Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Aug 15;2012(8):CD007933.
doi: 10.1002/14651858.CD007933.pub2.

Genital ulcer disease treatment for reducing sexual acquisition of HIV

Affiliations
Meta-Analysis

Genital ulcer disease treatment for reducing sexual acquisition of HIV

Florence M Mutua et al. Cochrane Database Syst Rev. .

Abstract

Background: Genital ulcer disease by virtue of disruption of the mucosal surfaces may enhance HIV acquisition. Genital ulcer disease treatment with resolution of the ulcers may therefore contribute in reducing the sexual acquisition of HIV.

Objectives: To determine the effects of treatment of genital ulcer disease on sexual acquisition of HIV.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, LILACS, NLM Gateway, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of relevant publications for eligible studies published between 1980 and August 2011.

Selection criteria: Randomized controlled trials of any treatment intervention aimed at curing genital ulcer disease compared with an alternative treatment, placebo, or no treatment. We included only trials whose unit of randomization was the individual with confirmed genital ulcer.

Data collection and analysis: We independently selected studies and extracted data in duplicate; resolving discrepancies by discussion, consensus, and arbitration by third review author. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI).

Main results: There were three randomized controlled trials that met our inclusion criteria recruited HIV-negative participants with chancroid (two trials with 143 participants) and primary syphilis (one trial with 30 participants). The syphilis study, carried out in the US between 1995 and 1997, randomized participants to receive a single 2.0 g oral dose of azithromycin (11 participants); two 2.0 g oral doses of azithromycin administered six to eight days apart (eight participants); or benzathine penicillin G administered as either 2.4 million units intramuscular injection once or twice seven days apart (11 participants). No participant in the trial seroconverted during 12 months of follow-up. The chancroid trials, conducted in Kenya by 1990, found no significant differences in HIV seroconversion rates during four to 12 weeks of follow-up between 400 and 200 mg single oral doses of fleroxacin (one trial, 45 participants; RR 3.00; 95% CI 0.29 to 30.69), or between 400 mg fleroxacin and 800 mg sulfamethoxazole plus 160 mg trimethoprim (one trial, 98 participants; RR 0.33; 95% CI 0.04 to 3.09). Adverse events reported were mild to moderate in severity, and included Jarisch-Herxheimer reactions and gastrointestinal symptoms. The differences between the treatment arms in the incidence of adverse events were not significant. The quality of this evidence on the effectiveness of genital ulcer disease treatment in reducing sexual acquisition of HIV, according to GRADE methodology, is of very low quality.

Authors' conclusions: At present, there is insufficient evidence to determine whether curative treatment of genital ulcer disease would reduce the risk of HIV acquisition. The very low quality of the evidence implies that the true effect of genital ulcer disease treatment on sexual acquisition of HIV may be substantially different from the effect estimated from currently available data. However, genital ulcer diseases are public health problems in their own right and patients with these conditions should be treated appropriately; whether the treatment reduces the risk of HIV infection or not.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
PRISMA flow diagram showing the search and selection of studies.
2
2
3
3
1.1
1.1. Analysis
Comparison 1 Treatment of syphilis, Outcome 1 HIV seroconversion.
1.2
1.2. Analysis
Comparison 1 Treatment of syphilis, Outcome 2 HIV seroconversion.
2.1
2.1. Analysis
Comparison 2 Treatment of chancroid, Outcome 1 HIV seroconversion.
2.2
2.2. Analysis
Comparison 2 Treatment of chancroid, Outcome 2 HIV seroconversion.

Update of

  • doi: 10.1002/14651858.CD007933

Similar articles

Cited by

References

References to studies included in this review

Hook 2002 {published data only}
    1. Hook EW, Martin DH, Stephens J, Smith BS, Smith K. A randomised, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sexually Transmitted Diseases 2002;29:486‐90. - PubMed
MacDonald 1989 {published data only}
    1. MacDonald KS, Cameron DW, D'Costa L, Ndinya‐Achola JO, Plummer FA, Ronald AR. Evaluation of fleroxacin (RO 23‐6240) as single‐oral‐dose therapy of culture‐proven chancroid in Nairobi, Kenya. Antimicrobial Agents and Chemotherapy 1989;33:612‐4. - PMC - PubMed
Plourde 1992 {published data only}
    1. Plourde PJ, D'Costa LJ, Agoki E, Ombette J, Ndinya‐Achola JO, Slaney LA, et al. A randomised, double‐blind study of the efficacy of fleroxacin versus trimethoprim‐sulfamethoxazole in men with culture‐proven chancroid. Journal of Infectious Diseases 1992; Vol. 165:949‐52. [CN‐00083475] - PubMed

References to studies excluded from this review

Gregson 2007 {published data only}
    1. Gregson S, Adamson S, Papaya S, Mundondo J, Nyamukapa CA, Mason PR, et al. Impact and process evaluation of integrated community and clinic‐based HIV‐1 control: a cluster‐randomised trial in eastern Zimbabwe. PLoS Medicine 2007;4(3):e102. - PMC - PubMed
Grosskurth 1995 {published data only}
    1. Grosskurth H, Mosha F, Todd J, Mwijarubi E, Klokke A, Senkoro K, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995;346:530‐6. - PubMed
Hook 2010 {published data only}
    1. Hook EW, Behets F, Damme K, Ravelomanana N, Leone P, Sena AC, et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. Journal of Infectious Diseases 2010;201:1729‐35. - PubMed
Kamali 2003 {published data only}
    1. Kamali A, Quigley M, Nakiyingi J, Kinsman J, Kengeya‐Kayondo J, Gopal R, et al. Syndromic management of sexually‐transmitted infections and behaviour change interventions on transmission of HIV‐1 in rural Uganda: a community randomised trial. Lancet 2003;361:645‐52. - PubMed
Malonza 1999 {published data only}
    1. Malonza IM, Tyndall MW, Ndinya‐Achola JO, Maclean I, Omar S, MacDonald KS, et al. A randomised, double‐blind, placebo‐controlled trial of single‐dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya. Journal of Infectious Diseases 1999;180:1886‐93. - PubMed
Moodley 2003 {published data only}
    1. Moodley P, Sturm PDJ, Vanmali T, Wilkinson D, Connolly C, Sturm AW. Association between HIV‐1 infection, the etiology of genital ulcer disease, and response to syndromic management. Sexually Transmitted Diseases 2003;30:241‐5. - PubMed
Riedner 2005 {published data only}
    1. Riedner G, Rusizoka M, Todd J, Maboko L, Hoelscher M, Mmbando D, et al. Single‐dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. New England Journal of Medicine 2005;353:1236‐44. - PubMed
Rolfs 1997 {published data only}
    1. Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M, et al. A randomised trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. New England Journal of Medicine 1997;337:307‐14. - PubMed
Tyndall 1994 {published data only}
    1. Tyndall MW, Agoki E, Plummer FA, Malisa W, Ndinya‐Achola JO, Ronald AR. Single dose azithromycin for the treatment of chancroid: a randomised comparison with erythromycin. Sexually Transmitted Diseases 1994;21:231‐4. - PubMed
Wawer 1998 {published data only}
    1. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Paxton L, Berkley S, et al. A randomised, community‐based trial of intense sexually transmitted diseases control for AIDS prevention, Rakai, Uganda. AIDS 1998;12:1211‐25. - PubMed
    1. Wawer MJ, Sewankambo NK, Serwadda D, Quinn TC, Paxton LA, Kiwanuka N, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 1999;353:525‐35. - PubMed

Additional references

Baeten 2008
    1. Baeten JM, Strick LB, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, et al. Herpes simplex virus (HSV)‐suppressive therapy decreases plasma and genital HIV‐1 levels in HSV‐2/HIV‐1 co‐infected women: a randomised, placebo controlled, cross‐over trial. Journal of Infectious Diseases 2008;198:1804‐8. - PMC - PubMed
Balshem 2011
    1. Balshem B, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Broze J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64:401‐6. - PubMed
Barnabas 2011
    1. Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, et al. Impact of herpes simplex virus type 2 on HIV‐1 acquisition and progression in an HIV vaccine trial (the Step Study). Journal of Acquired Immune Deficiency Syndromes 2011;57:238‐44. - PMC - PubMed
Boily 2009
    1. Boily M‐C, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al. Heterosexual risk of HIV‐1 infection per sexual act: systematic review and meta‐analysis of observational studies. Lancet Infectious Diseases 2009;9:118‐29. - PMC - PubMed
Brown 2007
    1. Brown JM, Wald A, Hubbard A, Rungruengthanakit K, Chipato T, Rugpao S, et al. Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe. AIDS 2007;21:1515‐23. - PubMed
Buchacz 2004
    1. Buchacz K, Patel P, Taylor M, Kerndt PR, Byers RH, Holmberg SD, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV‐infected patients with new syphilis infections. AIDS 2004;18:2075‐79. - PMC - PubMed
Cameron 1989
    1. Cameron DW, Simonsen JN, D'Costa LJ, Ronald AR, Maitha GM, Gakinya MN, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989;2:403‐07. - PubMed
CDC 2010
    1. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. Morbidity and Mortality Weekly Report 2010;59:No. RR‐12. - PubMed
Celum 2004
    1. Celum C, Levine R, Weaver M, Wald A. Genital herpes and human immunodeficiency virus: double trouble. Bulletin of the World Health Organization 2004;82:447‐53. - PMC - PubMed
Celum 2008
    1. Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany‐Moretlwe S, et al. Effect of aciclovir on HIV‐1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double‐blind, placebo‐controlled trial. Lancet 2008;371:2109‐19. - PMC - PubMed
Cohen 1997
    1. Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC, et al. Reduction of concentration of HIV‐1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV‐1. Lancet 1997;349:1868‐73. - PubMed
Cohen 2006
    1. Cohen MS. When people with HIV get syphilis: triple jeopardy. Sexually Transmitted Diseases 2006;33:149‐50. - PubMed
Corey 2004
    1. Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus‐2 on HIV‐1 acquisition and transmission: a review of two overlapping epidemics. Journal of Acquired Immune Deficiency Syndrome 2004;35:435‐45. - PubMed
Delany 2009
    1. Delany S, Mlaba N, Clayton T, Akpomiemie G, Capovilla A, LeGoff, et al. Impact of aciclovir on genital and plasma HIV‐1 RNA in HSV‐2/HIV‐1 co‐infected women: a randomised placebo‐controlled trial in South Africa. AIDS 2009;23:461–69. - PMC - PubMed
Dunne 2008
    1. Dunne EF, Whitehead S, Sternberg M, Thepamnuay S, Leelawiwat W, McNicholl JM, et al. Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV‐ and HSV‐2‐infected women, Chiang Rai, Thailand. Journal of Acquired Immune Deficiency Syndrome 2008;49:77‐83. - PubMed
Fleming 1999
    1. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sexually Transmitted Infections 1999;75:3‐17. - PMC - PubMed
Freeman 2006
    1. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ, et al. Herpes simplex virus infection increases HIV acquisition in men and women: systematic review and meta‐analysis of longitudinal studies. AIDS 2006;20:73‐83. - PubMed
Gray 2001
    1. Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire‐Mangen F, et al. Probability of HIV‐1 transmission per coital act in monogamous, heterosexual, HIV‐1 discordant couples in Rakai, Uganda. Lancet 2001;357:1149‐53. - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924‐26. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Johnson 2008
    1. Johnson LF, Lewis DA. The effect of genital tract infections on HIV‐1 shedding in the genital tract: a systematic review and meta‐analysis. Sexually Transmitted Disease 2008;35:946‐59. - PubMed
Kalichman 2011
    1. Kalichman SC, Pellowski J, Turner C. Prevalence of sexually transmitted co‐infections in people living with HIV/AIDS: systematic review with implications for using HIV treatments for prevention. Sexually Transmitted Infection 2011;87:183‐90. - PMC - PubMed
Laga 1993
    1. Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N, et al. Non‐ulcerative sexually transmitted diseases as risk factors for HIV‐1 transmission in women: results from a cohort study. AIDS 1993;7:95‐102. - PubMed
LeGoff 2007
    1. LeGoff J, Weiss HA, Gresenguet G, Nzambi K, Frost E, Hayes RJ, et al. Cervciovaginal HIV‐1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes. AIDS 2007;21:1569‐78. - PubMed
Mayaud 2001
    1. Mayaud P, McCormick D. Interventions against sexually transmitted infections (STIs) to prevent HIV infections. British Medical Bulletin 2001;58:129‐53. - PubMed
Mayaud 2009
    1. Mayaud P, LeGoff J, Weiss HA, Grésenguet G, Nzambi K, Bouhlal H, et al. Impact of acyclovir on genital and plasma HIV‐1RNA, genital hHerpes simplex virus type 2 DNA, and ulcer healing among HIV‐1–infected African women with herpes ulcers: a randomized placebo‐controlled trial. Journal of Infectious Diseases 2009;200:216‐26. - PubMed
Mayer 2011
    1. Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. American Journal of Reproductive Immunology 2011;65:308‐16. - PMC - PubMed
McCoy 2009
    1. McCoy SI, Eron JJ, Kuruc JD, Strauss RP, MacDonald PDM, Fiscus SA, et al. Sexually transmitted infections among patients with acute HIV in North Carolina. Sexually Transmitted Diseases 2009;36:372‐4. - PMC - PubMed
Muller 2010
    1. Muller EE, Chirwa TF, Lewis DA. Human papillomavirus (HPV) infection in heterosexual South African men attending sexual health services: associations between HPV and HIV serostatus. Sexually Transmitted Infections 2010;86:175‐80. - PubMed
Ng 2011
    1. Ng BE, Butler LM, Horvath T, Rutherford GW. Population‐based biomedical sexually transmitted infection control interventions for reducing HIV infection. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD001220.pub3] - DOI - PubMed
Paz‐Bailey 2010
    1. Paz‐Bailey G, Sternberg M, Puren AJ, Steele L, Lewis DA. Determinants of HIV type 1 shedding from genital ulcers among men in South Africa. Clinical Infectious Diseases 2010;50:1060‐7. - PubMed
Phiri 2010
    1. Phiri S, Hoffman IF, Weiss HA, Martinson F, Nyirenda N, Kamwendo D, et al. Impact of aciclovir on ulcer healing, lesional, genital and plasma HIV‐1 RNA among patients with genital ulcer disease in Malawi. Sexually Transmitted Infections 2010;86:345‐52. - PubMed
Plourde 1994
    1. Plourde PJ, Pepin J, Agoki E, Ronald AR, Ombette J, Tyndall M, et al. Human immunodeficiency virus type 1 seroconversion in women with genital ulcers. Journal of Infectious Diseases 1994;170:313‐7. - PubMed
Plummer 1991
    1. Plummer FA, Simonsen JN, Cameron DW, Ndinya‐Achola JO, Kreiss JK, Gakinya MN, et al. Cofactors in male‐female sexual transmission of human immunodeficiency virus type 1. Journal of Infectious Diseases 1991;163:233‐9. - PubMed
Quinn 1996
    1. Quinn TC. Association of sexually transmitted diseases and infection with the human immunodeficiency virus: biological cofactors and markers of behavioural interventions. International Journal of STD & AIDS 1996;7 Suppl 2:17‐24. - PubMed
Royce 1997
    1. Royce R, Seńa A, Cates W, Cohen MS. Sexual transmission of HIV. New England Journal of Medicine 1997;336:1072‐8. - PubMed
Schaker 1998
    1. Schaker T, Ryncarz AJ, Goddard J, Diem K, Shaughnessy M, Corey L. Frequent recovery of HIV‐1 from genital herpes simplex virus lesions in HIV‐1 infected men. JAMA 1998;280:61‐6. - PubMed
Smith 2010
    1. Smith JS, Moses S, Hudgens MG, Parker CB, Agot K, Maclean I, et al. Increased risk of HIV acquisition among Kenyan men with human papillomavirus infection. Journal of Infectious Diseases 2010;201:1677‐85. - PMC - PubMed
Tanton 2010
    1. Tanton C, Weiss HA, Goff J, Changalucha J, Rusizoka M, Baisley K, et al. Correlates of HIV‐1 genital shedding in Tanzanian women. PLoS ONE 2010;6(3):e17480. - PMC - PubMed
van de Wijgert 2009
    1. Wijgert JHHM, Morrison CS, Brown J, Kwok C, Pol B, Chipato T, et al. Disentangling contributions of reproductive tract infections to HIV acquisition in African women. Sexually Transmitted Diseases 2009;36:357‐64. - PubMed
Venkatesh 2011
    1. Venkatesh KK, Straten A, Cheng H, Montgomery ET, Lurie MN, Chipato T, et al. The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study. International Journal of STD & AIDS 2011;22:218‐24. - PubMed
Wang 2001
    1. Wang CC, McClelland RS, Reilly M, Overbaugh J, Emery SR, Mandaliya K, et al. The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. Journal of Infectious Diseases 2001;183:1017‐22. - PubMed
Wasserheit 1992
    1. Wasserheit JN. Epidemiological synergy: Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sexually Transmitted Diseases 1992;19:61‐77. - PubMed
Watson‐Jones 2008
    1. Watson‐Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. New England Journal of Medicine 2008;358:1560‐71. - PMC - PubMed
WHO 2001
    1. World Health Organization. Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. World Health Organization, 2001.
WHO 2007
    1. World Health Organization. Global strategy for the prevention and control of sexually transmitted infections: 2006 ‐ 2015: breaking the chain of transmission. World Health Organization, 2007.
WHO 2011
    1. World Health Organization. Global HIV/AIDS response: epidemic update and health sector progress towards universal access: progress report 2011. World Health Organization, 2011.
Zuckerman 2009
    1. Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Magaret A, et al. HSV suppression reduces seminal HIV‐1 levels in HIV‐1/HSV‐2 co‐infected men who have sex with men. AIDS 2009;23:479–83. - PMC - PubMed

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources