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.
ABSTRACT
OBJECTIVES: The aim of the study was to describe patient characteristics and outcomes among HIV-positive adults presenting to a Zambian tertiary care hospital with new-onset seizures. METHODS: From July 2011 to June 2013, adults with seizures and a known or probable diagnosis of HIV infection were screened for a cohort study. Demographic and clinical data were obtained, including information on engagement in HIV services and in-patient mortality. Analyses were conducted to identify characteristics associated with poor engagement in care and death. RESULTS: A total of 320 of 351 screened adults were HIV-positive, with 268 of 320 experiencing new-onset seizures. Of these, 114 of 268 (42.5%) were female, and their mean age was 36.8 years. Seventy-nine of the 268 patients (29.5%) were diagnosed with HIV infection during the index illness. Among those who were aware of their HIV-positive status, 59 of 156 (37.8%) had disengaged from care. Significant functional impairment (Karnofsky score < 50) was evident in 44.0% of patients. Cerebrospinal fluid was not obtained in 108 of 268 (40.3%). In-patient mortality outcomes were available for 214 patients, and 47 of these 214 (22.0%) died during hospitalization. Patients with significant functional impairment were more likely to undergo lumbar puncture (P = 0.046). Women and the functionally impaired were more likely to die (P = 0.04 and < 0.001, respectively). CONCLUSIONS: Despite the availability of care, less than half of HIV-infected people with new-onset seizures were actively engaged in care and in-patient mortality rates were high. In the absence of clinical contraindication, lumbar puncture should be performed to diagnose treatable conditions and reduce morbidity and mortality. Continued efforts are needed to expand community-based testing and improve HIV care retention rates. Qualitative studies are needed to elucidate factors contributing to lumbar puncture usage in this population.
