Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study

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Background:
Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1–infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1–uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.

Methods and Findings:
We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.

Conclusions:
Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention.

: Please see later in the article for the Editors' Summary

Vyšlo v časopise: Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study. PLoS Med 8(11): e32767. doi:10.1371/journal.pmed.1001123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001123

Souhrn

Zdroje

1. UNAIDS 2010 UNAIDS Report on the Global AIDS Epidemic. Available: http://www.unaids.org/GlobalReport/Global_report.htm. Geneva: UNAIDS

2. JahnAFloydSCrampinACMwaunguluFMvulaH 2008 Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi. Lancet 371 1603 1611

3. MayMBoulleAPhiriSMessouEMyerL 2010 Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes. Lancet 376 449 457

4. HechtRStoverJBollingerLMuhibFCaseK 2010 Financing of HIV/AIDS programme scale-up in low-income and middle-income countries, 2009-31. Lancet 376 1254 1260

5. The aids2031 Consortium 2011 AIDS: taking a long term view Upper Saddle River (New Jersey) FT Press

6. SchwartlanderBStoverJHallettTAtunRAvilaC 2011 Towards an improved investment approach for an effective response to HIV/AIDS. Lancet 377 2031 2041

7. KimSCBeckerSDieffenbachCHanewallBSHankinsC 2010 Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities. J Int AIDS Soc 13 24

8. UnderhillKOperarioDMimiagaMJSkeerMRMayerKH 2010 Implementation science of pre-exposure prophylaxis: preparing for public use. Curr HIV/AIDS Rep 7 210 219

9. CohenMSChenYQMcCauleyMGambleTHosseinipourMC 2011 Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365 493 505

10. Abdool KarimQAbdool KarimSSFrohlichJAGroblerACBaxterC 2010 Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329 1168 1174

11. University of Washington 2011 Pivotal study finds that HIV medications are highly effective as prophylaxis against HIV infection in men and women in Africa. Available: http://depts.washington.edu/astda/resources/PrEP_PressRelease-UW_13Jul2011.pdf. Accessed 17 October 2011

12. Centers for Disease Control and Prevention 2011 CDC trial and another major study find PrEP can reduce risk of HIV infection among heterosexuals. Available: http://www.cdc.gov/nchhstp/newsroom/PrEPHeterosexuals.html. Accessed 17 October 2011

13. De CockKMCrowleySPLoYRGranichRMWilliamsBG 2009 Preventing HIV transmission with antiretrovirals. Bull World Health Organ 87 488 488A

14. GostinLOKimSC 2011 Ethical allocation of preexposure HIV prophylaxis. JAMA 305 191 192

15. PhillipsANStaszewskiSWeberRKirkOFrancioliP 2001 HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA 286 2560 2567

16. GrahamSMHolteSEPeshuNMRichardsonBAPanteleeffDD 2007 Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS 21 501 507

17. CohenMSChenYQMcCauleyMGambleTHosseinipourMC 2011 Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365 493 505

18. AttiaSEggerMMullerMZwahlenMLowN 2009 Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS 23 1397 1404

19. MontanerJSLimaVDBarriosRYipBWoodE 2010 Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet 376 532 539

20. DonnellDBaetenJMKiarieJThomasKKStevensW 2010 Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 375 2092 2098

21. ReynoldsSJMakumbiFNakigoziGKagaayiJGrayRH 2011 HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy in Rakai, Uganda. AIDS

22. World Health Organization 2009 Antiretroviral therapy for HIV infection in adults and adolescents. Available: http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf. Accessed 17 October 2011

23. CohenMSShawGMMcMichaelAJHaynesBF 2011 Acute HIV-1 infection. N Engl J Med 364 1943 1954

24. PowersKAGhaniACMillerWCHoffmanIFPettiforAE The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study. Lancet 378 256 268

25. HollingsworthTDAndersonRMFraserC 2008 HIV-1 transmission, by stage of infection. J Infect Dis 198 687 693

26. MontanerJSHoggRWoodEKerrTTyndallM 2006 The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet 368 531 536

27. GranichRMGilksCFDyeCDe CockKMWilliamsBG 2008 Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 373 48 57

28. GrantRMLamaJRAndersonPLMcMahanVLiuAY 2010 Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 363 2587 2599

29. Family Health International 2011 FHI to initiate orderly closure of FEM-PrEP Available: http://www.fhi.org/en/Research/Projects/FEM-PrEP.htm. Accessed 17 October 2011

30. The Microbicide Trials Network 2011 MTN statement on decision to discontinue use of oral tenofovir tablets in VOICE, a major HIV prevention study in women. Available: http://www.mtnstopshiv.org/node/3619. Accessed 17 October 2011

31. PaxtonLAHopeTJaffeHW 2007 Pre-exposure prophylaxis for HIV infection: what if it works? Lancet 370 89 93

32. MishraVVaessenMBignami-Van AsscheSHongR 2006 Why do so many HIV-discordant couples in sub-Saharan Africa have female partners infected, not male partners [Abstract 1717]? In: Proceedings of the HIV/AIDS Implementers' Meeting; 16–19 June 2007, 2006; Kigali, Rwanda

33. WalqueDD 2007 Sero-discordant couples in five African countries: implications for prevention strategies. Popul Dev Rev 33 501 523

34. EyawoOde WalqueDFordNGakiiGLesterRT 2010 HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect Dis 10 770 777

35. MatovuJK 2010 Preventing HIV transmission in married and cohabiting HIV-discordant couples in sub-Saharan Africa through combination prevention. Curr HIV Res 8 430 440

36. ChemaitellyHCreminIHallettTBAbu-RaddadL 2011 Patterns of HIV Infection among Stable Sexual Partnerships in sub-Saharan Africa. Sex Transm Infect In press

37. LingappaJRLambdinBBukusiEANgureKKavumaL 2008 Regional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial. PLoS ONE 3 e1411 doi:10.1371/journal.pone.0001411

38. ChimbiriAM 2007 The condom is an ‘intruder’ in marriage: evidence from rural Malawi. Soc Sci Med 64 1102 1115

39. MugoNRHeffronRDonnellDWaldAWereEO Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1 serodiscordant couples. AIDS 25 1887 1895

40. CelumCWaldALingappaJRMagaretASWangRS 2010 Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med 362 427 439

41. LingappaJRKahleEMugoNMujugiraAMagaretA 2009 Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study. PLoS ONE 4 e5272 doi:10.1371/journal.pone.0005272

42. LingappaJRBaetenJMWaldAHughesJPThomasKK 2010 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

43. FideliUSAllenSAMusondaRTraskSHahnBH 2001 Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retroviruses 17 901 910

44. HollingsworthTDLaeyendeckerOShirreffGDonnellyCASerwaddaD 2010 HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda. PLoS Pathog 6 e1000876 doi:10.1371/journal.ppat.1000876

45. StoverJBollingerL The costs of antiretroviral therapy in low and middle income countries: present commitments and future needs. Available: http://www.futureartcosts.org/questions/default.aspx?question=oneperson. Accessed 17 October 2011

46. OverM 2010 Sustaining and leveraging AIDS treatment. Available: http://www.cgdev.org/content/publications/detail/1424173, accessed 13-12-10. Accessed 17 October 2011

47. MenziesNABerrutiAABerzonRFillerSFerrisR 2011 The cost of providing comprehensive HIV treatment in PEPFAR-supported programs. AIDS 25 1753 1760

48. South Africa National AIDS Council 2010 The South Africa antiretroviral treatment guidelines 2010. Available: http://www.doh.gov.za/docs/factsheets/guidelines/art.pdf. Accessed 19 January 2011

49. TengsTOLinTH 2002 A meta-analysis of utility estimates for HIV/AIDS. Med Decis Making 22 475 481

50. BongaartsJOverM 2010 Public health. Global HIV/AIDS policy in transition. Science 328 1359 1360

51. JamisonDTBremanJGMeashamARAlleyneGClaesonM 2006 Disease control priorities in developing countries. Second edition New York, Washington (D.C.) Oxford University Press and The World Bank

52. Organization WH CHOosing Interventions that are Cost Effective (WHO-CHOICE). Available: http://www.who.int/choice/en/. Accessed 17 October 2011

53. HastingsA 2011 Estimates of costs of delivering pre-exposure prophylaxis in South Africa. Available: https://wwwsugarsynccom/pf/D666097_644757_928835. Accessed 17 October 2011

54. Meyer-RathGBrennanALongLRosenSPillayY 2010 Total cost and potential cost savings of the national antiretroviral treatment (ART) programme in South Africa 2010 to 2017 [Abstract WEAE0201] In: Proceedings of the XVIII International AIDS Conference; 18–23 July 2010. Vienna, Austria

55. BunnellREkwaruJPSolbergPWamaiNBikaako-KajuraW 2006 Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda. AIDS 20 85 92

56. AllenSMeinzen-DerrJKautzmanMZuluITraskS 2003 Sexual behavior of HIV discordant couples after HIV counseling and testing. AIDS 17 733 740

57. United Nations General Assembly 2011 Political declaration on HIV/AIDS: intensifying our efforts to eliminate HIV/AIDS. Available: http://daccess-dds-ny.un.org/doc/UNDOC/LTD/N11/367/84/PDF/N1136784.pdf?OpenElement. Accessed 17 October 2011

58. van de VijverDADerdelinckxIBoucherCA 2009 Circulating HIV type 1 drug resistance will have limited impact on the effectiveness of preexposure prophylaxis among young women in Zimbabwe. J Infect Dis 199 1310 1317

59. SupervieVGarcia-LermaJGHeneineWBlowerS 2010 HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis. Proc Natl Acad Sci U S A 107 12381 12386

60. RottingenJACameronDWGarnettGP 2001 A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known? Sex Transm Dis 28 579 597

61. GarnettGP 2002 An introduction to mathematical models in sexually transmitted disease epidemiology. Sex Transm Infect 78 7 12

62. DoddPJGarnettGPHallettTB 2010 Examining the promise of HIV elimination by ‘test and treat’ in hyperendemic settings. AIDS 24 729 735

63. PretoriusCStoverJBollingerLBacaerNWilliamsB 2010 Evaluating the cost-effectiveness of pre-exposure prophylaxis (PrEP) and its impact on HIV-1 transmission in South Africa. PLoS ONE 5 e13646 doi:10.1371/journal.pone.0013646

64. WilliamsBGDyeC 2003 Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS. Science 301 1535 1537

65. BaggaleyRFWhiteRGBoilyMC 2010 HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol 39 1048 1063

66. eligibility for ART in lower income countries collaboration 2008 Duration from seroconversion to eligibility for antiretroviral therapy and from ART eligibility to death in adult HIV-infected patients from low and middle-income countries: collaborative analysis of prospective studies. Sex Transm Infect 84 i31 i36

67. KitahataMMGangeSJAbrahamAGMerrimanBSaagMS 2009 Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 360 1815 1826

68. EtardJFNdiayeIThierry-MiegMGueyeNFGueyePM 2006 Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study. AIDS 20 1181 1189

69. MahyMLewdenCBrinkhofMWDabisFTassieJM 2010 Derivation of parameters used in Spectrum for eligibility for antiretroviral therapy and survival on antiretroviral therapy. Sex Transm Infect 86 Suppl 2 ii28 ii34

70. StringerJSAZuluILevyJStringerEMMwangoA 2006 Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 296 782 793