the role of sexually transmitted diseases in hiv transmission

REVIEWSbehaviour. A higher prevalence of HSV infection, trichomoniasisin women and a lower prevalence of malecircumcision were the main factors that correlated significantlywith areas of high HIV prevalence, whereasfactors such as condom use, sexual partnerships andbehaviour, and N. gonorroheae, C. trachomatis andT. pallidum infections were less correlated with HIVprevalence 8 . HSV infection was a strong HIV-risk factor,and was documented in up to 86% of women in thehigh-prevalence areas of Kisumu and Ndola.Although the overall rates of HSV infection inCotonou and Yaounde were also significant at 29.5%and 50.9%, respectively, the difference in HSV prevalencebetween the high- and low-HIV-infected areaswas most pronounced among women under 25 yearsof age. This is important as women under 25 have avery high prevalence of HIV infection in Kisumu andNdola 105 , and differences in sexual behaviour couldnot account for this.The Mwanza (Tanzania) STD intervention trial. In thistrial, investigators undertook a prevention study thatwas focused on health education, risk reduction andSTD recognition and detection in a region ofTanzania 106 .In communities that were receiving STDintervention, an STD reference clinic, enhancedtraining and supervision of medical staff, a regularsupply of drugs and community health educationwere all available. Six pair-matched comparison communitiesreceived standard care. The incidence ofHIV was reduced by 40% in the communities receivingenhanced STD care 106 .The Rakai (Uganda) mass therapy trial. In this study,three rounds of mass antibiotic therapy were givenevery 10 months over a 20 month period to experimentalcommunities. HIV-prevention activities andimproved general healthcare were available in bothexperimental and control communities . Mass therapyreduced the prevalence of syphilis and trichomonas,reduced the incidence of trichomonas and also causedtransitory changes in BV. However, the incidence ofHIV infection was not affected 101 .Further studies. In a more recent study in Uganda, ruralcommunities were randomized to receive behaviouralinterventions, behavioural and enhanced STD treatment,or routine care. Across all groups, there was an overallincrease in condom use and a decrease in high-risk sexualbehaviour; in the groups receiving behavioural interventionand enhanced STD treatment, condom use washigher than the group receiving routine care . The incidenceof HSV decreased in the behavioural group andgonorrhoea and syphilis decreased in the STD treatmentgroup. However, no difference was seen in the incidenceof HIV infection between either intervention group 107 .Another study randomized HIV-negative Kenyanfemale sex workers to receive monthly azithromycin orplacebo. The incidence of gonorrhoea, chlamydia andtrichomonas decreased in the treatment group, butthere was no effect on the incidence of HIV infection 108 .Interpreting community-based interventions. Aremarkable number of articles comparing and interpretingthe results of these large intervention trials havebeen published 34–36,109 ,focusing particularly on the differencesin the effects that were seen in the Mwanza andRakai trials. The arguments that have been used toaccount for the positive effect seen in Mwanza comparedwith the lack of effect seen in Rakai include:mebendazole — the placebo that was used in the Rakaitrial — treats worm infections, which affected the viralburden in the index case; improved STD treatment wasa more powerful intervention than intermittent masstherapy; symptomatic STDs in HIV-infected individualsare of the greatest importance, and such subjectswould be expected to be overrepresented in theMwanza trial; STDs might be more important in earlyepidemics (for example, in Mwanza) than in late epidemics;and the STDs that were studied have differentimportances. Also, HSV-2 infection, which would nothave been treated by the antibiotic therapy that wasused in the Rakai trial, and the genital ulcers documentedin Rakai could have been influential factors inthe HIV epidemic. Additionally, it has been hypothesizedthat in the Rakai trial, the end of the Ugandan civilwar resulted in less ‘risky’ behaviours at the time the trialwas conducted, and therefore might have reduced theoverall incidence of STDs and HIV — thereby maskingany effects of STD treatment 109 ; although the morerecent study by Kamali et al. also showed no reductionin the incidence of HIV infection. Overall, improvingthe control of STDs has had disappointing effects onthe incidence of HIV infection. Possibly, reducingSTDs might have a greater effect in the early stages ofan epidemic, where HIV is still found mainly in highriskgroups such as in India or eastern Europe. Finally,trials that attempt to treat HSV aggressively might showimproved outcomes.Summary and conclusionsPreventing the spread of HIV is one of the greatestchallenges of the twenty-first century. An overwhelmingbody of evidence indicates that STDs that causemucosal inflammation and ulcers contribute to thespread of HIV, by increasing infectiousness, susceptibilityor both. However, the benefits of detection andtreatment of STDs in combating the spread of HIVhave been more difficult to prove. It has been difficultto identify and treat the STDs of greatest potentialimportance, and to treat STDs in the populations thatare likely to experience the greatest benefit from suchan intervention. India, eastern European countries,Russia and China are now experiencing rapid increasesin the prevalence of HIV and STDs 47,110 .In China, forexample, the economic reforms of the 1980s have ledto an STD epidemic 111 and a high risk of the heterosexualspread of HIV, especially through commercial sexworkers 112 .A focus on STDs is therefore an importantpart of HIV prevention, especially in countries withemerging HIV epidemics. Further research must definethe STDs that deserve the greatest attention, and themost effective STD intervention strategy.40 | JANUARY 2004 | VOLUME 2 www.nature.com/reviews/micro