#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study


Background:
Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.

Methods and Findings:
Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.

Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions:
HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.



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


Vyšlo v časopise: Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study. PLoS Med 9(9): e32767. doi:10.1371/journal.pmed.1001304
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001304

Souhrn

Background:
Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.

Methods and Findings:
Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.

Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions:
HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.



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


Zdroje

1. JohnsonL (2012) Access to antiretroviral treatment in South Africa, 2004–2011. S Afr J HIV Med 13: 22–27.

2. BraitsteinP, BoulleA, NashD, BrinkhofM, DabisF, et al. (2008) Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration. J Womens Health (Larchmt) 17: 47–55.

3. MuulaA, NgulubeT, SiziyaS, MakupeC, UmarE, et al. (2007) Gender distribution of adult patients on highly active antiretroviral therapy (HAART) in Southern Africa: a systematic review. BMC Public Health 7: 63.

4. StenehjemE, ShlayJC (2008) Sex-specific differences in treatment outcomes for patients with HIV and AIDS. Expert Rev Pharmacoecon Outcomes Res 8: 51–63.

5. HawkinsC, ChalamillaG, OkumaJ, SpiegelmanD, HertzmarkE, et al. (2011) Gender differences in antiretroviral treatment outcomes among HIV-infected adults in Dar es Salaam, Tanzania. AIDS 25: 1189–1197.

6. StringerJSA, ZuluI, LevyJ, StringerEM, MwangoA, et al. (2006) Rapid scale-up of antiretroviral therapy at primary care sites in Zambia. JAMA 296: 782–793.

7. KlausnerJ, SerenataC, O'BraH, MattsonC, BrownJ, et al. (2011) Scale-up and continuation of antiretroviral therapy in South African treatment programs, 2005–2009. J Acquir Immune Defic Syndr 56: 292–295.

8. Taylor-SmithK, TweyaH, HarriesA, SchouteneE, JahnA (2010) Gender differences in retention and survival on antiretroviral therapy of HIV-1 infected adults in Malawi. Malawi Med J 22: 49–56.

9. BrinkhofM, DabisF, MyerL, BangsbergDR, BoulleA, et al. (2008) Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries. Bull World Health Organ 86: 559–567.

10. HoggRS, YipB, ChanKJ, WoodE, CraibKJ, et al. (2001) Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA 286: 2568–2577.

11. LawnSD, HarriesAD, AnglaretX, MyerL, WoodR (2008) Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 22: 1897–1908.

12. CornellM, GrimsrudA, FairallL, FoxM, van CutsemG, et al. (2010) Temporal changes in programme outcomes among adult patients initiating antiretroviral therapy across South Africa, 2002–2007. AIDS 24: 2263–2270.

13. BrinkhofMWG, Pujades-RodriguezM, EggerM (2009) Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis. PLoS One 4: e5790 doi:10.1371/journal.pone.0005790.

14. Ochieng-OokoV, OchiengD, SidleJ, HoldsworthM, Wools-KaloustianK, et al. (2010) Influence of gender on loss to follow-up in a large HIV treatment programme in western Kenya. Bull World Health Organ 88: 681–688.

15. NglaziM, LawnS, KaplanR, KranzerK, OrrellC, et al. (2011) Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa. J Acquir Immune Defic Syndr 56: 1e1–e8.

16. CornellM, TechnauK, FairallL, WoodR, MoultrieH, et al. (2009) Monitoring the South African National Antiretroviral Treatment Programme, 2003–2007: the IeDEA Southern Africa collaboration. S Afr Med J 99: 653–660.

17. EggerM, EkoueviD, WilliamsC, LyamuyaR, MukumbiH, et al. (2011) Cohort Profile: The international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa. Int J Epidemiol 1–9.

18. MayM, BoulleA, PhiriS, MessouE, MyerL, et al. (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.

19. Van CutsemG, FordN, HildebrandK, GoemaereE, MatheeS, et al. (2011) Correcting for mortality among patients lost to follow up on antiretroviral therapy in South Africa: a cohort analysis. PLoS One 6: e14684 doi:10.1371/journal.pone.0014684.

20. RubinD (1996) Multiple imputation after 18+ years. J Am Stat Assoc 91: 473–489.

21. van BuurenS, BoshuizenHC, KnookDL (1999) Multiple imputation of missing blood pressure covariates in survival analysis. Stat Med 18: 681–694.

22. BoulleA, Van CutsemG, HilderbrandK, CraggC, AbrahamsM, et al. (2010) Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 24: 563–572.

23. Actuarial Society of South Africa (2011) ASSA 2008 AIDS and Demographic Model (lite version 110207). Available: http://aids.actuarialsociety.org.za/ASSA2008-Model-3480.htm

24. KullerLH (1999) Invited commentary: circular epidemiology. Am J Epidemio 150: 897–903.

25. JohannessenA (2011) Are men the losers of the antiretroviral treatment scale-up? AIDS 25: 1225–1226.

26. MillsE, BakandaC, BirungiJ, ChanK, HoggR, et al. (2011) Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda. J Int AIDS Soc 14: 52.

27. Wools-KaloustianK, KimaiyoS, DieroL, SiikaA, SidleJ, et al. (2006) Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya. AIDS 20: 41–48.

28. MontanerJSG, HoggR, WoodE, KerrT, TyndallM, et al. (2006) The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet 368: 531–536.

29. OjikutuB, ZhengH, WalenskyR, LuZ, LosinaE, et al. (2008) Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa. S Afr Med J 98: 204–208.

30. RussellE, CharalambousS, PembaL, ChurchyardGJ, GrantA, et al. (2010) Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study. BMC Public Health 10: 433.

31. ZachariahR, HarriesK, MosesM, ManziM, LineA, et al. (2009) Very early mortality in patients starting antiretroviral treatment at primary health centres in rural Malawi. Trop Med Int Health 14: 713–721.

32. CornellM, McIntyreJ, MyerL (2011) Men and antiretroviral therapy in Africa: our blind spot. Trop Med Int Health 828–829.

33. HawkesS, HartG (2000) Men's sexual health matters: promoting reproductive health in an international context. Trop Med Int Health 5: A37–44.

34. KalmussD, TatumC (2007) Patterns of men's use of sexual and reproductive health services. Perspect Sex Reprod Health 39: 74–81.

35. SternbergP, HubleyJ (2004) Evaluating men's involvement as a strategy in sexual and reproductive health promotion. Health Promot Int 19: 389–396.

36. BrinkhofMWG, BoulleA, WeigelR, MessouE, MathersC, et al. (2009) Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality. PLoS Med 6: e1000066 doi:10.1371/journal.pmed.1000066.

37. McGuireM, MunyenyembeT, SzumilinE, HeinzelmannA, Le PaihM, et al. (2010) Vital status of pre-ART and ART patients defaulting from care in rural Malawi. Trop Med Int Health 15: 55–62.

38. TweyaH, GaretaD, ChagweraF, Ben-SmithA, MwenyemasiJ, et al. (2010) Early active follow-up of patients on antiretroviral therapy (ART) who are lost to follow-up: the ‘Back-to-Care’ project in Lilongwe, Malawi. Trop Med Int Health 15: 82–89.

39. WeigelR, HochgesangM, BrinkhofMW, HosseinipourM, BoxshallM, et al. (2011) Outcomes and associated risk factors of patients traced after being lost to follow-up from antiretroviral treatment in Lilongwe, Malawi. BMC Infect Dis 11: 31.

40. YuJ, ChenS-C, WangK-Y, ChangC-S, MakombeS, et al. (2007) True outcomes for patients on antiretroviral therapy who are ‘lost to follow-up’ in Malawi. Bull World Health Organ 85: 550–554.

41. NachegaJB, HislopM, DowdyDW, LoM, OmerSB, et al. (2006) Adherence to highly active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South African Adults. J Acquir Immune Defic Syndr 43: 78–84.

42. MamanD, Pujades-RodriguezM, SubtilF, PinogesL, McGuireM, et al. (2012) Gender differences in immune reconstitution: a multicentric cohort analysis in sub-Saharan Africa. PLoS One 7: e31078 doi:10.1371/journal.pone.0031078.

43. NashD, KatyalM, BrinkhofMWG, KeiserO, MayM, et al. (2008) Long-term immunologic response to antiretroviral therapy in low-income countries: collaborative analysis of prospective studies. AIDS 22: 2291–2302.

44. BlackerJ (2004) The impact of AIDS on adult mortality: evidence from national and regional statistics. AIDS 18: S19–S26.

45. CaseA, PaxsonC (2005) Sex differences in morbidity and mortality. Demography 42: 189–214.

46. OwensIPF (2002) Sex differences in mortality rate. Science 297: 2008–2009.

47. RajaratnamJK, MarcusJR, Levin-RectorA, ChalupkaAN, WangH, et al. (2010) Worldwide mortality in men and women aged 15–59 years from 1970 to 2010: a systematic analysis. Lancet 375: 1704–1720.

48. RigbyJE, DorlingD (2007) Mortality in relation to sex in the affluent world. J Epidemiol Commun Health 61: 159–164.

49. NormanR, MatzopoulosR, GroenewaldP, BradshawD (2007) The high burden of injuries in South Africa. Bull World Health Organ 85: 695–702.

50. HillK, LopezAD, ShibuyaK, JhaP (2007) Interim measures for meeting needs for health sector data: births, deaths, and causes of death. Lancet 370: 1726–1735.

51. Jamison D, Feachem R, Makgoba M, Bos E, Baingana F, et al. (2006) Disease and mortality in sub-Saharan Africa, 2nd edition. Washington (D.C.): World Bank.

52. Bradshaw D, Timaeus I (2006) Levels and trends of adult mortality. Jamison D, Feachem R, Makgoba Mea, editors. Disease and mortality in sub-Saharan Africa. Washington (D.C.): World Bank.

53. Dorrington R, Bourne D, Bradshaw D, Laubscher R, Timaeus I (2001) The impact of HIV/AIDS on adult mortality in South Africa. Cape Town: Burden of Disease Research Unit, Medical Research Council.

54. BassettI, ChettyS, WangB, MazibukoM, GiddyJ, et al. (2012) Loss to follow-up and mortality among HIV-infected people co-infected with TB at ART initiation in Durban, South Africa. J Acquir Immune Defic Syndr 59: 25–30.

Štítky
Interné lekárstvo

Článok vyšiel v časopise

PLOS Medicine


2012 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#