Abstract

Background: As HIV-positive persons survive longer due to the success of combination antiretroviral therapy (ART) in decreasing mortality, the burden of non-communicable diseases including diabetes mellitus (DM) is anticipated to rise. HIV is characterized by systemic inflammations, markers of which decrease quickly following ART initiation, but typically do not completely normalize. Inflammation may be accompanied by insulin resistance (IR), and both are implicated in the pathogenesis of DM in HIV-positive individuals. Sub-Saharan Africa accounts for almost two-thirds of the global HIV burden but there are few reports of IR, DM and HIV in this region. We assessed the relationship between IR and viral suppression among HIV-positive adults in the Zambian national ART program.

Methods: We conducted a cross-sectional survey evaluating HIV-positive adults that had received first line ART (usually TDF/FTC/EFV) for 12 months (± 3 months). Twenty clinics were sampled systematically based on the random starting-point, sampling interval and cumulative population size. Eligible patients had plasma viral load (VL), fasting insulin, and glucose performed. Insulin resistance was determined using Homeostatic model assessment (HOMA). We determined proportions for each outcome using linearized standard error 95% confidence intervals and summary estimates. Viral suppression was defined according to the detection threshold of<20 copies/mL and treatment failure was defined as VL>1,000 copies/mL.

Results: Of 473 patients enrolled, 46.8% were male and 53.2% were female. 142 (30%) [95% CI: 0.26-0.34] had IR. Among those with IR, 55 (38.7%) were male whereas 87 (61.3%) were female (p value=0.104). 19% of individuals with IR had treatment failure compared to 5.7% without IR (p value<0.0001). 427 (90.3%) participants had treatment success (VL<1,000 copies/mL), and this was associated with a lower likelihood of IR (odds ratio (OR)=0.26 [0.14, 0.48], p value<0.0001). In addition, a significantly lower proportion of patients with IR were virologically suppressed at one-year compared to individuals without IR, 58% [0.54-0.70] versus 70% [0.65-0.75], respectively (p value=0.042).

Conclusion: In Zambian adults on ART for a year, the development of insulin resistance was strongly associated with suboptimal HIV outcomes, specifically non-viral suppression and treatment failure. Further investigations are warranted to determine if this positive association between IR and VL is causally related, and if so in which direction.

Keywords: Insulin resistance; Combination antiretroviral therapy; Viral suppression; Treatment failure; Zambia