Years after their body weight stabilized, HIV-positive men with a wasting history had significantly lower grip strength than HIV-positive men who never had wasting, according to a Multicenter AIDS Cohort Study (MACS) analysis. Men with wasting in the past also reported worse physical quality of life (QoL) than HIV-positive or negative men without wasting, but immune suppression explained much of that impact.
Wasting characterized by loss of both fat mass and lean body mass emerged as an early hallmark of AIDS. Although wasting incidence dropped sharply with the arrival of potent antiretroviral therapy (ART), otherwise effective ART may not lead to fully restored total body weight or lean body mass. And wasting remains a threat to people who start antiretroviral therapy with a low CD4+ count. Because the long-term impact of HIV wasting on health in ART responders remains poorly understood, MACS investigators conducted this three-way comparison.
Begun in 1984, the MACS is a prospective observational study at four U.S. sites of HIV-positive and at-risk HIV-negative men who have sex with men. This analysis focused on HIV-positive men who survived at least two years after a clinical diagnosis of wasting or standard weight criteria indicating wasting. The investigators matched each man with wasting to three HIV-positive men without wasting and up to four HIV-negative men without wasting. Cases with wasting and controls without wasting were matched by age, calendar time, and (in men with HIV) CD4+ count and viral load above or below 400 copies/mL. Control study visits occurred within a year of the case's wasting diagnosis. There were four outcome measures based on testing done at semiannual MACS visits: grip strength, time to walk four meters, and composite physical and mental health measures from a standard health-related QoL test (SF-36). Linear regression analysis to assess the impact of wasting on these outcomes considered age, race, hepatitis C status, number of comorbidities and MACS cohort (before 2001 or 2001–2003).
The analysis included 85 HIV-positive men with wasting, 249 HIV-positive men without wasting and 338 HIV-negative men without wasting. Median age was 46 or 47 years in all three groups. In the two HIV groups, current and nadir CD4+ counts were lower in the wasting group, and the wasting group had a lower proportion of study visits with a viral load below 400 copies/mL (82% versus 91%). HIV-positive men with wasting also had a higher median number of comorbidities than HIV-positive men without wasting (2 versus 1).
A median of 4.1 years elapsed between the wasting diagnosis visit and functional outcome measures. Men with wasting weighed 10 kg less than men in the other two groups at the wasting visit, and still weighed 8 to 9 kg less at the outcome test visit. Multiple linear regression analysis including all men with and without HIV determined that men with a wasting history had lower grip strength and worse physical QoL than HIV-positive men without wasting, and worse physical QoL than HIV-negative men without wasting (grip strength HIV+ no wasting versus HIV+ wasting estimate 2.4, 95% confidence interval [CI] 0.2 to 4.7, P = .03; physical QoL HIV+ no wasting vs HIV+ wasting estimate 2.8, 95% CI 0.5 to 5.1, P = .016; physical QoL HIV- versus HIV+ wasting estimate 4.8, 95% CI 2.5 to 7.0, P < .001). Mental QoL was better in HIV-positive men with wasting than in HIV-negative men (mental QoL HIV- versus HIV+ wasting estimate –2.7, 95% CI –5.4 to 0, P = .05). Walking time did not differ significantly between men with versus without wasting.
In regression models limited to men with HIV and adjusted for nadir CD4+ count and clinical AIDS, the associations between wasting and physical QoL and between wasting and grip strength became attenuated and nonsignificant. In other words, prior immune suppression largely explained the association between wasting and these outcomes. No HIV variables predicted grip strength, walking time or mental QoL. Mental QoL was negatively associated with more comorbid diseases. Older age predicted all outcomes.
The MACS investigators suggest that the greater impact of wasting on grip strength and physical QoL than on walking time may reflect lost lean mass that men with wasting failed to regain. They calculated that the grip strength loss linked to wasting is similar to the grip strength lost during five year of aging. The researchers believe their findings suggest that "HIV-infected survivors of wasting may represent a population of adults at increased risk for physical function decline." They encourage clinicians to monitor HIV patients for a falling weight trajectory.