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Changes in plasma lipidome following initiation of antiretroviral therapy.

ABSTRACT: INTRODUCTION:HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen. METHODS:Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed. RESULTS:Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species. CONCLUSIONS:Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz.

SUBMITTER: Trevillyan JM

PROVIDER: S-EPMC6114786 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description:IntroductionWeight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV-positive individuals.MethodsThis was a prospective cohort study of 13,198 subjects included in the Spanish HIV Research Network (CoRIS) between January 2004 and November 2018. We included subjects who started triple ART and achieved HIV RNA suppression within 48 weeks. We fitted linear mixed models adjusted for potential confounders to compare longitudinal changes in weight. We used Cox proportional-hazard models to compare treatment groups' times to transition to a higher body mass index (BMI) category.ResultsWe analysed data from a total of 1631 individuals resulting in 14,965 persons/years and 14,085 observations. Individuals retained in the final multivariable model were representative of the overall cohort. NNRTI-based first-line ART was associated with a lower average weight gain compared to PI- (+0.7 kg per year, 95% CI 0.5 to 1.0, p < 0.001) and INSTI-based (+0.9 kg per year, 95% CI 0.7 to 1.1, p < 0.001) regimens. Individuals starting ART with TAF+FTC had greater weight gain than those receiving TDF+FTC (+0.8 kg per year, 95% CI 0.3 to 1.4, p = 0.004). Women and black persons presented a greater weight gain than men and non-black individuals. Differences in weight trajectories were driven mainly by changes during the first year of ART. The NNRTI group was less likely to transition from normal weight to overweight than the PI (aHR 1.48, 95% CI 1.18 to 1.85) and INSTI groups (aHR 1.30, 95% CI 1.03 to 1.64). PIs but not INSTIs were associated with a higher rate of overweight-to-obesity shift (aHR 2.17, 95% CI 1.27 to 3.72). No differences were found among INSTIs in the transition to a higher BMI category.ConclusionsINSTI- and PI-based first-line ARTs are associated with greater weight gain compared to NNRTI-based ART. Within the NRTIs, TAF+FTC was most strongly associated with weight gain. This heterogeneous effect of ART on body weight could affect the long-term risk of some non-communicable diseases.

Project description:BackgroundPapua Province, Indonesia is experiencing an on-going epidemic of Human Immunodeficiency Virus (HIV) infection, with an estimated 9-fold greater prevalence than the overall national rate. This study reviewed the treatment outcomes of an HIV-infected cohort on Antiretroviral Therapy (ART) and the predictors in terms of immunological recovery and virological response.MethodsART-naïve individuals in a workplace HIV program in southern Papua were retrospectively analyzed. Patients were assessed at 6, 12 and 36 months after ART initiation for treatment outcomes, and risk factors for virological suppression (viral load (VL) <1,000 copies/ml), poor immune response (CD4 <200 cells/mm3) and immunological failure (CD4 <100 cells/ mm3) after at least 6 months on ART, using a longitudinal Generalized Estimating Equations multivariate model.ResultsAssessment of 105 patients were included in the final analysis with a median age of 34 years, 88% male, median baseline CD4 236 cells/ mm3, and VL 179,000 copies/ml. There were 74, 73, and 39 patients at 6, 12, and 36 months follow-up, respectively, with 5 deaths over the entire period. For the three observation periods, 68, 80, and 75% of patents achieved virological suppression, poor immune responders decreased from 15, 16 to 10%, whilst 15, 16, 10% met the immunological failure criteria, respectively. Using multivariate analysis, the independent predictor for viral suppression at 12 and 36 months was ≥1 log decrease in VL at 6 months (OR 19.25, p<0.001). Higher baseline CD4 was significantly correlated with better immunological outcomes, and lower likelihood of experiencing immunological failure (p <0.001).ConclusionVirological response at six months after beginning ART is the strongest predictor of viral suppression at 12 and 36 months, and may help in identifying patients needing additional adherence therapy support. Higher baseline CD4 positively affects the immunological outcomes of patients. The findings indicate HIV control programs should prioritize the availability of VL testing and begin ART regardless of CD4 counts in infected patients.

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Changes in plasma lipidome following initiation of antiretroviral therapy.

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