Srikantiah, P, Ghidinelli M, Bachani D, Chasombat S, Daoni E, Mustikawati DE, Nhan do T, Pathak LR, San KO, Vun MC, Zhang F, Lo YR, Narain JP. Scale up of national antiretroviral therapy programs: progress and challenges in the Asia pacific region. AIDS. 2010, Sep 24(suppl 3):S62-71.
To review the progress of antiretroviral therapy (ART) service scale-up, program practices and clinical outcomes in low and middle-income countries in Asia.
Nine countries which bear 95% of the HIV burden in the Asia Pacific region: Cambodia, China, India, Indonesia, Myanmar, Nepal, Papua New Guinea (PNG), Thailand and Vietnam.
Secondary data analysis.
Adult and pediatric HIV-infected persons receiving ART.
Antiretroviral therapy (ART) coverage, mortality and loss to follow-up.
Data for analysis were derived from several sources. For antiretroviral scale up and treatment outcomes, data submitted for 2009 and 2010 to the World Health Organization (WHO) Universal Access Report with national data on 49 standardized indicators are reported.(1) In addition, published and unpublished standardized HIV treatment related data submitted to the WHO/UNAIDS/UNICEF Joint Framework were evaluated(2, 3) as well as recent national estimates of the number of HIV-infected persons in each country. Estimates of number of HIV-infected persons eligible for ART were obtained from the 2008 WHO/UNAIDS Report.(4) Additional country-level treatment outcome and scale-up information was obtained though literature and conference proceeding searches.
From 2003 to end 2009 in the nine focus countries, the number of HIV infected persons receiving ART increased from 67,000 to 700,000 persons, or one-third coverage of the estimated 1.5 million persons eligible for treatment. Coverage varied widely by country, from approximately 80% (Cambodia, PNG, Thailand) to 16% (Nepal). These rates were based on assuming a CD4 cell count threshold of 200 cells/µl; coverage rates will decrease if updated recommendations for ART initiation (350 CD4 cells/µl) are used. The distribution of ART provision across the type of service also varied by country. For example, in Vietnam and Indonesia, ART was available at approximately 30% of facilities where other HIV services were provided, whereas in Thailand, ART is available at 95% of more than 1,000 designated public health hospitals. Expansion of ART services for children has been slower, largely because of limited availability of pediatric drug formulations, and the need for focused efforts to diagnose and refer eligible children.
National Treatment Guidelines were in place for all nine countries; three countries (PNG, Thailand, Cambodia) had updated guidelines recommending initiation of ART at CD4 cell count ≥350 cells/µl regardless of clinical stage, with revision of guidelines being considered or planned in other countries. In all countries, with the exception of Thailand which is planning a pilot program of ART for all pregnant women, criteria for ART initiation for pregnant women is the same as for those who are not pregnant.
First line ART regimens are for two nucleoside reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), with eight out of nine countries recommending zidovudine (AZT) plus lamivudine (3TC) as the preferred NRTI backbone, eliminating stavudine (D4T) due to its potential for toxicity. Only in Thailand, is tenofovir (TDF) included as a preferred first-line NRTI. Only China and Thailand recommend routine HIV ribonucleic acid (RNA) testing. Clinical outcome data are available from some but not all countries. These data indicate that 65-88% of patients remain alive and on treatment at one year, and 71-78% are alive and on treatment at 24 months. Data from Thailand and India show an 11% mortality rate in the first 12 months of ART, with the majority of deaths (including data from China) occurring in the first six months and among those with baseline CD4<50 cells/µl. The median CD4 cell count at which patients initiate ART remained low, from 41-119 cells/µl. Loss to follow up (LFU) ranged from 8.8% at 1.6 years to 16% at two years. Changes and substitutions in first-line ART regimens were needed in almost 20% of patients (Indian and Thai data), mostly due to medication-related adverse events. Data on pediatric outcomes were limited, although survival was 93% at 12 months, 89% at 30 months and 88% at five years, but this was based on only a few studies and a small number of children. Data were not available on the proportion of patients requiring a switch to second line regimens, although a few countries are using viral load testing to diagnose and manage treatment failures. The proportion of persons co-infected with TB and HIV who were on treatment for both was low, only 3-27%. Isoniazid (INH) prophylaxis is not in place, except for pilot programs in two countries.
There has been a significant scale-up of services and ART coverage in this region during the last five years. Most countries, receive substantial support for these programs from external donor funding, except Thailand and China which provide primarily governmental support. Short term survival is comparable to reported outcomes from other resource-limited settings.5,6 Treatment of those with HIV-TB co-infections remains poor. Data on the need for second-line therapy and how to identify it will need to be scaled up.
This was a good quality study. Out of necessity, data were limited primarily to that derived from public sector programs. In some countries, the private sector plays a significant role in providing treatment.
Programs face several key challenges, including successful referral of HIV infected patients to ART at an earlier stage of disease. Data from this region show that patients continue to start ART at low CD4 counts which increases early mortality and leads to overall poorer outcomes.7 Relying solely on clinical or immunological criteria to diagnose treatment failure may result in HIV drug resistance mutations; data on failure and resistance need to be collected. Because of the significant external funding support for rapid scale up, long term sustainability of free ART will depend on national level financial commitment to ART programs. It will also be important to collect data on longer term outcomes, as LFU and treatment failure become more significant.
- World Health Organization. Toward Universal Access: Scaling up Priority Interventions in the Health Sector, 2009 Progress Report. Geneva; 2009.
- WHO UNICEF UNAIDS. Joint reporting tool on the health sector response to HIV/AIDS 2009. Geneva, Switzerland; 2009 [cited July 2009].
- WHO/UNICEF/UNAIDS. Joint reporting tool on the health sector response to HIV/AIDS 2010. Geneva, Switzerland; 2010 [cited 19 July 2010].
- World Health Organization. Toward universal access: scaling up priority HIV/AIDS interventions in the health sector. Geneva; 2008.
- Ferradini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L, et al. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet 2006; 367:1335-1342.
- Stringer JS, Zulu I, Levy J, Stringer EM, Mwango A, Chi BH, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006;296:782- 793.
- Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 2008; 22:1897-1908.