Background The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. Methods and Findings We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-na?ve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24. Conclusions Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
References
[1]
Egger M, Hirschel B, Francioli P, Sudre P, Wirz M, et al. (1997) Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study. BMJ 315: 1194–1199.
[2]
World Health Organization (2006) Antiretroviral therapy for HIV Infection in adults and adolescents in resource-limited settings: towards universal access. Recommendations for a public health approach. Geneva: WHO. Available at: http://www.who.int/hiv/pub/guidelines/WH?O%20Adult%20ART%20Guidelines.pdf. Accessed 5 June 2008.
[3]
Gilks CF, Crowley S, Ekpini R, Gove S, Perriens J, et al. (2006) The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 368: 505–510.
[4]
Beck EJ, Vitoria M, Mandalia S, Crowley S, Gilks CF, et al. (2006) National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines. AIDS 20: 1497–1502.
[5]
World Health Organisation, UNAIDS, UNICEF (2007) Towards universal access: scaling up priority HIV/AIDS interventions in the health sector: progress Report, April 2007. Geneva: WHO. Available at: http://libdoc.who.int/publications/2007/?9789241595391_eng.pdf. Accessed 5 June 2008.
[6]
[No authors listed] (2004) National Antiretroviral Treatment Guidelines. Pretoria: National Department of Health. pp. 1–93.
[7]
World Health Organization (1990) Interim proposal for a WHO staging system for HIV infection and disease. Wkly Epidemiol Rec 65: 221–224.
[8]
Coetzee D, Hildebrand K, Boulle A, Maartens G, Louis F, et al. (2004) Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 18: 887–895.
[9]
Bekker LG, Myer L, Orrell C, Lawn S, Wood R (2006) Rapid scale-up of a community-based HIV treatment service: programme performance over 3 consecutive years in Guguletu, South Africa. S Afr Med J 96: 315–320.
[10]
Gebhardt M, Rickenbach M, Egger M (1998) Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study. AIDS 12: 1195–1201.
[11]
Centers for Disease Control (1992) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 41: 1–19.
[12]
Ledergerber B, von Overbeck J, Egger M, Luthy R (1994) The Swiss HIV Cohort Study: rationale, organization and selected baseline characteristics. Soz Praventivmed 39: 387–394.
[13]
Sudre P, Rickenbach M, Taffe P, Janin P, Volkart AC, et al. (2000) Clinical epidemiology and research on HIV infection in Switzerland: the Swiss HIV Cohort Study 1988–2000. Schweiz Med Wochenschr 130: 1493–1500.
[14]
Braitstein P, Brinkhof MWG, Dabis F, Schechter M, Boulle A, 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.
[15]
Mathers CD, Lopez AD, Murray CJL (2006) The burden of disease and mortality by condition: data, methods and results for 2001. Global burden of disease and risk factors. In: Lopez AD, Mathers CD, Ezzati M, Murray CJL, Jamison DT, editors. New York: Oxford University Press. pp. 45–240.
[16]
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367: 1747–1757.
[17]
Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18: 695–706.
[18]
Coviello V, Boggess M (2004) Cumulative incidence estimation in the presence of competing risks. Stata J 4: 103–112.
[19]
Lunn M, McNeil D (1995) Applying Cox regression to competing risks. Biometrics 51: 524–532.
[20]
Badri M, Maartens G, Mandalia S, Bekker LG, Penrod JR, et al. (2006) Cost-effectiveness of highly active antiretroviral therapy in South Africa. PLoS Med 3: e4. doi:10.1371/journal.pmed.0030004.
[21]
Cleary SM, McIntyre D, Boulle AM (2006) The cost-effectiveness of antiretroviral treatment in Khayelitsha, South Africa—A primary data analysis. Cost Eff Resour Alloc 4: 20.
[22]
Sendi PP, Bucher HC, Harr T, Craig BA, Schwietert M, et al. (1999) Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. Swiss HIV Cohort Study. AIDS 13: 1115–1122.
[23]
Harries AD, Nyangulu DS, Hargreaves NJ, Kaluwa O, Salaniponi FM (2001) Preventing antiretroviral anarchy in sub-Saharan Africa. Lancet 358: 410–414.
[24]
Adje C, Cheingsong R, Roels TH, Maurice C, Djomand G, et al. (2001) High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Cote d'Ivoire. J Acquir Immune Defic Syndr 26: 501–506.
[25]
Vergne L, Malonga-Mouellet G, Mistoul I, Mavoungou R, Mansaray H, et al. (2002) Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries. J Acquir Immune Defic Syndr 29: 165–168.
[26]
Orrell C, Bangsberg DR, Badri M, Wood R (2003) Adherence is not a barrier to successful antiretroviral therapy in South Africa. AIDS 17: 1369–1375.
[27]
Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, et al. (2004) Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. J Acquir Immune Defic Syndr 36: 1100–1102.
[28]
Weidle PJ, Wamai N, Solberg P, Liechty C, Sendagala S, et al. (2006) Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda. Lancet 368: 1587–1594.
[29]
Booth CL, Geretti AM (2007) Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection. J Antimicrob Chemother 59: 1047–1056.
[30]
Bessong PO, Mphahlele J, Choge IA, Obi LC, Morris L, et al. (2006) Resistance mutational analysis of HIV type 1 subtype C among rural South African drug-naive patients prior to large-scale availability of antiretrovirals. AIDS Res Hum Retroviruses 22: 1306–1312.
[31]
McConnell MS, Stringer JS, Kourtis AP, Weidle PJ, Eshleman SH (2007) Use of single-dose nevirapine for the prevention of mother-to-child transmission of HIV-1: does development of resistance matter. Am J Obstet Gynecol 197: S56–63.
[32]
Boulle A, Orrel C, Kaplan R, Van Cutsem G, McNally M, et al. (2007) Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort. Antivir Ther 12: 753–760.
[33]
Lawn SD, Bekker LG, Myer L, Orrell C, Wood R (2005) Cryptococcocal immune reconstitution disease: a major cause of early mortality in a South African antiretroviral programme. AIDS 19: 2050–2052.
[34]
Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, et al. (2007) Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health 12: 929–935.
[35]
Centre for the AIDS Programme of Research in South Africa (CAPRISA) (2006) A Study to Compare Three Existing Starting Points of ART Initiation in HIV/TB Co-Infected Patients (SAPIT). Available at: http://clinicaltrials.gov/ct2/show/NCT00?398996. Accessed 10 April 2008.
[36]
University of Cape Town and Médecins Sans Frontières (2007) Isoniazid plus HAART to Prevent TB in HIV-Infected Persons. Available at: http://clinicaltrials.gov/ct2/show/NCT00?463086. Accessed 19 April 2008.
[37]
World Health Organization (2002) Scaling up antiretroviral therapy in resource-limited settings: guidelines for a public health approach. Geneva: WHO.
[38]
World Health Organization (2004) Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach. 2003 Revision. Geneva: WHO. Available at: http://www.who.int/hiv/pub/prev_care/en/?arvrevision2003en.pdf. Accessed 5 June 2008.
[39]
Lawn SD, Myer L, Harling G, Orrell C, Bekker LG, et al. (2006) Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation. Clin Infect Dis 43: 770–776.
[40]
Lawn SD, Myer L, Orrell C, Bekker LG, Wood R (2005) Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 19: 2141–2148.
[41]
Badri M, Lawn SD, Wood R (2006) Short-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: a longitudinal study. Lancet 368: 1254–1259.
[42]
Wolbers M, Bucher H, Furrer H, Rickenbach M, Cavassini M, et al. (2008) Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study (SHCS). Abstract 806. Available at: http://www.retroconference.org/AbstractS?earch/Default.aspx?Conf=17. Accessed 5 June 2008.