Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

English version České info

Background:
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.

Methods and Findings:
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.

Conclusions:
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.

Please see later in the article for the Editors' Summary

Vyšlo v časopise: Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies. PLoS Med 11(9): e32767. doi:10.1371/journal.pmed.1001718
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001718

Souhrn

Zdroje

1. BekkerLG, OrrellC, ReaderL, MatotiK, CohenK, et al. (2003) Antiretroviral therapy in a community clinic–early lessons from a pilot project. S Afr Med J 93: 458–462.

2. CoetzeeD, HildebrandK, BoulleA, MaartensG, LouisF, et al. (2004) Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 18: 887–895.

3. WesterCW, KimS, BussmannH, AvalosA, NdwapiN, et al. (2005) Initial response to highly active antiretroviral therapy in HIV-1C-infected adults in a public sector treatment program in Botswana. JAIDS 40: 336–343.

4. StringerJS, ZuluI, LevyJ, StringerEM, MwangoA, et al. (2006) Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 296: 782–793.

5. ToureS, KouadioB, SeylerC, TraoreM, Dakoury-DogboN, et al. (2008) Rapid scaling-up of antiretroviral therapy in 10000 adults in Cote d'Ivoire: 2-year outcomes and determinants. AIDS 22: 873–882.

6. Bradshaw D, Dorrington RE, Laubscher R (2012) Rapid mortality surveillance report 2011. Cape Town: South African Medical Research Council.

7. MayM, SterneJA, SabinC, CostagliolaD, JusticeAC, et al. (2007) Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS 21: 1185–1197.

8. BrinkhofMW, SpycherBD, YiannoutsosC, WeigelR, WoodR, et al. (2010) Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa. PLoS ONE 5: e14149.

9. BraitsteinP, BrinkhofMW, DabisF, SchechterM, BoulleA, et al. (2006) Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 367: 817–824.

10. KeiserO, OrrellC, EggerM, WoodR, BrinkhofMW, et al. (2008) Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared. PLoS Med 5: e148.

11. 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.

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

13. MayMT, HoggRS, JusticeAC, ShepherdBE, CostagliolaD, et al. (2012) Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics. Int J Epidemiol 41: 1807–1820.

14. ShepherdBE, SterlingTR, MooreRD, RaffantiSP, HulganT (2009) Cross-cohort heterogeneity encountered while validating a model for HIV disease progression among antiretroviral initiators. J Clin Epidemiol 62: 729–737.

15. 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.

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

17. MayMT, IngleSM, CostagliolaD, JusticeAC, de WolfF, et al. (2014) Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC). Int J Epidemiol 43: 691–702.

18. KeiserO, OrrellC, EggerM, WoodR, BrinkhofMW, et al. (2008) Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared. PLoS Med 5: e148.

19. CoetzeeD, HilderbrandK, BoulleA, DraperB, AbdullahF, et al. (2005) Effectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa. Bull World Health Organ 83: 489–494.

20. IngleSM, MayM, GillCJ, MugaveroM, LewdenC, et al. (2014) Impact of risk factors for specific causes death in the first and subsequent years of ART among HIV-infected patients. Clin Infect Dis 59: 287–297.

21. UNAIDS (2010) UNAIDS Report on the Global AIDS Epidemic. Geneva: UNAIDS.

22. CaseKK, GhysPD, GouwsE, EatonJW, BorquezA, et al. (2012) Understanding the modes of transmission model of new HIV infection and its use in prevention planning. Bull World Health Organ 90: 831–838A.

23. WhiteIR, RoystonP, WoodAM (2011) Multiple imputation using chained equations: Issues and guidance for practice. Stat Med 30: 377–399.

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

25. SchomakerM, GsponerT, EstillJ, FoxM, BoulleA (2013) Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment. Stat Med 33: 129–142.

26. LanoyE, LewdenC, LievreL, TattevinP, BoileauJ, et al. (2009) How does loss to follow-up influence cohort findings on HIV infection? A joint analysis of the French hospital database on HIV, Mortalite 2000 survey and death certificates. HIV Med 10: 236–245.

27. Institute for Health Metrics and Evaluation (2010) Global Burden of Disease Study 2010. Mortality Results 1970–2010. Seattle: Institute for Health Metrics and Evaluation (IHME).

28. GrimsrudAT, CornellM, EggerM, BoulleA, MyerL (2013) Impact of definitions of loss to follow-up (LTFU) in antiretroviral therapy program evaluation: variation in the definition can have an appreciable impact on estimated proportions of LTFU. J Clin Epidemiol 66: 1006–1013.

29. ShepherdBE, BlevinsM, VazLM, MoonTD, KippAM, et al. (2013) Impact of definitions of loss to follow-up on estimates of retention, disease progression, and mortality: application to an HIV program in Mozambique. Am J Epidemiol 178: 819–828.

30. CornellM, SchomakerM, GaroneDB, GiddyJ, HoffmannCJ, et al. (2012) Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study. PLoS Med 9: e1001304.

31. JohnsonLF, MossongJ, DorringtonRE, SchomakerM, HoffmannCJ, et al. (2013) Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Med 10: e1001418.

32. EggerM, SpycherBD, SidleJ, WeigelR, GengEH, et al. (2011) Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa. PLoS Med 8: e1000390.

33. CornellM, GrimsrudA, FairallL, FoxMP, 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.

34. AlthoffKN, RebeiroP, BrooksJT, BuchaczK, GeboK, et al. (2014) Disparities in the quality of HIV care when using US Department of Health and Human Services indicators. Clin Infect Dis 58: 1185–1189.

35. HannaDB, BuchaczK, GeboKA, HessolNA, HorbergMA, et al. (2013) Trends and disparities in antiretroviral therapy initiation and virologic suppression among newly treatment-eligible HIV-infected individuals in North America, 2001–2009. Clin Infect Dis 56: 1174–1182.

36. JarvisJN, GovenderN, ChillerT, ParkBJ, LongleyN, et al. (2012) Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: a proposed algorithm for clinical implementation. J Int Assoc Physicians AIDS Care (Chic) 11: 374–379.

37. MartinsonNA, KarstaedtA, VenterWF, OmarT, KingP, et al. (2007) Causes of death in hospitalized adults with a premortem diagnosis of tuberculosis: an autopsy study. AIDS 21: 2043–2050.

38. BassettIV, WangB, ChettyS, GiddyJ, LosinaE, et al. (2010) Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis 51: 823–829.

39. CastelnuovoB, ManabeYC, KiraggaA, KamyaM, EasterbrookP, et al. (2009) Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis 49: 965–972.

40. WongEB, OmarT, SetlhakoGJ, OsihR, FeldmanC, et al. (2012) Causes of death on antiretroviral therapy: a post-mortem study from South Africa. PLoS ONE 7: e47542.

41. MannB, MilloyMJ, KerrT, ZhangR, MontanerJ, et al. (2012) Improved adherence to modern antiretroviral therapy among HIV-infected injecting drug users. HIV Med 13: 596–601.

42. RasmussenLD, OmlandLH, PedersenC, GerstoftJ, KronborgG, et al. (2010) Risk of myocardial infarction in parents of HIV-infected Individuals: a population-based Cohort Study. BMC Infect Dis 10: 169.

43. ObelN, OmlandLH, KronborgG, LarsenCS, PedersenC, et al. (2011) Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study. PLoS ONE 6: e22698.

44. ChenTY, DingEL, Seage IiiGR, KimAY (2009) Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression. Clin Infect Dis 49: 1605–1615.