Zachariah R, Fitzgerald M, Massaquoi M, Pasulani O, Arnould L, Makombe S, Harries AD. Risk Factors for High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi. AIDS. 2006 Nov 28;20(18):2355-60.
To determine the cumulative proportion of deaths that occur within three and six months of starting ART, and to identify risk factors associated with early mortality among adults initiating ART in a rural district hospital.
This was an observational cohort study.
The study took place in a main district hospital in Thyolo district, Malawi, from April 2003 to April 2005.
All adults who were ART-naive and starting treatment in the main district hospital over the two-year study period were enrolled.
There was no intervention in this study.
The primary outcome was mortality at three months and six months after initiation of ART.
Complete data were available for 1507 participants (34% male), and the median age was 35 years. At ART initiation, 76% were in WHO stage III, 23% in stage IV, and 1% in WHO stage II but with CD4 count ≤ 200 cells/µL. Fifteen percent had active TB, and all of these were also receiving TB treatment. All enrollees were also taking cotrimoxazole prophylaxis. The median CD4 count was 123 cells/µL, the mean BMI was 19.6 kg/m2, and 36% of those starting ART were malnourished. With 1361 person-years of follow-up, 78% were alive and on ART at the end of the study, 2.5% transferred out, 3% were lost to follow-up, and 3.5% had stopped ART. There were 190 (12.6%) deaths. Of the 190 deaths, 61% occurred in the first three months and 79% within six months. Significant risk factors associated with mortality in the first three months after adjustment were WHO stage IV disease (OR 2.1, CI: 1.4-3.3), CD4 count below 50 cells/µL (OR: 2.2, CI: 1.2-4.0), and increasing grades of malnutrition based on BMI (OR for BMI less than 16.0 kg/m2: 6.0(4.6-12.7). Similar results were found for deaths within six months. The trend of increasing mortality with increasing malnutrition and decreasing CD4 counts for the three-month and six-month follow-up time was significant (p<0.001 for both). Among those who died in the first week, 91% had an active WHO-defined opportunistic infection attributed as the main cause of death, oral recurrent Candida being the most common cause. Sixty-eight percent of those who died in the first three months were malnourished (BMI less than 18.4 kg/m2).
The authors conclude that in a rural district in Malawi, BMI and clinical staging could be important screening tools to identify individuals who, despite initiation of ART, are still at high risk for early mortality.
Using the Newcastle-Ottawa scoring system to evaluate the quality of this observational study, the selection of cases, ascertainment of exposure and loss to follow-up were all adequate, and overall the study was of good methodological quality. Limitations that the authors note include the inability to always determine the exact cause of death, and the lack of viral load testing to assess response to ART.
Studies in Malawi and other developing countries have found that 10 to 15% of those on ART die within a median follow-up period of 15 months.(1,2,3) However, factors associated with this early mortality have not been well studied.
While it has not been shown that interventions targeting malnutrition decrease early mortality among those initiating ART, identification and monitoring of patients starting ART with malnutrition may be helpful in avoiding early mortality.
- Harries AD, Schouten EJ, Libamba E. Scaling up antiretroviral treatment in resource poor settings. Lancet 2006 Jun 3;367(9525):1870-2. (No abstract available.)
- Braitstein P, Brinkhof MW, Dabis F; Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration; ART Cohort Collaboration (ART-CC) groups. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006 Mar 11;367(9513):817-24.
- Coetzee D, Hildebrand K, Boulle A, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 2004 Apr 9;18(6):887-95