A study published in the April 27th issue of AIDS indicates that weight gain may be a reliable predictor of survival in underweight men and women starting antiretroviral therapy. The finding has broad implications because resource limitations in many developing countries preclude the use of laboratory monitoring to assess treatment effectiveness. If healthcare providers have some other means of identifying which patients are responding poorly to antiretroviral regimens, they may be able to intervene before those patients become dangerously ill.
The cohort study analysed mortality rates six and twelve months after the initiation of antiretroviral therapy. Study participants were being treated in Médecins Sans Frontières (MSF) programmes in Phnom Penh, Cambodia and Homa Bay, Kenya. The most striking finding was that people who had an initial body mass index (BMI) score of 18.5 kg/m2 or less and experienced weight gains of 10% or less during the first three months of antiretroviral therapy were far more likely to die within the next three months than people who had comparable initial BMI scores but experienced greater weight gains.
The study population was comprised of 2451 Cambodian adults and 2618 Kenyan adults. MSF followed World Health Organization (WHO) recommendations for initiating antiretroviral therapy: people offered antiretrovirals had either a WHO stage 4 condition, a WHO stage 3 condition with a CD4 cell count of less than 350 cells/mm3, or a CD4 cell count of less than 200 cells/mm3.
All antiretroviral regimens consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). In Cambodia, 51% of study participants received 3TC (lamivudine, Epivir), d4T (stavudine, Zerit), and nevirapine (Viramune), while 47% received 3TC, d4T, and efavirenz (Sustiva). In Kenya, 86% of people received the nevirapine-containing regimen, and 9% received the efavirenz-containing regimen.
The study evaluated the prognostic value of weight gain using four categories of initial BMI scores: ≤17 kg/m2; >17 to ≤18.5 kg/m2; >18.5 to ≤20 kg/m2; and >20 kg/m2. Individuals in the first two categories are considered underweight by international standards. Mortality was analysed in relation to three levels of BMI increase at three months and six months: ≤5%; >5% to ≤10%; and >10%. Weight gain was found to be predictive of survival for study participants with initial BMI scores in the lower two quartiles, i.e., those who were underweight. People with an initial BMI score of ≤18.5 kg/m2 and weight gain of ≤5% had a mortality rate ratio (MRR) of 6.3 when compared to those in the same initial BMI category with weight gain of >10% (95% confidence interval [CI], 3.0 – 13.1).
The MRR for people with an initial BMI score of ≤18.5 kg/m2 and weight gain of >5% to ≤10% was 3.4 when compared to those in the same initial BMI category with weight gain of >10% (95% CI, 1.4 – 8.3).
When the researchers compared the prognostic value of weight gain in men and women, they found no significant differences. Nor were there differences between Kenyans and Cambodians; between people who started antiretroviral therapy at different disease stages or CD4 count levels; or between people using different antiretroviral regimens. All of this indicates that tracking weight over time can be an effective strategy in a wide range of antiretroviral recipients.
Weight gain was not predictive of survival for people whose initial BMI score was higher than 18.5 kg/m2. This somewhat lessens the value of weight monitoring as a clinical management tool. However, given that many people in resource-limited settings do not begin treatment until relatively late in the course of HIV disease, low BMI scores at treatment initiation are not uncommon. Forty-six percent of Cambodian study participants and almost forty percent of Kenyan study participants had BMI scores of 18.5 kg/m2 or less.
“Weight gain can be of great use in resource-limited settings, especially when decentralization of HIV care is required and access to well-trained physicians is limited,” the authors conclude. They go on to note that three possible reasons for an HIV-positive person’s failure to put on weight after initiating antiretroviral therapy are poor medication adherence, opportunistic infections, and insufficient nutritional intake. They advise assessing adherence and providing adherence counselling as warranted.
The authors express particular concern about the importance of screening for tuberculosis (TB) in antiretroviral non-responders, noting, “The experience from MSF in five countries showed a high incidence of TB under [antiretroviral therapy], and TB remains a leading cause of death in resource-limited settings.”
The authors stress that identifying antiretroviral non-responders by tracking weight should only be regarded as an interim solution. “Our results should not be interpreted as advocacy for minimal care and monitoring of patients taking ART in developing countries,” they write. “CD4 cell count and viral load remain the gold standards for patient monitoring, and everything should be done to make these tests available in resource-limited settings.”
Madec Y et al. Weight gain at three months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS 23: 853–861, 2009.