Lowrance DW, Makombe S, Harries AD, et al. A public health approach to rapid scale-up of antiretroviral treatment in Malawi during 2004-2006. J Acquir Immune Defic Syndr. 2008 Nov; 49(3):287-93.
To determine whether the public health approach to rapid scale-up of antiretroviral treatment (ART) has been successful in Malawi
Analysis of aggregated national quarterly and longitudinal cohort data from ART clinics in Malawi from October 2004 to December 2006
Public-sector ART clinic sites in Malawi
Among adults and children registered for ART at public clinics by December 31, 2006 (n=81,821), 70% were known to be on ART, 9% had transferred to another site, 11% had died, 9% were lost to follow-up, and 1% stopped treatment. Since national standardized and routine ART data collection began October 1, 2004, 72,666 patients had been newly registered and were included in the cohort analysis. Patients newly initiated on ART during the quarter are followed over time, and survival outcomes are assessed at 6 and 12 months. For this analysis, nine quarters of patient data were included: fourth quarter 2004 through fourth quarter 2006.
The national public health approach to ART scale-up beginning in October 2004 in Malawi is based on simplified clinical decision making, standardized ART regimens, non-physician care, limited laboratory support, and centralized monitoring and evaluation. By December 31, 2007, this approach resulted in 141,000 persons being initiated on ART in the public sector. The National Monitoring and Evaluation System implemented standardized monitoring tools used at each clinic, including a patient register and a patient master card. Patient information incorporated in these tools includes a unique ART registration number, age, sex, occupation, HIV test date and place, reason for starting ART, key opportunistic infections, and the drug regimen. During follow-up each month, information is recorded on the patient master cards, such as alive on ART, dead, default (lost to follow-up for more than 90 days), transferred out, or stopped treatment. Based on recorded data, cumulative and quarterly cohort reports are generated. Patients who initiated ART before October 1, 2004 were retrospectively included in the cumulative and initial 12-month longitudinal cohorts. In July 2006, the Ministry of Health began quarterly assessments of data quality; ART clinics are given certificates of excellence for high performance.
Primary outcomes included access to treatment and key early clinical outcomes, such as mortality, program retention, and 6- and 12-month survival probability.
To measure access to treatment, linear trends in aggregate facility-level quarterly cohort data, including baseline patient demographic and clinical characteristics and end-of-quarter outcomes were analyzed using mixed-effects logistic regression models with random effects on the intercept to account for clustering of patients within facilities. The same was used for nonlinear trends in 6- and 12-month longitudinal cohort survival data. Survival probabilities were calculated using the actuarial method to give the number alive at the end of the interval.
By December 31, 2006, 104 public sector ART sites had been established in Malawi, up from 23 sites in October 2004. In terms of access to treatment, 60%-63% of patients initiating ART during the nine study quarters were women. There were significant increases in trends of children and subsistence farmers initiating ART: 5.5% to 9.0% (P<0.0001 for trend), and from 23% to 32% (P<0.0001 for trend), respectively. The trend in the percentage of patients who initiated ART with WHO stage I and II with CD4 cell count <250 cells/mL increased (P<0.001 for trend) while those initiating ART with WHO clinical stage IV decreased from 26% to 21% during this period (P<0.001 for trend).
In terms of early clinical outcomes across quarters, the percentage known to have died was between 3% and 5% and the percentage of patients known to be alive on ART was between 93% and 96%. Patients who transferred out increased from <1% to 2% (P<0.001 for trend). Ninety-nine percent of patients alive at the end of the quarter remained on the first-line regimen. Percentage of patients reported to be working was between 89% and 94%, while 96% to 99% of patients were reported as ambulatory (P<0.001 for trend). Among the 65% of patients that had their pill counts assessed, patient adherence ≥95% was between 93% and 97%.
In terms of survival probability, 6-month survival probability decreased from 87% in quarter 1 to 85% in quarter 4, then increased to 88% in quarter 7 (P<0.05 linear; P<0.01 quadratic). Twelve-month survival probability decreased from 84% in quarter 1 to 81% in quarter 5 and increased to 82% in quarter 7 (P<0.01 linear; P<0.01 quadratic).
Using multivariate analysis, facility characteristics were analyzed to examine associations in survival probabilities. Location in the southern region, low patient enrollment, and being a government site were statistically significant characteristics at the facility level associated with lower 6-month survival probability. Low numbers of ART patients enrolled and being a government clinic were statistically significant associations with lower 12-month survival probabilities.
The authors conclude that during the first 27 months of scale-up, Malawi maintained or improved the quality of national ART services.
Using the Newcastle-Ottawa grading system for cohort studies, this study received a high rating. The selection of cohort was based on the standardized nationalized monitoring and evaluation system, baseline measurements were assessed, and the measurement of outcome variables were adequately analyzed and properly presented in the text and tables. The authors noted several limitations to the analyses, including no patient level, which restricted the type of analysis; some ART facilities had missing data, especially in the early stages of the scale-up; and the numbers of patients in quarterly cohorts included double-counting transfers, which the authors estimated at 10% of total registered, which, the authors point out, may have led to an incorrect estimation of survival probability.
The Malawi example provides evidence, in the face of a growing number of untreated HIV-infected individuals in sub-Saharan Africa, that the adapted WHO-recommended public health approach to rapid ART scale-up is possible and successful.(1,2) Medication adherence was better than expected, and national ART patient survival estimates and retention compare favorably with data in other resource-limited settings.(3) Of note, however, is the increased demand for services that comes with scale-up; many of the clinics in Malawi are at capacity, and the demand for reliable monitoring and evaluation often can be overwhelming for clinics.(4,5,6) Thus, further expansion may require innovative data collection tools and allocation of responsibilities.
Malawi's successful public health approach to rapid ART scale-up can serve as a model for other resource-limited settings that need to make a difficult choice: 1) provide slower but more robust resource-intensive service delivery, or 2) provide a more rapid model with minimal support services that will provide greater access and increase survival in a shorter period of time.
- Gilks CF, Crowley S, Ekpini R, et al. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 2006;368:505-10.
- Harries AD, Schouten EJ, Makombe SD, et al. Ensuring uninterrupted supplies of antiretroviral drugs in resource-poor settings: an example from Malawi. Bull World Health Organ 2007;85:152-5.
- Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med 2007;4(10):e298. doi:10.1371/journal.pmed.0040298.
- Lowrance D, Filler S, Makombe S, et al. Assessment of a national monitoring and evaluation for rapid expansion of antiretroviral treatment in Malawi. Trop Med Int Health. 2007;12:377-81.
- Makombe SD, Hochgesang M, Jahn A, et al. Assessing the quality of data aggregated by antiretroviral treatment clinics in Malawi. Bull World Health Organ 2008;86:310-4.
- Boerma JT, Stanecki KA, Newell M-L, et al. Monitoring of scale-up of antiretroviral therapy programmes: methods to estimate coverage. Bull World Health Organ 2006;84:145-50.