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Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia
Global Health Sciences Literature Digest
Published November 30, 2010
Journal Article

Koethe JR, Lukusa A, Giganti MJ, Chi BH, Nyirenda CK, Limbada MI, et al. Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2010 Apr 1;53(4):507-13

In Context

Being malnourished may make responding to antiretroviral therapy (ART) more difficult. Several studies have shown that persons on ART with a low initial body mass index (BMI) have a higher mortality.(1, 2, 3) There have been several trials of supplementary feeding, but these found inconsistent improvements in weight and no survival benefit.(4) Supplementary feeding may improve medication adherence and patient retention, however.(5)

Objective

To determine the association of 6-month weight gain on clinical outcomes and mortality among adults on ART.

Setting

Public health sector clinics in Lusaka District, Zambia

Study Design

Observational cohort

Population

HIV infected adults >15 years of age

Methods

Data was analyzed from a cohort of HIV-infected adults who started ART between May 2004 and April 2008; follow-up data was analyzed through end-October 2008. ART eligibility, treatment and follow-up were per national guidelines. Patients were included in analyses if they had a baseline BMI, remained in treatment for at least 6 months and had follow-up weights recorded. Patients were categorized based on absolute weight, and percentage weight change from ART initiation to 6 months. Mortality and clinical treatment failure after the initial 6-month period was analyzed. Clinical failure was considered as a worsening WHO stage, a decrease in CD4 cell count to <95% of baseline, or a change to second-line treatment. Multivariable models were adjusted for age, gender, baseline hemoglobin (Hgb), TB status, baseline WHO stage, initial ART regimen, and adherence. BMI was calculated as weight in kg divided by height in meters squared (kg/m2). WHO grading of malnutrition was based on BMI: no malnutrition (BMI ≥18.5 kg/m2), mild malnutrition (17-18.49), moderate (16-16.99), and severe (<16). Stratified analyses were performed within each of the categories of malnutrition.

Results

Out of 46,159 patients who started ART, 2933 died before 6 months and 27,915 were eligible for long-term analysis. At baseline, lower median CD4 count, lower Hgb, higher prevalence of TB, and more severe WHO stage occurred progressively with lower BMI. Evaluation of absolute weight gain by baseline BMI strata showed that 39% of those with lowest BMI (<16 kg/m2 BMI) were most likely to gain >10 kg, compared to 25% of those with BMI 16-16.99, 16% of those 17-18.49 kg/m2, 8.5% of those >18.5 kg/m2. Within the first 3 months, mortality was highest among those with the lowest BMI (80 deaths per 100 person years [p100py]), and decreased with higher BMI (47 p100py, 27 p100py, and 13 p100py among increasing BMI strata, respectively). Mortality after 6 months showed that those who lost weight had the greatest risk of death, particularly among those with BMI <16.0 kg/m2 (AHR=9.7, 95% CI: 4.7,20.0); those who had the highest BMI at baseline but who lost weight also had an increased risk of death (AHR=2.1, 95% CI: (1.4,3.1)). Results were similar for changes in weight associated with clinical treatment failure.

Conclusions

Weight gain within the first 6 months of ART is associated with better clinical outcomes and lower mortality, even when controlling for baseline BMI. Those who gained at least 5 kg within the first 6 months had improved outcomes. It is possible that a minimum weight gain within the first 6 months may improve outcomes.

Study Quality

This was a high-quality observational study. However, 12% of patients lacked weight data and only 69% of the overall sample could be analyzed. Those who lacked 6-month data because they were lost to follow-up or withdrew and were therefore not analyzed had clinically worse disease at baseline.

Programmatic Implications

This study suggests that gaining weight after ART initiation may improve longer term response to ART (after 6 months), particularly in reducing mortality. However, the direction of causality cannot be determined from this study-in other words, it is not clear whether a response to ART resulted in the weight gain, rather than an increased weight causing improved ART outcomes. Regardless, clinicians may want to monitor changes in weight in addition to BMI when starting patients on ART to identify those most at risk, and to provide referrals for nutritional supplementation, particularly among those with a low BMI.

References

  1. Coetzee D, Hildebrand K, Boulle A, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS. 2004;18:887-895.
  2. Stringer JS, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006; 296:782-793.
  3. Zachariah R, Fitzgerald M, Massaquoi M, et al. Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi. AIDS. 2006;20:2355-2360.
  4. Johannessen A, Naman E, Ngowi BJ, et al. Predictors of mortality in HIVinfected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infect Dis. 2008;8:52.
  5. Mahlungulu S, Grobler LA, Visser ME, et al. Nutritional interventions for reducing morbidity and mortality in people with HIV. Cochrane Database Syst Rev. 2007;(3):CD004536.