Ferradini L, Laureillard D, Prak N, Ngeth C, Fernandez M, Pinoges L et al. Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia. AIDS 2007 Nov 12;21(17):2293-301.
To assess clinical, adherence and virological status of adult patients 24 months after HAART initiation in a resource poor setting.
Retrospective cohort study of adult patients who initiated HAART 24 months (±2 months) prior to the date of data abstraction.
Khmero-Sovietic Hospital, Phnom Penh, Cambodia.
Male and female adult (≥18 years) patients who initiated HAART at the Khmero-Sovietic Friendship Hospital 24 months (±2 months) prior to the date of data abstraction (between 13 December 2004 and 31 March 2005). Among the 2048 HIV-infected patients who initiated HAART through 31 March 2005, 416 adults had started 24±2 months prior to data abstraction and were included in the analysis.
Since 2001 through a Ministry of Health/Médicins Sans Frontières program in Phnom Penh, HAART has been offered free of charge to patients either at World Health Organization (WHO) stage IV irrespective of CD4 cell count, or at any WHO stage with CD4 cell counts ≤200 cells/µl . HAART initiation began with three pre-HAART counseling visits. The initial first-line regimen consisted of stavudine, lamivudine and efavirenz. Patients with intolerance to this combination were offered other alternative first-line regimens. In the case of treatment failure a second-line PI-based treatment was available. Follow-up visits were performed monthly for the first 6 months and bimonthly thereafter with CD4 counts at 6-mo intervals and adherence support counseling at each visit.
Primary outcomes were survival, continuation of HAART, CD4 count, plasma ART concentration, and HIV viral load at 24 months.
Of the 416 adult patients included in the analysis, 59.2% were male and the median age was 33.6 years. At baseline, 95.2% were ART-naive, 48.9% were at WHO stage IV and 41.6% had a body mass index (BMI) less than 18kg/m2. At baseline, the median CD4 cell count was 11 cells/µl. At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Two-thirds of the deaths (35/53, 66%) occurred within the first 6 months after HAART initiation. Among patients with available CD4 cell counts at baseline (N=416), the median CD4 cell gain was +101 cells/ µl (IQR 62-137) at 6 months (n=344), +154 cells/µl (IQR 95-217) at 12 months (n=337) and +233 cells/µl (IQR 156-332) at 24 months (n=346). Of the 346 patients tested at 24 months, 306 (88.4%) had viral loads less than 400 copies/ml. Factors associated with virologic failure at 24 months (viral load greater than 1000 copies/ml) include previous ART exposure (p=0.004), age greater than 35 years (p=0.008) a CD4 cell count <200 cells/µl (p=0.001) or between 200 and 350 cells/µl (p=0.041), an opportunistic infection between 9 and 24 months (p=0.041) or a low plasma antiretroviral concentration at 24 months (p<0.001). Using WHO criteria for switching regimens (CD4 loss >30% between 12 and 24 months) had only a 26% sensitivity and a 54% positive predictive value for a viral load >1000 copies/ml at 24 months.
These positive results after 2 years of initiating HAART in patients with advanced HIV disease are similar or even better than reported and western cohorts and further demonstrate the efficacy of HAART in the medium term in resource-limited settings. Switching HAART regimens solely on the basis of CD4 loss misses the majority of those whose viral load will exceed 1000 copies/ml at 24 months and incorrectly switches half of those with CD4 loss >30%.
This cohort study was of good quality. Inclusion and exclusion criteria were clearly defined, and sufficient time was allowed for events to occur. Losses to follow-up were relatively low, but their possible effect on some results was not acknowledged. For example, the increase in CD4 count at 24 months was undoubtedly due in part to deaths among patients with the most severe disease at baseline. A limitation of this study is that as the results from only one site may not be generalizable even to all ART patients in Cambodia nor to other ART sites in resource poor settings as the standard of care at this site may differ from other ART sites in Cambodia and elsewhere.
African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-limited settings. The favorable outcomes observed in this study are similar or better than those reported in western cohorts.(1,2) The survival rate observed in this study (84.1%) is similar to that reported from a two-year ART outcomes study in South Africa (which found a two year survival rate of 86.3%).(3) The findings of this study are also consistent with other studies conducted in similar settings in that most of the deaths occurred during the first 6 months after HAART initiation.(3,4,5,6,7,8,9) Interestingly, this study included more men (59%) than women, contrary to the preponderance of women in most other ART outcome studies.(3,4) A model to monitor the virological efficacy of HAART mainly based on patients' clinical history has been proposed by Colebunders(10) but needs to be validated.
In resource-limited settings where access to viral load testing is limited, there is a need to better identify groups of patients at risk of treatment failure. The criteria for suspecting treatment failure may vary greatly according to the duration of follow-up and studies analyzing criteria for treatment failure at different time points are needed.
- Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS 2001 Jul 27;15(11):1369-77.
- Bartlett JA, Buda JJ, von Scheele B, Mauskopf JA, Davis EA, Elston R et al. Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview. JAIDS 2006 Mar;41(3):323-31.
- Coetzee D, Hildebrand K, Boulle A, Maartens G, Louis F, Labatala V, Reuter H et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 2004 Apr 9;18(6):887-95.
- Hawkins C, Achenbach C, Fryda W, Ngare D, Murphy R. Antiretroviral durability and tolerability in HIV-infected adults living in urban Kenya. JAIDS 2007 Jul 1; 45(3):304-10.
- Dabis F, Balestre E, Braitstein P, Miotti P, Brinkhof WG, Schneider M et al. Cohort profile: antiretroviral therapy in lower income countries (ART-LINC): international collaboration of treatment cohorts. Int J Epidemiol 2005 Oct;34(5):979-86.
- Ferrandini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L et al. Scaling up of highly active antiretroviral therapy in a rural direct of Malawi: an effectiveness assessment. Lancet 2006 Apr 22;367(9519):1335-42.
- Ivers LC, Kendrick D, Doucette K. Efficacy of antiretroviral therapy programs in resource-poor settings: a meta-analysis of the published literature. Clin Infect Dis 2005 Jul 15;41(2):217-24.
- Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G et al. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med 2005 Dec 1;353(22):2325-34.
- Lawn SD, Myer L, Orrell C, Bekker LG, Wood R. Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 2005 Dec 2;19(18):2141-8.
- Colebunders R, Moses KR, Laurence J, Shihab HM, Semitala F, Lutwama F et al. A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries. Lancet Infect Dis 2006 Jan;6(1):53-9.