Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

English version České info

Background:
Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.

Methods and Findings:
PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.

: Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).

Conclusions:
Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.

Review Registration:
International Prospective Register of Systematic Reviews CRD42011001209

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

Vyšlo v časopise: Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis. PLoS Med 9(7): e32767. doi:10.1371/journal.pmed.1001270
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001270

Souhrn

Review Registration:
International Prospective Register of Systematic Reviews CRD42011001209

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

Zdroje

1. HarriesAD, ZachariahR, CorbettEL, LawnSD, Santos-FilhoET, et al. (2010) The HIV-associated tuberculosis epidemic—when will we act? Lancet 375: 1906–1919.

2. Joint United Nations Programme on HIV/AIDS (2011) World AIDS Day report 2011. Available: http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/JC2216_WorldAIDSday_report_2011_en.pdf. Accessed 23 November 2011.

3. World Health Organization (2011) Global tuberculosis control 2011. Available: http://www.who.int/entity/tb/publications/global_report/2011/gtbr11_full.pdf. Accessed 14 October 2011.

4. The United Nations (2011) The Millenium Development Goals report. Available: http://mdgs.un.org/unsd/mdg/Resources/Static/Products/Progress2011/11-31339%20(E)%20MDG%20Report%202011_Book%20LR.pdf. Accessed 18 July 2011.

5. Stop TB Partnership (2010) The global plan to stop TB: 2011–2015. Available: http://www.stoptb.org/assets/documents/global/plan/TB_GlobalPlanToStopTB2011-2015.pdf. Accessed 7 February 2011.

6. BorgdorffMW, FloydK, BroekmansJF (2002) Interventions to reduce tuberculosis mortality and transmission in low- and middle-income countries. Bull World Health Organ 80: 217–227.

7. Abu-RaddadLJ, SabatelliL, AchterbergJT, SugimotoJD, LonginiIMJr, et al. (2009) Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics. Proc Natl Acad Sci U S A 106: 13980–13985.

8. LonnrothK, CastroKG, ChakayaJM, ChauhanLS, FloydK, et al. (2010) Tuberculosis control and elimination 2010–50: cure, care, and social development. Lancet 375: 1814–1829.

9. De CockKM, ChaissonRE (1999) Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection. Int J Tuberc Lung Dis 3: 457–465.

10. World Health Organization (2012) WHO policy on collaborative TB/HIV activities: guidelines for national programmes and other stakeholders. Available: http://whqlibdoc.who.int/publications/2012/9789241503006_eng.pdf. Accessed 12 March 2012.

11. World Health Organization (2011) Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Available: http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf. Accessed 11 April 2011.

12. World Health Organization (2009) WHO policy on TB infection control in health-care facilities, congregate settings, and households. Available: http://whqlibdoc.who.int/publications/2009/9789241598323_eng.pdf. Accessed 10 September 2010.

13. LawnSD, WoodR, De CockKM, KranzerK, LewisJJ, et al. (2010) Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources. Lancet Infect Dis 10: 489–498.

14. World Health Organization (2010) Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. Available: http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. Accessed 11 April 2011.

15. WilliamsBG, GranichR, De CockKM, GlaziouP, SharmaA, et al. (2010) Antiretroviral therapy for tuberculosis control in nine African countries. Proc Natl Acad Sci U S A 107: 19485–19489.

16. LawnSD, HarriesAD, WilliamsBG, ChaissonRE, LosinaE, et al. (2011) Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? Int J Tuberc Lung Dis 15: 571–581.

17. World Health Organization (2012 June) Programmatic update: antiretroviral therapy as prevention (TasP) of HIV and TB. Available: http://whqlibdoc.who.int/hq/2012/WHO_HIV_2012.12_eng.pdf. Accessed 25 June 2012.

18. LiberatiA, AltmanDG, TetzlaffJ, MulrowC, GotzschePC, et al. (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6: e1000100 doi:10.1371/journal.pmed.1000100.

19. Suthar AB (2011) Antiretroviral therapy for prevention of HIV-associated tuberculosis: a systematic review and meta-analysis. PROSPERO. Available: http://www.crd.york.ac.uk/PROSPEROFILES/1209_PROTOCOL.pdf. Accessed 22 June 2012.

20. LawnSD, MyerL, EdwardsD, BekkerLG, WoodR (2009) Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS 23: 1717–1725.

21. Van RieA, WestreichD, SanneI (2011) Tuberculosis in patients receiving antiretroviral treatment: incidence, risk factors, and prevention strategies. J Acquir Immune Defic Syndr 56: 349–355.

22. GirardiE, SabinCA, d'Arminio MonforteA, HoggB, PhillipsAN, et al. (2005) Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America. Clin Infect Dis 41: 1772–1782.

23. SterlingTR, LauB, ZhangJ, FreemanA, BoschRJ, et al. (2011) Risk factors for tuberculosis after highly active antiretroviral therapy initiation in the United States and Canada: implications for tuberculosis screening. J Infect Dis 204: 893–901.

24. DembeleM, SaleriN, CarvalhoAC, SaouadogoT, HienAD, et al. (2010) Incidence of tuberculosis after HAART initiation in a cohort of HIV-positive patients in Burkina Faso. Int J Tuberc Lung Dis 14: 318–323.

25. LawnSD, KranzerK, EdwardsDJ, McNallyM, BekkerLG, et al. (2010) Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS 24: 1323–1328.

26. DyeC, WilliamsBG (2010) The population dynamics and control of tuberculosis. Science 328: 856–861.

27. DyeC, LonnrothK, JaramilloE, WilliamsBG, RaviglioneM (2009) Trends in tuberculosis incidence and their determinants in 134 countries. Bull World Health Organ 87: 683–691.

28. The United Nations Development Programme (2011) Human development report. sustainability and equity: a better future for all. Available: http://hdr.undp.org/en/media/HDR_2011_EN_Complete.pdf. Accessed 14 March 2012.

29. The Cochrane Collaboration (2011) Cochrane handbook for systematic reviews of interventions. Available: http://www.cochrane-handbook.org/. Accessed 19 April 2011.

30. Wells G, Shea B, O'Connell D, Peterson J, Welch V, et al. (2011) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 23 February 2011.

31. HanrahanCF, GolubJE, MohapiL, TshabanguN, ModisenyaneT, et al. (2010) Body mass index and risk of tuberculosis and death. AIDS 24: 1501–1508.

32. SeylerC, ToureS, MessouE, BonardD, GabillardD, et al. (2005) Risk factors for active tuberculosis after antiretroviral treatment initiation in Abidjan. Am J Respir Crit Care Med 172: 123–127.

33. NakanjakoD, Mayanja-KizzaH, OumaJ, WanyenzeR, MwesigireD, et al. (2010) Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda. Int J Tuberc Lung Dis 14: 1621–1628.

34. LonnrothK, WilliamsBG, CegielskiP, DyeC (2010) A consistent log-linear relationship between tuberculosis incidence and body mass index. Int J Epidemiol 39: 149–155.

35. GilksCF, CrowleyS, EkpiniR, GoveS, PerriensJ, et al. (2006) The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 368: 505–510.

36. WilliamsBG, KorenrompEL, GouwsE, SchmidGP, AuvertB, et al. (2006) HIV infection, antiretroviral therapy, and CD4+ cell count distributions in African populations. J Infect Dis 194: 1450–1458.

37. KorenrompEL, WilliamsBG, SchmidGP, DyeC (2009) Clinical prognostic value of RNA viral load and CD4 cell counts during untreated HIV-1 infection—a quantitative review. PLoS ONE 4: e5950 doi:10.1371/journal.pone.0005950.

38. WandelS, EggerM, RangsinR, NelsonKE, CostelloC, et al. (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 (Suppl 1) i31–i36.

39. Cooper H, Hedges L (1994) The handbook of research synthesis. New York: Russell Sage Foundation.

40. HigginsJP, ThompsonSG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539–1558.

41. HigginsJP, ThompsonSG, DeeksJJ, AltmanDG (2003) Measuring inconsistency in meta-analyses. BMJ 327: 557–560.

42. BadriM, WilsonD, WoodR (2002) Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet 359: 2059–2064.

43. CohenMS, ChenYQ, McCauleyM, GambleT, HosseinipourMC, et al. (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365: 493–505.

44. GolubJE, PronykP, MohapiL, ThsabanguN, MoshabelaM, et al. (2009) Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS 23: 631–636.

45. GolubJE, SaraceniV, CavalcanteSC, PachecoAG, MoultonLH, et al. (2007) The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS 21: 1441–1448.

46. JereneD, NaessA, LindtjornB (2006) Antiretroviral therapy at a district hospital in Ethiopia prevents death and tuberculosis in a cohort of HIV patients. AIDS Res Ther 3: 10.

47. LannoyLH, Cortez-EscalanteJJ, Evangelista MdoS, RomeroGA (2008) Tuberculosis incidence and risk factors among patients living with HIV/AIDS in public health service institutions in Brasilia, Federal District. Rev Soc Bras Med Trop 41: 549–555.

48. MirandaA, MorganM, JamalL, LasersonK, BarreiraD, et al. (2007) Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995–2001. PLoS ONE 2: e826 doi:10.1371/journal.pone.0000826.

49. SamandariT, AgizewTB, NyirendaS, TedlaZ, SibandaT, et al. (2011) 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet 377: 1588–1598.

50. Santoro-LopesG, de PinhoAM, HarrisonLH, SchechterM (2002) Reduced risk of tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clin Infect Dis 34: 543–546.

51. SevereP, JusteMA, AmbroiseA, EliacinL, MarchandC, et al. (2010) Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 363: 257–265.

52. ZhouJ, ElliottJ, LiPC, LimPL, KiertiburanakulS, et al. (2009) Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database. BMC Infect Dis 9: 46.

53. MoultonLH, GolubJE, DurovniB, CavalcanteSC, PachecoAG, et al. (2007) Statistical design of THRio: a phased implementation clinic-randomized study of a tuberculosis preventive therapy intervention. Clin Trials 4: 190–199.

54. French National Agency for Research on AIDS and Viral Hepatitis (2007) Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults (ANRS 12136 TEMPRANO). Available: http://clinicaltrials.gov/ct2/show/NCT00495651. Accessed 5 August 2011.

55. University of Minnesota Clinical and Translational Science Institute (2009) Strategic timing of antiretroviral treatment (START). Available: http://clinicaltrials.gov/ct2/show/NCT00867048. Accessed 5 August 2011.

56. University of Cape Town (2007) Isoniazid plus (highly active antiretroviral therapy) HAART to prevent tuberculosis (TB) in HIV-infected persons (HAART-IPT). Available: http://clinicaltrials.gov/ct2/show/NCT00463086. Accessed 5 August 2011.

57. BrinkhofMW, EggerM, BoulleA, MayM, HosseinipourM, et al. (2007) Tuberculosis after initiation of antiretroviral therapy in low-income and high-income countries. Clin Infect Dis 45: 1518–1521.

58. LawnSD, WilkinsonRJ, LipmanMC, WoodR (2008) Immune reconstitution and “unmasking” of tuberculosis during antiretroviral therapy. Am J Respir Crit Care Med 177: 680–685.

59. Rothman K, GreenlandS, LashT (2008) Modern epidemiology. Philadelphia: Lippincott Williams & Wilkins.

60. SterneJA, GavaghanD, EggerM (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53: 1119–1129.

61. UyJ, ArmonC, BuchaczK, WoodK, BrooksJT (2009) Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 51: 450–453.

62. World Health Organization (2009) A practical handbook on the pharmacovigilance of antiretroviral medicines. Available: http://www.who.int/hiv/topics/pharmacovigilance/arv_pharmacovigilance_handbook.pdf. Accessed 8 November 2011.

63. JordanMR, BennettDE, WainbergMA, HavlirD, HammerS, et al. (2012) Update on World Health Organization HIV drug resistance prevention and assessment strategy: 2004–2011. Clin Infect Dis 54 (Suppl 4) S245–S249.

64. ZachariahR, BemelmansM, AkessonA, GomaniP, PhiriK, et al. (2011) Reduced tuberculosis case notification associated with scaling up antiretroviral treatment in rural Malawi. Int J Tuberc Lung Dis 15: 933–937.

65. MiddelkoopK, BekkerLG, MyerL, JohnsonLF, KloosM, et al. (2011) Antiretroviral therapy and TB notification rates in a high HIV prevalence South African community. J Acquir Immune Defic Syndr 56: 263–269.

66. DasM, ChuPL, SantosGM, ScheerS, VittinghoffE, et al. (2010) Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS ONE 5: e11068 doi:10.1371/journal.pone.0011068.

67. CowanSA, GerstoftJ, HaffJ, Hartvig ChristiansenA, NielsenJ, et al. (2012) Stable incidence of HIV diagnoses among Danish MSM despite increased engagement in unsafe sex. J Acquir Immune Defic Syndr. E-pub ahead of print doi:10.1097/QAI.0b013e31825af890.

68. MontanerJS, LimaVD, BarriosR, YipB, WoodE, et al. (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.

69. Tanser F, Bärnighausen T, Grapsa E, Newell M-L (2012) Effect of ART coverage on rate of new HIV infections in a hyper-endemic, rural population: South Africa [abstract 136LB]. 19th Conference on Retroviruses and Opportunistic Infections; 5–8 March 2012; Seattle, Washington, United States.

70. Egger M (2011) Community viral load and newly reported HIV infections in Switzerland [IAS satellite session 17 July 2011]. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 17–20 July 2011; Rome, Italy.

71. GranichRM, GilksCF, DyeC, De CockKM, WilliamsBG (2009) Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 373: 48–57.

72. Abdool KarimSS, NaidooK, GroblerA, PadayatchiN, BaxterC, et al. (2010) Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 362: 697–706.

73. BlancFX, SokT, LaureillardD, BorandL, RekacewiczC, et al. (2011) Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 365: 1471–1481.

74. HavlirDV, KendallMA, IveP, KumwendaJ, SwindellsS, et al. (2011) Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 365: 1482–1491.

75. KitahataMM, GangeSJ, AbrahamAG, MerrimanB, SaagMS, et al. (2009) Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 360: 1815–1826.

76. SterneJA, MayM, CostagliolaD, de WolfF, PhillipsAN, et al. (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.

77. The HIV-CAUSAL Collaboration (2011) When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries. Ann Intern Med 154: 509–515.

78. The CASCADE Collaboration (2011) Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med 171: 1560–1569.

79. BärnighausenT, TanserF, DabisF, NewellML (2012) Interventions to improve the performance of HIV health systems for treatment-as-prevention in sub-Saharan Africa: the experimental evidence. Curr Opin HIV AIDS 7: 140–150.

80. World Health Organization (2007) Guidance on provider-initiated HIV testing and counselling in health facilities. Available: http://whqlibdoc.who.int/publications/2007/9789241595568_eng.pdf. Accessed 7 February 2011.

81. World Health Organization (2010) Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Available: http://whqlibdoc.who.int/publications/2010/9789241500395_eng.pdf. Accessed 11 April 2011.

82. Mugglin C, Althoff K, Wools-Kaloustian K, Sterne J, Nash D, et al. (2012) Immunodeficiency at the start of ART: global view [abstract 100]. 19th Conference on Retroviruses and Opportunistic Infections; 5–8 March 2012; Seattle, Washington, United States.

83. SweatM, MorinS, CelentanoD, MulawaM, SinghB, et al. (2011) Community-based intervention to increase HIV testing and case detection in people aged 16–32 years in Tanzania, Zimbabwe, and Thailand (NIMH Project Accept, HPTN 043): a randomised study. Lancet Infect Dis 11: 525–532.

84. LugadaE, MillarD, HaskewJ, GrabowskyM, GargN, et al. (2010) Rapid implementation of an integrated large-scale HIV counseling and testing, malaria, and diarrhea prevention campaign in rural Kenya. PLoS ONE 5: e12435 doi:10.1371/journal.pone.0012435.

85. SutharAB, KlinkenbergE, RamsayA, GargN, BennettR, et al. (2012) Community-based multi-disease prevention campaigns for controlling HIV-associated tuberculosis. Int J Tuberc Lung Dis 16: 430–436.

86. GetahunH, KittikraisakW, HeiligCM, CorbettEL, AylesH, et al. (2011) Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med 8: e1000391 doi:10.1371/journal.pmed.1000391.

87. AkoloC, AdetifaI, ShepperdS, VolminkJ (2010) Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev 2010: CD000171.

88. Tuberculosis preventive therapy in HIV-infected individuals: a joint statement of the WHO Tuberculosis Programme and the Global Programme on AIDS, and the International Union Against Tuberculosis and Lung Disease (IUATLD). Wkly Epidemiol Rec 68: 361–364.

89. World Health Organization, Joint United Nations Programme on HIV/AIDS (1998) Policy statement on preventive therapy against tuberculosis. Available: http://whqlibdoc.who.int/hq/1998/WHO_TB_98.255.pdf. Accessed 30 June 2010.

90. CharalambousS, GrantAD, InnesC, HoffmannCJ, DowdeswellR, et al. (2010) Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme. AIDS 24 (Suppl 5) S5–S13.

91. FennerL, ForsterM, BoulleA, PhiriS, BraitsteinP, et al. (2011) Tuberculosis in HIV programmes in lower-income countries: practices and risk factors. Int J Tuberc Lung Dis 15: 620–627.

92. Durovni B, Saraceni V, Pacheco A, Cavalcante S, Cohn S, et al. (2011) Impact of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) on incidence of TB and death in the TB/HIV in Rio de Janeiro (THRio) study [abstract WELBB02]. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 17–20 July 2011; Rome, Italy.

93. GranichR, GuptaS, SutharAB, SmythC, HoosD, et al. (2011) Antiretroviral therapy in prevention of HIV and TB: update on current research efforts. Curr HIV Res 9: 446–469.

94. AnglemyerA, RutherfordGW, EggerM, SiegfriedN (2011) Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. Cochrane Database Syst Rev 2011: CD009153.

95. PodlekarevaD, MocroftA, DragstedUB, LedergerberB, BeniowskiM, et al. (2006) Factors associated with the development of opportunistic infections in HIV-1-infected adults with high CD4+ cell counts: a EuroSIDA study. J Infect Dis 194: 633–641.

96. The HIV-CAUSAL Collaboration (2012) Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries. Clin Infect Dis 54: 1364–1372.

97. AIDS Clinical Trials Group (2007) Appendix 60: diagnoses appendix. Available: http://www.hptn.org/web%20documents/HPTN052/Appendix60V1.123Feb2007.pdf. Accessed 23 August 2011.

98. American Thoracic Society (1990) Diagnostic standards and classification of tuberculosis. Am Rev Respir Dis 142: 725–735.