Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples
Background:
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings:
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
Conclusions:
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
: Trial Registration: ClinicalTrials.com NCT00194519
Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples. PLoS Med 9(6): e32767. doi:10.1371/journal.pmed.1001251
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001251
Souhrn
Background:
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings:
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
Conclusions:
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
: Trial Registration: ClinicalTrials.com NCT00194519
Please see later in the article for the Editors' Summary
Zdroje
1. (UNAIDS) JUNPoHA 2010 Global report: UNAIDS report on the global AIDS epidemic 2010 New York UNAIDS
2. ChaissonREKerulyJCMooreRD 2000 Association of initial CD4 cell count and viral load with response to highly active antiretroviral therapy. JAMA 284 3128 3129
3. GrahamSMHolteSEPeshuNMRichardsonBAPanteleeffDD 2007 Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS 21 501 507
4. DonnellDBaetenJMKiarieJThomasKKStevensW 2010 Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 375 2092 2098
5. CohenMSChenYQMcCauleyMGambleTHosseinipourMC 2011 Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365 493 505
6. FredricksDNFiedlerTLMarrazzoJM 2005 Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 353 1899 1911
7. MitchellCMoreiraCFredricksDPaulKCaliendoAM 2009 Detection of fastidious vaginal bacteria in women with HIV infection and bacterial vaginosis. Infect Dis Obstet Gynecol 2009 236919
8. BukusiEACohenCRMeierASWaiyakiPGNgutiR 2006 Bacterial vaginosis: risk factors among Kenyan women and their male partners. Sex Transm Dis 33 361 367
9. MartinHLRichardsonBANyangePMLavreysLHillierSL 1999 Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180 1863 1868
10. SewankamboNGrayRHWawerMJPaxtonLMcNaimD 1997 HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet 350 546 550
11. AtashiliJPooleCNdumbePMAdimoraAASmithJS 2008 Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS 22 1493 1501
12. ColemanJSHittiJBukusiEAMwachariCMuliroA 2007 Infectious correlates of HIV-1 shedding in the female upper and lower genital tracts. AIDS 21 755 759
13. ShaBEZariffardMRWangQJChenHYBremerJ 2005 Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis 191 25 32
14. WangCCMcClellandRSReillyMOverbaughJEmerySR 2001 The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. J Infect Dis 183 1017 1022
15. HashemiFBGhassemiMFaroSAroutchevaASpearGT 2000 Induction of human immunodeficiency virus type 1 expression by anaerobes associated with bacterial vaginosis. J Infect Dis 181 1574 1580
16. SimoesJAHashemiFBAroutchevaAAHeimlerISpearGT 2001 Human immunodeficiency virus type 1 stimulatory activity by Gardnerella vaginalis: relationship to biotypes and other pathogenic characteristics. J Infect Dis 184 22 27
17. ClemetsonDBMossGBWillerfordDMHenselMEmonyiW 1993 Detection of HIV DNA in cervical and vaginal secretions. Prevalence and correlates among women in Nairobi, Kenya. JAMA 269 2860 2864
18. RebbapragadaAHoweKWachihiCPettengellCSunderjiS 2008 Bacterial vaginosis in HIV-infected women induces reversible alterations in the cervical immune environment. J Acquir Immune Defic Syndr 49 520 522
19. CelumCWaldALingappaJRMagaretASWangRS 2010 Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med 362 427 439
20. NugentRPKrohnMAHillierSL 1991 Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29 297 301
21. ForsumUJakobssonTLarssonPGSchmidtHBeverlyA 2002 An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis. APMIS 110 811 818
22. CampbellMSMullinsJIHughesJPCelumCWongKG 2011 Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial. PLoS One 6 e16986 doi:10.1371/journal.pone.0016986
23. LingappaJRBaetenJMWaldAHughesJPThomasKK 2009 Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet 375 824 833
24. SahaiH 1996 Statistics in epidemiology: methods, techniques, and applications. SahaiHKhurshidA Boca Raton (Florida) CRC Press
25. BaetenJMKahleELingappaJRCoombsRWDelany-MoretlweS 2011 Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med 3 77ra29
26. TantonCWeissHALe GoffJChangaluchaJRusizokaM 2011 Correlates of HIV-1 genital shedding in Tanzanian Women. PLoS One 6 e17480 doi:10.1371/journal.pone.0017480
27. MoreiraCVenkateshKKDeLongALiuTKurpewskiJ 2009 Effect of treatment of asymptomatic bacterial vaginosis on HIV-1 shedding in the genital tract among women on antiretroviral therapy: a pilot study. Clin Infect Dis 49 991 992
28. CohenCRPlummerFAMugoNMacleanIShenC 1999 Increased interleukin-10 in the the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission? AIDS 13 327 332
29. BukusiEAThomasKNgutiRCohenCRWeissN 2011 Topical penile microbicide use by men to prevent recurrent bacterial vaginosis in sex partners: a randomized clinical trial. Sex Transm Dis 38 483 489
30. GrayRHKigoziGSerwaddaDMakumbiFNalugodaF 2009 The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. Am J Obstet Gynecol 200 42 e41 e47
31. PriceLBLiuCMJohnsonKEAzizMLauMK 2010 The effects of circumcision on the penis microbiome. PLoS One 5 e8422 doi:10.1371/journal.pone.0008422
32. DonovalBALandayALMosesSAgotKNdinya-AcholaJO 2006 HIV-1 target cells in foreskins of African men with varying histories of sexually transmitted infections. Am J Clin Pathol 125 386 391
33. de JongMAGeijtenbeekTB 2009 Human immunodeficiency virus-1 acquisition in genital mucosa: Langerhans cells as key-players. J Intern Med 265 18 28
34. KlebanoffMASchwebkeJRZhangJNanselTRYuKF 2004 Vulvovaginal symptoms in women with bacterial vaginosis. Obstet Gynecol 104 267 272
35. AmselRTottenPASpiegelCAChenKCEschenbachD 1983 Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 74 14 22
36. BaetenJMStrickLBLucchettiAWhittingtonWLSanchezJ 2008 Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. J Infect Dis 198 1804 1808
37. EschenbachDA 1993 History and review of bacterial vaginosis. Am J Obstet Gynecol 169 441 445
38. GreenblattRMBacchettiPBarkanSAugenbraunMSilverS 1999 Lower genital tract infections among HIV-infected and high-risk uninfected women: findings of the Women's Interagency HIV Study (WIHS). Sex Transm Dis 26 143 151
39. BradshawCSMortonANHockingJGarlandSMMorrisMB 2006 High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis 193 1478 1486
40. TabriziSNFairleyCKBradshawCSGarlandSM 2006 Prevalence of Gardnerella vaginalis and Atopobium vaginae in virginal women. Sex Transm Dis 33 663 665
41. VerstraelenHVerhelstRVaneechoutteTemmermanMM The epidemiology of bacterial vaginosis in relation to sexual behaviour. BMC Infect Dis 10 81
42. McClellandRSRichardsonBAHassanWMChohanVLavreysL 2008 Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: results of a randomized trial. J Infect Dis 197 1361 1368
43. AnukamKCOsazuwaEOsemeneGIEhigiagbeFBruceAW 2006 Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect 8 2772 2776
44. BoltonMvan der StratenACohenCR 2008 Probiotics: potential to prevent HIV and sexually transmitted infections in women. Sex Transm Dis 35 214 225
45. HemmerlingAHarrisonWSchroederAParkJKornA 2010 Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis 37 745 750
46. SwidsinskiAMendlingWLoening-BauckeVLadhoffASwidsinskiS 2005 Adherent biofilms in bacterial vaginosis. Obstet Gynecol 106 1013 1023
47. SwidsinskiAMendlingWLoening-BauckeVSwidsinskiSDorffelY 2008 An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 198 97 e91 96
48. ThomaMEGrayRHKiwanukaNAlumaSWangMC 2011 The Short-term Variability of Bacterial Vaginosis Diagnosed by Nugent Gram Stain Criteria Among Sexually Active Women in Rakai, Uganda. Sex Transm Dis 38 111 116
49. WawerMJSewankamboNKSerwaddaDQuinnTCPaxtonLA 1999 Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 353 525 535
50. HemmerlingACohenCR 2011 Probiotics: the potential for a live microbicide to prevent HIV. J Acquir Immune Defic Syndr 56 e98 101
51. MacPheeRAHummelenRBisanzJEMillerWLReidG 2010 Probiotic strategies for the treatment and prevention of bacterial vaginosis. Expert Opin Pharmacother 11 2985 2995
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