The Zambian national program for HIV care and treatment was implemented in Lusaka’s public health sector in April 2004 and has expanded rapidly 3, 12
. Briefly, HIV-infected patients are enrolled in care and undergo a history and physical, WHO staging, and a CD4+
lymphocyte count. Weight and height (i.e. the components of BMI) are recorded at the initial visit, and weight is recorded at subsequent visits. Patients with WHO stage 4 disease; a CD4+
lymphocyte count <200 cells/mm3
; or WHO stage 3 disease and a CD4+
lymphocyte count <350 mm3
are eligible to initiate ART. During the study period, the first line regimen was a non-nucleoside reverse transcriptase inhibitor (NNRTI), either efavirenz (EFV) or nevirapine (NVP), in combination with two nucleoside reverse transcriptase inhibitors (NRTIs): lamivudine (3TC) with either zidovudine (ZDV) or stavudine (d4T). In July 2007, tenofovir and emtricitabine (TDF/FTC) was introduced as the first line NRTI combination. Patients on treatment prior to July 2007 remained on the original regimen, except in cases of treatment failure or toxicity.
Toxicity and clinical disease progression are monitored closely after ART initiation through an intensive visit schedule. Once deemed stable by clinicians, patients return for pharmacy visits every one to three months and clinical visits every three months. A CD4+ lymphocyte count is performed every six months or at shorter intervals if there is evidence of disease progression. Determination of treatment failure is based on WHO staging (clinical failure) and/or CD4+ lymphocyte count (immunologic failure) criteria. These include a new or recurrent WHO stage 3 or 4 condition while on ART for greater than six months, a <50 cells/mm3 CD4+ lymphocyte increase after six months of ART, a CD4+ lymphocyte count <100 cells/mm3 after 12 months, a > 30% decline in CD4+ lymphocyte count from the peak post-ART value, or a decline in CD4+ lymphocyte count to value below that of treatment initiation. Plasma HIV RNA measurements, where available, are used sparingly. If adherence is determined to be adequate, patients failing treatment are changed to a second line regimen, typically a protease inhibitor (PI) with concomitant NRTI changes.
Nutrition counseling is provided at enrollment in the ART program, and clinicians have the option to refer patients at any visit for further information on healthy eating habits. Additionally, from 2004 to 2006 a World Food Programme (WFP) pilot study of food supplementation for HIV-infected persons was carried out at 10 clinics 13
. This program provided individual and household rations for six to 12 months, based on an assessment of food insecurity in the home. Eligibility criteria did not include BMI or other anthropometric or biochemical measures.
We analyzed data from a cohort of HIV-infected adults (>15 years of age) who started ART between May 1, 2004 and April 31, 2008. To be included, patients were required to have a baseline BMI (i.e. at ART initiation), remain active in the program for at least six months, and have a follow-up weight measurement within the six-month window period. In the analyses of death or treatment failure, patients were censored at the time of voluntary withdrawal from the program or when classified as lost to follow-up (defined as 37 days after a scheduled pharmacy visit or, if no pharmacy visit was scheduled, 60 days after the last clinical visit). We compared the demographic and medical characteristics of those included and excluded from the analysis. For dichotomous or categorical variables, we calculated percentages; for continuous descriptors, we calculated means and standard deviations. We calculated mortality rates in person-years and generated corresponding exact Poisson confidence intervals for each estimate.
For our primary analysis, we categorized patients according to weight gain across two measures: absolute weight change from ART initiation to six months (≥10.00 kg, 5.00 – 9.99 kg, 2.50 – 4.99 kg, 0.00 – 2.49 kg, weight loss) and proportional weight change from ART initiation to six months (≥20.0%, 10.0 – 19.9%, 0.0 – 9.9%, weight loss). For each of these groups, we examined the risk of death and clinical treatment failure from six months onward, using Kaplan-Meier analysis and Cox Proportional Hazards models. For this analysis, we defined treatment failure as a worsening WHO stage after at least three months on therapy, a decline in the CD4+
lymphocyte count to a value <95% of the pre-treatment baseline, and/or a change to second-line treatment. Multivariable models were adjusted for age, gender, baseline hemoglobin, tuberculosis status, baseline WHO stage, initial ART regimen, and adherence. Adherence was based on the medication possession ratio defined as the number of days late for pharmacy refills divided by the total days on therapy, subtracted from 100%. The resulting figure represents the percentage of days a patient is known to have medication 14
. Because entry BMI is a known effect modifier 3, 8, 9
, we performed stratified analyses according to the above-mentioned WHO categories for malnutrition 7
. We also included a weighted hazard ratio in our Cox Proportional Hazards model, to provide a summary measure based on the distribution of BMI in our population.
Available patient data through October 31, 2008 (the dataset freeze date) were considered in this report. All analyses were performed using SAS version 9.1 (SAS Institute, Cary, North Carolina), and were approved by the relevant ethical authorities of the University of Zambia (Lusaka, Zambia) and the University of Alabama at Birmingham (Birmingham, Alabama, USA).