The Effect of Highly Active Antiretroviral Therapy on the Survival of HIV-Infected Children in a Resource-Deprived Setting: A Cohort Study

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Background:
The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting.

Methods and Findings:
Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4–4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1–8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06–0.95).

Conclusions:
HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States.

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

Vyšlo v časopise: The Effect of Highly Active Antiretroviral Therapy on the Survival of HIV-Infected Children in a Resource-Deprived Setting: A Cohort Study. PLoS Med 8(6): e32767. doi:10.1371/journal.pmed.1001044
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001044

Souhrn

Zdroje

1. Panel on Antiretroviral Guidelines for Adults and Adolescents 2009 Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington (District of Columbia) Department of Health and Human Services Available: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 1 October 2010

2. ThompsonMAAbergJACahnPMontanerJSRizzardiniG 2010 Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA 304 321 333

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

4. SterneJAMayMCostagliolaDde WolfFPhillipsAN 2009 Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 373 1352 1363

5. KourtisAPIbegbuCNahmiasAJLeeFKClarkWS 1996 Early progression of disease in HIV-infected infants with thymus dysfunction. N Engl J Med 335 1431 1436

6. ShearerWTQuinnTCLaRussaPLewJFMofensonL 1997 Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group. N Engl J Med 336 1337 1342

7. NewellMLCoovadiaHCortina-BorjaMRollinsNGaillardP 2004 Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 364 1236 1243

8. LindseyJCHughesMDMcKinneyRECowlesMKEnglundJA 2000 Treatment-mediated changes in human immunodeficiency virus (HIV) type 1 RNA and CD4 cell counts as predictors of weight growth failure, cognitive decline, and survival in HIV-infected children. J Infect Dis 182 1385 1393

9. Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group 2008 Response to combination antiretroviral therapy: variation by age. AIDS 22 1463 1473

10. Joint United Nations Programme on HIV/AIDS 2008 2008 Report on the global HIV/AIDS epidemic. Geneva Joint United Nations Programme on HIV/AIDS

11. de MartinoMTovoPABalducciMGalliLGabianoC 2000 Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. JAMA 284 190 197

12. PatelKHernánMAWilliamsPLSeegerJDMcIntoshK 2008 Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. Clin Infect Dis 46 507 515

13. World Health Organization, Joint United Nations Programme on HIV/AIDS, and United Nations Children's Fund 2009 Towards universal access: scaling up priority HIV/AIDS interventions in the health sector: progress report 2009. Geneva World Health Organization

14. BeckEWalenskyR 2008 The outcome and impact of ten years of HAART. WhitesideAGhazianiAZunigaJMBartlettJG A decade of HAART: the development and global impact of highly active antiretroviral therapy Oxford Oxford University Press 45 63

15. BraitsteinPBrinkhofMWDabisFSchechterMBoulleA 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

16. KeiserOOrrellCEggerMWoodRBrinkhofMW 2008 Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared. PLoS Med 5 e148 doi:10.1371/journal.pmed.0050148

17. Bolton-MooreCMubiana-MbeweMCantrellRAChintuNStringerEM 2007 Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA 298 1888 1899

18. GeorgeENoelFBoisGCassagnolREstavienL 2007 Antiretroviral therapy for HIV-1-infected children in Haiti. J Infect Dis 195 1411 1418

19. FassinouPElengaNRouetFLaguideRKouakoussuiKA 2004 Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Cote d'Ivoire. AIDS 18 1905 1913

20. KIDS-ART-LINC Collaboration 2008 Low risk of death, but substantial program attrition, in pediatric HIV treatment cohorts in sub-Saharan Africa. J Acquir Immune Defic Syndr 49 523 531

21. FennerLBrinkhofMWKeiserOWeigelRCornellM 2010 Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa. J Acquir Immune Defic Syndr 54 524 532

22. McConnellMSChasombatSSiangphoeUYuktanontPLolekhaR 2010 National program scale-up and patient outcomes in a pediatric antiretroviral treatment program, Thailand, 2000-2007. J Acquir Immune Defic Syndr 54 423 429

23. SutcliffeCGvan DijkJHBolton-MooreCCothamMTambatambaB 2010 Differences in presentation, treatment initiation, and response among children infected with human immunodeficiency virus in urban and rural Zambia. Pediatr Infect Dis J 29 849 854

24. AnakyMFDuvignacJWeminLKouakoussuiAKarcherS 2010 Scaling up antiretroviral therapy for HIV-infected children in Cote d'Ivoire: determinants of survival and loss to programme. Bull World Health Organ 88 490 499

25. LeyenaarJKNovosadPMFerrerKTThahaneLKMohapiEQ 2010 Early clinical outcomes in children enrolled in human immunodeficiency virus infection care and treatment in Lesotho. Pediatr Infect Dis J 29 340 345

26. EdmondsALusiamaJNapravnikSKiteteleFVan RieA 2009 Anti-retroviral therapy reduces incident tuberculosis in HIV-infected children. Int J Epidemiol 38 1612 1621

27. World Health Organization 2006 Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach—2006 revision. Geneva World Health Organization

28. World Health Organization 2010 Antiretroviral therapy for HIV infection in infants and children: recommendations for a public health approach—2010 revision. Geneva World Health Organization

29. National Program for the Fight against AIDS 2005 National guide for antiretroviral treatment of HIV infection. Kinshasa Democratic Republic of the Congo Ministry of Health

30. ColeSRHernánMAMargolickJBCohenMHRobinsJM 2005 Marginal structural models for estimating the effect of highly active antiretroviral therapy initiation on CD4 cell count. Am J Epidemiol 162 471 478

31. RobinsJMHernánMABrumbackB 2000 Marginal structural models and causal inference in epidemiology. Epidemiology 11 550 560

32. FewellZHernánMAWolfeFTillingKChoiH 2004 Controlling for time-dependent confounding using marginal structural models. Stata J 4 402 420

33. HernánMABrumbackBRobinsJM 2000 Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 11 561 570

34. HernánMAMcAdamsMMcGrathNLanoyECostagliolaD 2009 Observation plans in longitudinal studies with time-varying treatments. Stat Methods Med Res 18 27 52

35. WestreichDColeSRTienPCChmielJSKingsleyL 2010 Time scale and adjusted survival curves for marginal structural cox models. Am J Epidemiol 171 691 700

36. GreenlandSPearlJRobinsJM 1999 Causal diagrams for epidemiologic research. Epidemiology 10 37 48

37. CoghlanBBrennanRJNgoyPDofaraDOttoB 2006 Mortality in the Democratic Republic of Congo: a nationwide survey. Lancet 367 44 51

38. HIV-CAUSAL Collaboration 2010 The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS 24 123 137

39. FairallLRBachmannMOLouwagieGMvan VuurenCChikobvuP 2008 Effectiveness of antiretroviral treatment in a South African program: a cohort study. Arch Intern Med 168 86 93

40. De BaetsAJRametJMsellatiPLepageP 2008 The unique features of pediatric HIV-1 in sub-Saharan Africa. Curr HIV Res 6 351 362

41. RaitenDJGrinspoonSArpadiS 2005 Nutritional considerations in the use of ART in resource-limited settings. Geneva World Health Organization Department of Nutrition for Health and Development

42. FetzerBCHosseinipourMCKamthuziPHydeLBramsonB 2009 Predictors for mortality and loss to follow-up among children receiving anti-retroviral therapy in Lilongwe, Malawi. Trop Med Int Health 14 862 869

43. FlysTNissleyDVClaasenCWJonesDShiC 2005 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 192 24 29

44. EshlemanSHMracnaMGuayLADeseyveMCunninghamS 2001 Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS 15 1951 1957