HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa
Background:
Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.
Methods and Findings:
Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results.
Conclusions:
Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.
: Please see later in the article for the Editors' Summary
Vyšlo v časopise:
HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa. PLoS Med 9(7): e32767. doi:10.1371/journal.pmed.1001245
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001245
Souhrn
Background:
Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.
Methods and Findings:
Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results.
Conclusions:
Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.
: Please see later in the article for the Editors' Summary
Zdroje
1. MontanerJSGHoggRWoodEKerrTTyndallM 2006 The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet 368 531 536 doi:10.1016/S0140-6736(06)69162-9
2. De CockKMGilksCFLoY-RGuermaT 2009 Can antiretroviral therapy eliminate HIV transmission? Lancet 373 7 9 doi:10.1016/S0140-6736(08)61732-8
3. GarnettGPBaggaleyRF 2009 Treating our way out of the HIV pandemic: could we, would we, should we? Lancet 373 9 11 doi:10.1016/S0140-6736(08)61698-0
4. CohenJ 2011 Halting HIV/AIDS epidemics. Science 334 1338 1340
5. GranichRGuptaSSutharASmythCHoosD 2011 Antiretroviral therapy in prevention of HIV and TB: update on current research efforts. Curr HIV Res 9 446 469 doi:10.2174/157016211798038597
6. QuinnTCWawerMJSewankamboNSerwaddaDLiC 2000 Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 342 921 929 doi:10.1056/NEJM200003303421303
7. FraserCHollingsworthTDChapmanRde WolfFHanageWP 2007 Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci U S A 104 17441 17446 doi:10.1073/pnas.0708559104
8. VernazzaPLTroianiLFleppMJConeRWSchockJ 2000 Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study. AIDS 14 117 121
9. Cu-UvinSCaliendoAMReinertSChangAJuliano-RemollinoC 2000 Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS 14 415 421
10. BaggaleyRFFergusonNMGarnettGP 2005 The epidemiological impact of antiretroviral use predicted by mathematical models: a review. Emerg Themes Epidemiol 2 9 doi:10.1186/1742-7622-2-9
11. DoddPJGarnettGPHallettTB 2010 Examining the promise of HIV elimination by “test and treat" in hyperendemic settings. AIDS 24 729 735 doi:10.1097/QAD.0b013e32833433fe
12. AndersonRMGuptaSMayRM 1991 Potential of community-wide chemotherapy or immunotherapy to control the spread of HIV-1. Nature 350 356 359 doi:10.1038/350356a0
13. GilliamBLDyerJRFiscusSAMarcusCZhouS 1997 Effects of reverse transcriptase inhibitor therapy on the HIV-1 viral burden in semen. J Acquir Immune Defic Syndr Hum Retrovirol 15 54 60
14. BlowerSMGershengornHBGrantRM 2000 A tale of two futures: HIV and antiretroviral therapy in San Francisco. Science 287 650 654
15. DangerfieldBCFangYRobertsCA 2001 Model-based scenarios for the epidemiology of HIV/AIDS: the consequences of highly active antiretroviral therapy. Syst Dyn Rev 17 119 150 doi:10.1002/sdr.211
16. LawMGPrestageGGrulichAVan de VenPKippaxS 2001 Modelling the effect of combination antiretroviral treatments on HIV incidence. AIDS 15 1287 1294
17. Velasco-HernandezJXGershengornHBBlowerSM 2002 Could widespread use of combination antiretroviral therapy eradicate HIV epidemics? Lancet Infect Dis 2 487 493 doi:10.1016/S1473-3099(02)00346-8
18. XiridouMGeskusRDe WitJCoutinhoRKretzschmarM 2003 The contribution of steady and casual partnerships to the incidence of HIV infection among homosexual men in Amsterdam. AIDS 17 1029 1038 doi:10.1097/01.aids.0000050879.72891.1d
19. GrayRHLiXWawerMJGangeSJSerwaddaD 2003 Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda. AIDS 17 1941 1951 doi:10.1097/01.aids.0000076313.76477.fc
20. BlowerSBodineEKahnJMcFarlandW 2005 The antiretroviral rollout and drug-resistant HIV in Africa: insights from empirical data and theoretical models. AIDS 19 1 14
21. BaggaleyRFGarnettGPFergusonNM 2006 Modelling the impact of antiretroviral use in resource-poor settings. PLoS Med 3 e124 doi:10.1371/journal.pmed.0030124
22. McCormickAWWalenskyRPLipsitchMLosinaEHsuH 2007 The effect of antiretroviral therapy on secondary transmission of HIV among men who have sex with men. Clin Infect Dis 44 1115 1122 doi:10.1086/512816
23. SalomonJAHoganDR 2008 Evaluating the impact of antiretroviral therapy on HIV transmission. AIDS 22 Suppl 1 S149 S159 doi:10.1097/01.aids.0000327636.82542.87
24. AttiaSEggerMMüllerMZwahlenMLowN 2009 Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS 23 1397 1404 doi:10.1097/QAD.0b013e32832b7dca
25. ReynoldsSJMakumbiFNakigoziGKagaayiJGrayRH 2011 HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. AIDS 25 473 477 doi:10.1097/QAD.0b013e3283437c2b
26. DonnellDBaetenJMKiarieJThomasKKStevensW 2010 Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 375 2092 2098 doi:10.1016/S0140-6736(10)60705-2
27. GlynnJRPriceAFloydSMolesworthAKayuniN 2011 Anitretroviral therapy reduces HIV transmission in discordant couples in northern Malawi. Sex Transm Infect 87 A218 doi:10.1136/sextrans-2011-050108.277
28. CohenMSChenYQMcCauleyMGambleTHosseinipourMC 2011 Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365 493 505 doi:10.1056/NEJMoa1105243
29. LodwickRCostagliolaDReissPTortiCTeiraR 2010 Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years. Arch Intern Med 170 410 419 doi:10.1001/archinternmed.2009.472
30. BoulleAVan CutsemGHilderbrandKCraggCAbrahamsM 2010 Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 24 563 572 doi:10.1097/QAD.0b013e328333bfb7
31. NashDKatyalMBrinkhofMWGKeiserOMayM 2008 Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies. AIDS 22 2291 2302 doi:10.1097/QAD.0b013e3283121ca9
32. Joint United Nations Programme on HIV/AIDS 2010 Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Progress report 2010. Available: http://whqlibdoc.who.int/publications/2010/9789241500395_eng.pdf. Accessed 19 December 2011
33. Joint United Nations Programme on HIV/AIDS 2011 World AIDS Day Report 2011. How to get to zero: faster, smarter, better. Available: http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/JC2216_WorldAIDSday_report_2011_en.pdf. Accessed 23 December 2011
34. GranichRMGilksCFDyeCDe CockKMWilliamsBG 2009 Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 373 48 57 doi:10.1016/S0140-6736(08)61697-9
35. WagnerBGBlowerS 2009 Voluntary universal testing and treatment is unlikely to lead to HIV elimination: a modeling analysis. doi:10.1038/npre.2009.3917.1
36. KretzschmarMEvan der LoeffMFCoutinhoRA 2012 Elimination of HIV by test and treat. AIDS 26 247 248 doi:10.1097/QAD.0b013e32834e1592
37. BacaërNPretoriusCAuvertB 2010 An age-structured model for the potential impact of generalized access to antiretrovirals on the South African HIV epidemic. Bull Math Biol 72 2180 2198 doi:10.1007/s11538-010-9535-2
38. BendavidEBrandeauMLWoodROwensDK 2010 Comparative effectiveness of HIV testing and treatment in highly endemic regions. Arch Intern Med 170 1347 1354 doi:10.1001/archinternmed.2010.249
39. World Health Organization 2010 Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach, 2010 revision. Available: http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. Accessed 22 December 2011
40. PEPFAR Scientific Advisory Board 2011 PEPFAR Scientific Advisory Board recommendations for the Office of the US Global AIDS Coordinator: implications of HPTN 052 for PEPFAR's treatment programs. Available: http://www.pepfar.gov/documents/organization/177126.pdf. Accessed 19 December 2011
41. SchwartländerBStoverJHallettTAtunRAvilaC 2011 Towards an improved investment approach for an effective response to HIV/AIDS. Lancet 377 2031 2041 doi:10.1016/S0140-6736(11)60702-2
42. HontelezJAde VlasSJTanserFBakkerRBärnighausenT 2011 The impact of the new WHO antiretroviral treatment guidelines on HIV epidemic dynamics and cost in South Africa. PLoS ONE 6 e21919 doi:10.1371/journal.pone.0021919
43. JohnsonLFHallettTBRehleTMDorringtonRE 2012 The effect of changes in condom usage and antiretroviral treatment coverage on human immunodeficiency virus incidence in South Africa: a model-based analysis. J R Soc Interface 9 1544 1554 doi:10.1098/rsif.2011.0826
44. BoilyMCMâsseBAlsallaqRPadianNSEatonJW 2012 HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention. PLoS Med 9 e1001250 doi:10.1371/journal.pmed.1001250
45. JohnsonLF 2012 Access to antiretroviral treatment in South Africa, 2004–2011. South Afr J HIV Med 13 22 27
46. South Africa National AIDS Council 2011 National strategic plan on HIV, STIs and TB: 2012–2016 summary. Available: http://www.doh.gov.za/docs/stratdocs/2012/NSPsum.pdf. Accessed 25 May 2012
47. ShisanaORehleTSimbayiLCZumaKJoosteS 2009 South African national HIV prevalence, incidence, behaviour and communication survey 2008: a turning tide amongst teenagers? Cape Town HSRC Press
48. Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat 2011 World population prospects: the 2010 revision. Available: http://esa.un.org/unpd/wpp/index.htm. Accessed 19 December 2011
49. The HIV Modelling Consortium Treatment as Prevention Editorial Writing Group 2012 HIV treatment as prevention: models, data, and questions—Towards evidence-based decision-making. PLoS Med 9 e1001259 doi:10.1371/journal.pmed.1001259
50. AndersonRMMayRM 1992 Infectious diseases of humans: dynamics and control Oxford Oxford University Press
51. UNAIDS/WHO/SACEMA Expert Group on Modelling the Impact and Cost of Male Circumcision for HIV Prevention 2009 Male circumcision for HIV prevention in high HIV prevalence settings: what can mathematical modelling contribute to informed decision making? PLoS Med 6 e1000109 doi:10.1371/journal.pmed.1000109
52. HankinsCAGlasserJWChenRT 2011 Modeling the impact of RV144-like vaccines on HIV transmission. Vaccine 29 6069 6071 doi:10.1016/j.vaccine.2011.07.001
53. HalloranMEFergusonNMEubankSLonginiIMCummingsDA 2008 Modeling targeted layered containment of an influenza pandemic in the United States. Proc Natl Acad Sci U S A 105 4639 4644 doi:10.1073/pnas.0706849105
54. AlthausCLTurnerKMSchmidBVHeijneJCKretzschmarM 2011 Transmission of Chlamydia trachomatis through sexual partnerships: a comparison between three individual-based models and empirical data. J R Soc Interface 9 136 146 doi:10.1098/rsif.2011.0131
55. BateganyaMColfaxGShaferLAKityoCMugyenyiP 2005 Antiretroviral therapy and sexual behavior: a comparative study between antiretroviral-naive and -experienced patients at an urban HIV/AIDS care and research center in Kampala, Uganda. AIDS Patient Care STDS 19 760 768
56. 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
57. EiseleTPMathewsCChopraMLurieMNBrownL 2009 Changes in risk behavior among HIV-positive patients during their first year of antiretroviral therapy in Cape Town South Africa. AIDS Behav 13 1097 1105 doi:10.1007/s10461-008-9473-2
58. McClellandRSGrahamSMRichardsonBAPeshuNMaseseLN 2010 Treatment with antiretroviral therapy is not associated with increased sexual risk behavior in Kenyan female sex workers. AIDS 24 891 897 doi:10.1097/QAD.0b013e32833616c7
59. VenkateshKKde BruynGLurieMNMohapiLPronykP 2010 Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics. AIDS 24 2687 2696 doi:10.1097/QAD.0b013e32833e78d4
60. VenkateshKKFlaniganTPMayerKH 2011 Is expanded HIV treatment preventing new infections? Impact of antiretroviral therapy on sexual risk behaviors in the developing world. AIDS 25 1939 1949 doi:10.1097/QAD.0b013e32834b4ced
61. BezemerDde WolfFBoerlijstMCvan SighemAHollingsworthTD 2008 A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy. AIDS 22 1071 1077 doi:10.1097/QAD.0b013e3282fd167c
62. SmithMKPowersKAMuessigKEMillerWCCohenMS 2012 HIV treatment as prevention: the utility and limitations of ecological observation. PLoS Med 9 e1001260 doi:10.1371/journal.pmed.1001260
63. WilsonDP 2012 HIV treatment as prevention: natural experiments highlight limits of antiretroviral treatment as HIV prevention. PLoS Med 9 e1001231 doi:10.1371/journal.pmed.1001231
64. BarthREvan der LoeffMFSchuurmanRHoepelmanAIWensingAM 2010 Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis 10 155 166 doi:10.1016/S1473-3099(09)70328-7
65. VardavasRBlowerS 2007 The emergence of HIV transmitted resistance in Botswana: “when will the WHO detection threshold be exceeded?" PLoS ONE 2 e152 doi:10.1371/journal.pone.0000152
66. PhillipsANPillayDGarnettGBennettDVitoriaM 2011 Effect on transmission of HIV-1 resistance of timing of implementation of viral load monitoring to determine switches from first to second-line antiretroviral regimens in resource-limited settings. AIDS 25 843 850 doi:10.1097/QAD.0b013e328344037a
67. WagnerBGKahnJSBlowerS 2010 Should we try to eliminate HIV epidemics by using a “Test and Treat" strategy? AIDS 24 775 776 doi:10.1097/QAD.0b013e3283366782
68. BoilyM-CBaggaleyRFWangLMasseBWhiteRG 2009 Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 9 118 129 doi:10.1016/S1473-3099(09)70021-0
69. HollingsworthTDAndersonRMFraserC 2008 HIV-1 transmission, by stage of infection. J Infect Dis 198 687 693 doi:10.1086/590501
70. WawerMJGrayRHSewankamboNKSerwaddaDLiX 2005 Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 191 1403 1409 doi:10.1086/429411
71. CohenMSDyeCFraserCMillerWCPowersKA 2012 HIV treatment as prevention: debate and commentary—will early infection compromise treatment-as-prevention strategies? PLoS Med 9 e1001232 doi:10.1371/journal.pmed.1001232
72. PowersKAGhaniACMillerWCHoffmanIFPettiforAE 2011 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 78 256 268 doi:10.1016/S0140-6736(11)60842-8
73. RosenSFoxMP 2011 Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med 8 e1001056 doi:10.1371/journal.pmed.1001056
74. CornellMGrimsrudAFairallLFoxMPvan CutsemG 2010 Temporal changes in programme outcomes among adult patients initiating antiretroviral therapy across South Africa, 2002–2007. AIDS 24 2263 2270 doi:10.1097/QAD.0b013e32833d45c5
75. The US President's Emergency Plan for AIDS Relief 2011 August Guidance for the prevention of sexually transmitted HIV infections. Available: http://www.pepfar.gov/documents/organization/171303.pdf. Accessed 19 March 2012
76. MaherDBiraroSHosegoodVIsingoRLutaloT 2010 Translating global health research aims into action: the example of the ALPHA network. Trop Med Int Health 15 321 328 doi:10.1111/j.1365-3156.2009.02456.x
77. StoverJBollingerLAvilaC 2011 Estimating the impact and cost of the WHO 2010 recommendations for antiretroviral therapy. AIDS Res Treat 2011 738271 doi:10.1155/2011/738271
78. StoverJJohnsonPHallettTMarstonMBecquetR 2010 The Spectrum projection package: improvements in estimating incidence by age and sex, mother-to-child transmission, HIV progression in children and double orphans. Sex Transm Infect 86 Suppl 2 ii16 ii21 doi:10.1136/sti.2010.044222
79. TanserFHosegoodVBärnighausenTHerbstKNyirendaM 2008 Cohort profile: Africa Centre Demographic Information System (ACDIS) and population-based HIV survey. Int J Epidemiol 37 956 962 doi:10.1093/ije/dym211
80. AIDS 2031 Commission 2010 AIDS in an uncertain world: the report of the AIDS 2031 Commission Upper Saddle River (New Jersey) Prentice Hall
81. LongEBrandeauM 2010 The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Ann Intern Med 158 778 789
82. HontelezJALurieMNNewellMLBakkerRTanserF 2011 Ageing with HIV in south africa. AIDS 25 1665 1667 doi:10.1097/QAD.0b013e32834982ea
83. HontelezJANagelkerkeNBärnighausenTBakkerRTanserF 2011 The potential impact of RV144-like vaccines in rural South Africa: a study using the STDSIM microsimulation model. Vaccine 29 6100 6106 doi:10.1016/j.vaccine.2011.06.059
84. JohnsonLDorringtonRBradshawDPillay-Van WykVRehleT 2009 Sexual behaviour patterns in South Africa and their association with the spread of HIV: insights from a mathematical model. Demogr Res 21 289 340 doi:10.4054/DemRes.2009.21.11
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2012 Číslo 7
- Statinová intolerance
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Metamizol v liečbe pooperačnej bolesti u detí do 6 rokov veku
- Co dělat při intoleranci statinů?
Najčítanejšie v tomto čísle
- HIV Treatment as Prevention: Issues in Economic Evaluation
- HIV Treatment as Prevention: The Utility and Limitations of Ecological Observation
- Consequences of Gestational Diabetes in an Urban Hospital in Viet Nam: A Prospective Cohort Study
- HIV Treatment as Prevention: Optimising the Impact of Expanded HIV Treatment Programmes