HIV Prevention Knowledge Base
Biomedical Interventions: Diagnosis and Treatment of Sexually Transmitted Infections
Prevalence of Sexually Transmitted Co-infection in People Living with HIV/AIDS: Systematic Review with Implications for Using HIV Treatments for Prevention
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 Sexually Transmitted Infections for HIV Prevention: End of the Road or New Beginning?
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).
Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2
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.
Sexually Transmitted Infections and Infectiousness Beliefs Among People Living With HIV/AIDS: Implications for HIV Treatment as Prevention
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.
Selecting HIV Infection Prevention Interventions in the Mature HIV Epidemic in Malawi Using the Mode of Transmission Model
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.
Disentangling Contributions of Reproductive Tract Infections to HIV Acquisition in African Women
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.
Persistence of HIV-1 Receptor–Positive Cells After HSV-2 Reactivation is a Potential Mechanism for Increased HIV-1 Acquisition
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.
Effect of Acyclovir on HIV-1 Acquisition in Herpes Simplex Virus 2 Seropositive Women and Men Who Have Sex With Men: A Randomized, Double-Blind, Placebo-Controlled Trial
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.
Reassessing the Hypothesis on STI Control for HIV Prevention
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.
Control of Sexually Transmitted Infections for HIV Prevention
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.
Treating Curable Sexually Transmitted Infections to Prevent HIV in Africa. Still an Effective Control Strategy?
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.
Syndromic Management of Sexually Transmitted Infections and Behavior Change Interventions on Transmission of HIV-1 in Rural Uganda: A Community Randomised Trial
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.
Randomized Trial of Presumptive Sexually Transmitted Disease Therapy During Pregnancy in Rakai, Uganda
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.
A Systematic Review of the Epidemiologic Interactions Between Classic Sexually Transmitted Diseases and HIV: How Much Really is Known?
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.
Control of Sexually Transmitted Diseases for AIDS Prevention in Uganda: A Randomised Community Trial
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.
Impact of Improved Treatment of Sexually Transmitted Diseases on HIV Infection in Rural Tanzania: Randomised Controlled Trial
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.