therapy suggest that STIs may increase the infectiousness of HIV, even when an individual has an undetectable viral load.
Despite these data, numerous clinical trials have not been able to demonstrate a decline in HIV incidence as a result of STI treatment. Some hypothesize that treated STIs may still cause inflammation and other changes in the genital mucosa even after the initial symptoms have disappeared. The ongoing inflammation and changes in the genital mucosa may be why STI treatment does not have an effect on HIV incidence. Epidemic stage, prevalence of viral versus bacterial STIs, and type of treatment may also be reasons that STI treatment does not lower HIV incidence.
III. Core Programmatic Components
While STI treatment does not seem to have a significant impact on HIV incidence, effective management of STIs is an essential public health activity and is particularly important for improved maternal and child health outcomes. Data linking the prevalence of STIs with increased risk of HIV transmission and acquisition underscore the importance of STI prevention, which can best be achieved through a comprehensive STI control program.
The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports STI control for HIV prevention depending on epidemic type and population. In concentrated epidemics, the population focus should be on most-at-risk populations, individuals with symptomatic STIs, HIV-positive persons with high-risk behaviors, and other groups that may be at high risk for STI acquisition. In generalized epidemics, PEPFAR supports STI control programs for high-risk subpopulations, including most-at-risk populations, individuals with symptomatic STIs, HIV-positive persons, and sexually active adolescents. PEPFAR also supports HIV testing and counseling services for STI patients.
A 2009 review of STI control and HIV prevention in the Bulletin of the World Health Organization concluded that the core elements of a comprehensive STI control program should include:
- Reaching out to populations at greatest risk, particularly those who change partners frequently, potentially propelling transmission within the population
- Promoting safer sex through the provision of condoms and other prevention activities
- Offering effective clinical interventions (including STI screening, treatment, and case management)
- Initiating structural interventions to ensure an environment that supports safer sex behavior and care- and treatment-seeking behaviors
- Collecting reliable data to monitor disease trends and the effectiveness of interventions.
IV. Current Status of Implementation Experience
Research is ongoing to better understand how STIs modify HIV transmission. The development of improved screening strategies to detect some asymptomatic STIs in resource-limited settings remains a research priority. Currently, STI treatment as a stand-alone HIV prevention intervention in generalized epidemics is not supported by scientific data.
STI control for HIV prevention depends on the type of HIV epidemic and the populations at highest risk. A number of resource-limited countries, including Cambodia, Kenya, Senegal, Sri Lanka, and Thailand, have demonstrated that it is feasible for programs to expand STI control services. Several countries that have successfully controlled STIs have also reported stabilization or reversal of their HIV epidemics. For instance, in India, the Avahan Initiative reported a reduction in STI and HIV incidence after it included the improved delivery of STI management to most-at-risk groups as part of its comprehensive prevention interventions. Thailand's 100% Condom Program appears to have contributed to both STI reduction and HIV prevention by requiring condom use in brothels. STI screening, management, and treatment are key components of the PEPFAR comprehensive package of services for most-at-risk populations.
The review examines the role that sexually transmitted infections (STIs) play in people living with HIV and how the co-infections of STIs and HIV play on the prevention potential of antiretroviral therapy (ART) in limiting HIV transmission rates. The search includes studies that report on STIs in people living with HIV and were published from 2000 to 2010. It also only includes STIs that demonstrate HIV shedding in the genital tract such as syphilis, chancroid, and gonorrhea. Thirty-seven studies are presented in the review, and it was found that the overall mean point prevalence of STI co-infection was 16.3 percent. The most common STIs co-infections were syphilis, gonorrhea, chlamydia, and trichomoniasis. The highest prevalence of STI/HIV co-infections were in people newly diagnosed with HIV, but STI co-infections take place throughout the course of HIV infection and not only when first diagnosed. For example, the average STI/HIV co-infections was 14 percent. People taking ART also were diagnosed with STI co-infections to a high degree, and there was not a significant difference of co-infections between HIV-positive individuals who were or were not on ART. The review points to limitations to forecast data on the overall effect of ART for prevention programs on reducing transmission rates in HIV epidemics. They often do not include the effect of STI co-infections in the models, which would reduce the successfulness of those results. STI co-infections should be included in future models and forecast when considering ART as a prevention strategy.
Treatment of curable sexually transmitted infections (STIs), a relatively inexpensive, simple, and effective intervention, should be promoted as an essential component of HIV control programs in communities with a high incidence of STIs. The authors derived this from reviewing the observational studies and nine randomized controlled trials (RCTs) evaluating the impact of STI treatment interventions on HIV incidence. Although only one of nine RCTs has demonstrated an effect on HIV incidence, the authors conclude that issues in trial design and conduct--including HIV epidemic phase, STI prevalence, and intervention in comparison groups--affected several of the trials. The RCTs examined three different management approaches to a broad spectrum of curable and incurable STIs in varying populations, with different levels of risk behaviors and STI prevalence, in both concentrated and generalized HIV epidemic settings. Four of the trials focused on population-level effects of STI treatments, with only one focusing on populations with high STI prevalence. Three trials, focusing on herpes suppressive therapy, found that antivirals for herpes simplex virus suppression were insufficient to control the cofactor effect of herpes simplex virus type-2 on HIV transmission. The authors advocate for future research examining the biological mechanisms responsible for the STI-HIV interactions, testing new STI control strategies that target these interactions, and developing point-of-care STI diagnostics and evaluation of alternative partners service approaches (e.g., patient-delivered partner therapy).
This randomized, placebo-controlled clinical trial of acyclovir set out to determine whether or not the drug could reduce the transmission of HIV from partners co-infected with HIV and herpes simplex virus type-2 (HSV-2) to their serodiscordant partners. The study was conducted among over 3,400 serodiscordant couples in 14 sites in Southern and Eastern Africa. Although daily therapy with acyclovir reduced mean plasma concentrations of HIV and the occurrence of genital ulcers due to HSV-2, it did not cut the risk of HIV transmission, the study found. However, it proved the feasibility of conducting trials among HIV serodiscordant couples.
This study used confidential computerized interviews to ask people living with HIV about recent history of sexually transmitted infections (STIs) as well as their sexual behaviors and infectiousness beliefs. It found that one in seven respondents had been diagnosed with an STI over a six-month period, most commonly herpes simplex virus and syphilis. There was a strong association between belief that viral load was undetectable and diagnosis with an STI. The authors advocate integration of STI diagnosis and treatment into routine clinical HIV care. It is also crucial to correct false beliefs about infectiousness and provide education about STI symptom recognition and the importance of early detection and aggressive treatment, they write.
The Joint United Nations Programme on HIV/AIDS Mode of Transmission Model spreadsheet was used to assess the impact of various HIV prevention interventions based on data available from Malawi, taking into account the country's high prevalence of partner concurrency and serodiscordancy. Interventions in the model include increased condom use, more circumcisions, and converting all multiple concurrent partnerships into monogamous partnerships. The model showed that most new cases were among low-risk heterosexual groups (i.e., those who were part of serodiscordant couples or those who had casual sex and their partners). Condom use by discordant couples, a monogamy policy such as Uganda's Zero Grazing campaign, and abstinence were the most effective prevention measures; improved treatment of sexually transmitted infections had only a limited effect.
The prevalence and incidence of reproductive tract infections (RTIs) and HIV over a five-year period and the relationship between RTIs and HIV infection were examined in this study of more than 4,400 women attending family planning clinics in Zimbabwe and Uganda. Even though the women received regular counseling on risk reduction, screening, and treatment for RTIs, the incidence of HIV and RTIs did not diminish during the study period and almost all types of RTI were associated with increased risk of HIV infection. The authors still conclude that aggressive efforts to control RTIs may contribute significantly to HIV prevention and recommend continued efforts to find more effective treatments and interventions.
This small study offers an explanation for why treating herpes simplex virus type-2 (HSV-2) does not lead to a reduction in HIV acquisition even though infection with HSV-2 is associated with increased risk of HIV infection. Examining biopsies from eight subjects infected with HSV-2, the authors found that below healed herpes lesions, there is profound localized inflammation that persists even after prolonged antiviral therapy. Future interventions to break the association between HSV-2 and HIV should strive to reduce this inflammation or lead to the development of a HSV-2 vaccine, the authors conclude.
This randomized, double-blind, placebo-controlled trial enrolled HIV-negative, herpes simplex virus type 2 (HSV-2) seropositive women in Africa and men who have sex with men in Peru and the United States. Participants were given either acyclovir or placebo for 12 to 18 months. The primary endpoint was HIV acquisition, and the study showed that suppression of HSV-2 infection did not lead to a reduction in incidence of HIV. This is disappointing, the authors comment, given that infection with HSV-2 is associated with significantly higher risk of HIV acquisition. They recommend further studies re-examine this assumption derived from observational studies and whether higher doses of acyclovir or other antiviral drugs would yield better results.
The commentary is in response to two randomized controlled trials that tested the effect of STI treatment on HIV acquisition, both published in volume 371 of the Lancet in 2008. The first was conducted in Tanzania and the other was multicenter (HIV Prevention Trials Network 039). Both found no effect of herpes simplex virus type 2 suppression on HIV acquisition, a surprising result based on observational data. The authors provide plausible reasons on why this may have been found. Diagnosis and treatment of STIs is a public health responsibility; however, they conclude that HIV prevention strategies may need to be revised based on these new findings. Resources should be directed to strategies that are proven efficacious.
The commentary is in response to the view expressed by Gray and Wawer (in "Reassessing the Hypothesis on STI Control for HIV Prevention," Lancet 2008) that HIV prevention strategies should be adjusted based on the results from two randomized controlled trials showing no effect of STI control on HIV acquisition. The authors disagree with this view and support sexually transmitted infection control in HIV prevention founded on the results of modeling studies. Reducing funds to sexually transmitted infection diagnosis, treatment, and control could have adverse and unexpected effects on the HIV epidemic and should not be relaxed.
This study used a mathematical model to examine whether or not interventions to treat sexually transmitted infections (STIs) are cost-saving in populations with generalized HIV epidemics. The model was applied to the population characteristics of four cities in West Africa and East Africa, two with high HIV prevalence and two where prevalence was relatively low. It found that in settings where there is a generalized HIV epidemic, even though the proportion of HIV infections attributable to curable STIs is likely to fall, interventions targeting these diseases are still highly cost-effective and potentially cost-saving, assuming STIs have not been controlled by changes in risk behavior.
This study compared the impact of three scenarios--behavioral interventions with or without syndromic management of sexually transmitted infections and routine medical care--on incidence of HIV in rural Ugandan communities. Awareness of herpes simplex virus type-2 (HSV-2) symptoms improved in the behavioral intervention group and HSV-2 incidence decreased in the group that also received syndromic sexually transmitted infection management. The study took reported condom use with the last casual partner as a proxy for high-risk sexual encounters and found that the behavioral interventions were associated with increased condom use. However, there was no measurable reduction in the incidence of HIV in any of the groups.
This study looked at the impact of presumptive treatment of sexually transmitted infections on both HIV transmission and pregnancy outcome. The study randomized over 4,000 pregnant women to either one presumptive treatment for sexually transmitted infections during pregnancy or vitamin and mineral supplements, with confidential notification and treatment referral for those diagnosed with syphilis during the study. The intervention resulted in less cervical and vaginal infections and fewer cases of infant ophthalmia, as well as significantly lower rates of low birth weight and neonatal mortality. However, there was no change in maternal HIV acquisition or in mother-to-child HIV transmission.
This 2001 meta-analysis combined the best available evidence to date to examine the effect of sexually transmitted infections (STIs) on HIV susceptibility. It found that many studies had been done in this area, but that a quantitative understanding of the interaction between the two was still lacking. Although randomized controlled trials are the gold standard for proving causation, most studies on HIV and STIs were observational. The authors recommend that future studies should strive to quantify the extent to which treating STIs has an impact on HIV prevention.
This study sought to test the hypothesis that controlling sexually transmitted infections (STIs) at the population level would reduce the incidence of HIV, as had been found in the first clinical trial conducted in rural Tanzania. The study was conducted in clusters of villages that encompassed social, and therefore sexual, networks in a rural district in southwestern Uganda with high rates of both HIV and STIs. The intervention group participants were given mass treatment with antibiotics while the control group participants were given vitamins and treatment for parasitic worms. Although the prevalence and incidence of some STIs significantly reduced in the intervention group versus the control group, there was no difference in HIV incidence.
This was the first randomized controlled clinical trial to test the hypothesis that treating sexually transmitted infections (STIs) would reduce HIV infection. The STI intervention program was conducted in 12 large communities and included setting up a reference clinic and laboratory, diagnosis and treatment training for existing staff, supplying drugs, and visits to villages served by each health facility to encourage people to seek prompt treatment for STIs. The study found that in the intervention group, HIV incidence fell by more than two-fifths over two years, with the greatest impact among women aged 15 to 24 and men aged 25 to 34. Subsequent clinical trials have not been able to replicate these results.
This evaluation monitored the performance of Avahan, the India AIDS Initiative, using a supportive supervision tool to analyze outcomes from three perspectives: clinical, community, and management. The tool assessed the accessibility, acceptability, and contact coverage of sexually transmitted infection clinical services. It looked at barriers to access and monitored the quality of individual service components, including correct treatment, infection control, confidentiality, and counseling. Monitoring demonstrated that Avahan improved and sustained quality in terms of coverage, quality, technical support, community involvement, and networks of referrals. The monitoring tool provides timely and useful feedback but can be time-consuming and resource-intensive to implement.
This study used biological and behavioral surveys to assess the impact of HIV prevention programs targeted at female sex workers, such as peer outreach and behavior change communication and provision of sexual health clinic services including syndromic and presumptive management of sexually transmitted infections (STIs). By follow-up, almost all participants had been visited by a peer educator, at least three-quarters had visited a drop-in center or sexual health clinic, and two-thirds had received presumptive treatment for chlamydia and gonorrhea. Rates of condom use with clients improved but were static with regular partners. The prevalence of HIV reduced significantly across the board, but for curable STIs, only street-based female sex workers had a reduced prevalence at follow-up. Rates of curable STIs did not decrease for brothel- and home-based female sex workers.
Twenty-seven antiretroviral therapy programs in Africa, Asia, and South America were surveyed to determine the extent of preventive services they offered. The survey showed that prevention efforts in most programs focused on health education to change behavior, supply of male condoms, and prevention of mother-to-child transmission. Other interventions (e.g., protocols for partner notification and interventions for high-risk groups such as serodiscordant couples and adolescents) were less common. Few sites offered regular sexually transmitted infection screening. Survey respondents cited stigma, lack of financial resources, and high patient load as the main obstacles to implementing preventive services within antiretroviral therapy programs.
This paper argues that the "fractured paradigm" of HIV prevention separate from programs to tackle sexually transmitted infections (STIs) is counterproductive for both, given that weak control of STIs may undermine HIV prevention efforts. The paper reviews the components, benefits, and feasibility of STI control and offers an alternative, unified paradigm to tackle HIV together with other STIs. A useful table lays out the epidemiological parameters for integrating HIV prevention and STI control, detailing which target groups and diseases should get priority in which settings and when STI interventions are most effective in preventing HIV transmission.
In Haiti, voluntary HIV counseling and testing became a gateway to providing comprehensive sexual and reproductive health services including condom use promotion, family planning, maternal child health services, and services specifically for young people and survivors of sexual violence. Integration made sense because most HIV infections in Haiti are transmitted sexually, mother-to-child transmission is common, and people living with HIV face stigma and discrimination in accessing health services. Services evolved as needs were identified. Although such integration requires great efforts to overcome the stigma associated with HIV, providing access to a range of health services greatly improves uptake of HIV counseling and testing.
The randomized double-blinded and placebo-controlled trial enrolled Kenyan female sex workers to test whether the use of antibiotic prophylaxis to treat common sexually transmitted infections (STIs) would also reduce the rate of HIV acquisition. Four hundred and sixty-six seronegative sex workers were enrolled in the study. All women were provided with risk-reduction counseling, condoms, treatment of symptomatic STIs, and biannual screening and treatment for asymptomatic STIs. Oral azithromycin was given to half of the participants and the other half was given a placebo. There was no statistically significant difference between the treatment and placebo groups on HIV-1 incidence. Out of 35 seroconversion cases, 19 were in the treatment group and 16 were in the placebo group. There was a strong association between prior STI and incident HIV-1 infection, and a significant positive effect of azithromycin on the reduction of incidence and prevalence of bacterial STIs. A reduction in risky sexual behaviors in both groups was found. Condom use with all clients increased from less to 20 percent to more than 50 percent within one month. The number of clients per week decreased from more than 16 to less than 6 within six months. There was a correlation between HIV-1 infection and risky sexual behaviors within the year of seroconversion. The authors provide plausible reasons for the lack of effectiveness in reducing HIV-1 acquisition with azithromycin treatment in this population.
This study of Kenya's syndromic management program for sexually transmitted infections (STIs) used HIV sentinel surveillance data in patients with STIs to identify changes in the proportion of patients with three syndromes associated with increased HIV acquisition: genital ulcer disease, urethral discharge, and vaginal discharge. Incidence declined after the introduction of the program in 1995 and then increased again when free STI medication was no longer offered in 2001. As this was an ecological study, it was vulnerable to possible selection bias, and the authors recommend further studies such as randomized clinical trials to better understand the impact of complex interventions like STI syndromic management programs.
This review of programs implementing syndromic management of sexually transmitted infections (STIs) found that the processes for diagnosis and treatment of urethral discharge and genital ulcer disease in men were highly sensitive or had good cure rates, but those for women were less sensitive, particularly for those without symptoms. Algorithms for vaginal discharge do not effectively detect gonorrhea or chlamydia in women. Once the qualitative aspects of STI syndromic management are taken into account, the algorithms are likely to be even less sensitive than the literature suggests, and the authors urgently call for the development of affordable and effective rapid STI testing for use in resource-poor settings.
The Office of the Global AIDS Coordinator guidance is aimed at U.S. President's Emergency Plan for AIDS Relief (PEPFAR) country teams to provide them with the latest scientific data on prevention programs to increase the impact of their country portfolios. Prevention programs should be tailored to the epidemiological and social context of the country as well as optimizing on current programs implemented by other partners to help fill gaps. The guidance highlights the importance of knowing the country's epidemic, context, response, and costs, as well as ensuring that HIV prevention is part of the overall country continuum for the response. It also outlines current evidence and program activities that PEPFAR funds will support in relation to the diagnosis and treatment of sexually transmitted infections.
National- and regional-level decision makers can use this Programme Guidance Tool to set goals and priorities for interventions to address reproductive tract infections. The tool has 10 steps, 7 of which are for strategic situation analysis, followed by development of recommendations, implementation of new measures, and expansion of those found to be successful. It gives detailed guidance about what items should be covered at each stage. There is a section on how to conduct rapid assessment, including details on who should be interviewed and what interview tools can be used. There is also a suggested funding proposal outline for financing the first stage of the tool.
This sexually transmitted infection (STI) management training program can be used for in-service training of health care workers in health centers, district hospitals, STI clinics, or other first-level health facilities. Seven modules cover STI prevention and control, syndromic case management, history-taking and examination, diagnosis and treatment, patient counseling and education, partner management, and recording and development. There is a trainer's guide and a CD-ROM that can be used for self-learning or in conjunction with conventional training. The program is also available in French and Spanish.
These guidelines present sexually transmitted infections grouped by presenting symptom, with a section each for infections characterized by vaginal discharge, urethritis and cervicitis, and genital ulcers. Each section gives the range of recommended treatment regimens. The guidelines also cover partner management and special issues such as sexually transmitted infections during pregnancy; infections in babies, children, and adolescents; and, where applicable, treatment of drug-resistant disease strains. These guidelines are based on laboratory diagnosis rather than the syndromic management method that is used in resource-constrained settings.
These guidelines are part of a set of training materials that also includes a training manual, wall chart, and Arabic language promotional materials. The guidelines cover the syndromic management of sexually transmitted infections and have a diagnostic flow chart and treatment table for each common syndrome. They also highlight the importance of education and counseling as a component of both treatment and prevention of sexually transmitted infections. The training manual provides a sample workshop agenda and slides for each session. The wall chart, with a summary of symptom and treatment information, is ideal for use in clinics.
This guide is a reference manual for use in reproductive health care settings such as family planning and maternal and child health care clinics. It focuses on women, as they are the typical users of such clinics and are less likely to use sexually transmitted infection (STI) clinics. There are sections giving basic information on STIs and other reproductive tract infections (RTIs), improving prevention and treatment services, and the clinical management of RTIs. HIV is mentioned in the guide but is not covered extensively because it is not a disease of the reproductive tract.
Periodic Presumptive Treatment for Sexually Transmitted Infections: Experience from the Field and Recommendations for Research
World Health Organization. (2008).
This report describes experiences from the field in periodic and one-time presumptive treatment for sexually transmitted infections (STIs) among sex workers and their clients. The report followed on from a technical consultation on global experiences of presumptive STI treatment programs among high-risk populations. The consultation identified the conditions needed for effective STI control using presumptive treatment and produced recommendations for research. Both topics are covered in this report, as is the effect of presumptive treatment on specific STIs. The report presents case studies and offers brief guidance on operating such programs.
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The Global Strategy for the Prevention and Control of Sexually Transmitted Infections 2006-2015: Breaking the Chain of Transmission
World Health Organization. (2007).
This document makes the case for a global strategy to tackle sexually transmitted infections (STIs), describing the public health burden and the opportunities for an accelerated response such as the emergence of new and cost-effective technologies. The strategy aims to provide a framework for this response and is targeted at managers of national HIV prevention and STI control programs as well as other health sector stakeholders including health care providers, health ministers, and donors. It details both the technical strategy for STI prevention and control and an advocacy strategy for mobilizing resources and political and social leadership.
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Guidelines for the Management of Sexually Transmitted Infections
World Health Organization. (2003).
These guidelines lay out the standardized treatment recommendations for syndromes associated with sexually transmitted infections (STIs) using at-a-glance flowcharts and tables. There are also treatment recommendations for each specific STI. The guidelines detail the main considerations in choosing a treatment, such as cost, efficacy, treatment compliance, and availability. There is a chapter covering practical considerations in case management of STIs and another on treatment of STIs in children and adolescents.
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