Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors

Abstract

Background: Cachexia is usually associated with elevated serum interleukin-6 (IL-6) as it stimulates the breakdown of muscle proteins and promotes wasting. Objective: A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. Methods: IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). Results: A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1–2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). Conclusion: HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.