abacavir and Vitamin-D-Deficiency

The prevalence of vitamin D insufficiency in Africans with AIDS-associated Kaposi sarcoma (AIDS-KS) and the role of vitamin D in AIDS-KS progression are unknown. We hypothesized that a high prevalence of vitamin D deficiency would be found in Zimbabweans with AIDS-KS and that low baseline vitamin D would correlate with progression of AIDS-KS.. Ninety subjects were enrolled in a prospective pilot study investigation of the effect of antiretroviral therapy in the treatment of AIDS-KS in Harare, Zimbabwe. Co-formulated abacavir, lamivudine, and zidovudine was initiated; chemotherapy was provided at the discretion of the provider. Participants were followed for 96 weeks. 25-Hydroxyvitamin D was measured in stored specimens collected at study entry. The relationship between vitamin D and clinical response was described by odds ratio and 95% confidence interval.. Samples were available for 85 participants; 45 (53%) subjects had inadequate (<75 nmol/l) 25-hydroxyvitamin D. HIV-1 RNA was significantly higher among those with insufficient vitamin D (4.7 vs. 4.5 log, p = 0.04). Tumor response, survival, and KS-IRIS were not associated with vitamin D (p ≥ 0.3).. Vitamin D insufficiency was common among Zimbabweans with AIDS-KS but not associated with outcomes after initiation of antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Dideoxynucleosides; Disease Progression; Female; Herpesvirus 8, Human; HIV-1; Humans; Lamivudine; Male; Middle Aged; Odds Ratio; Pilot Projects; Prospective Studies; RNA, Viral; Sarcoma, Kaposi; Survival Analysis; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Zidovudine; Zimbabwe

Initiation of combined antiretroviral therapy (cART) is associated with bone loss, which may be more intense with regimens including tenofovir. The underlying mechanisms are not well understood. Cross-sectional data have linked tenofovir with higher parathyroid hormone (PTH) concentrations in patients with vitamin D deficiency. We performed a longitudinal study with a 48-week follow-up to evaluate sequential changes in PTH and 25-hydroxyvitamin D [25(OH)D] levels in patients starting cART with either tenofovir/emtricitabine or abacavir/lamivudine. Fifty-seven patients were included, 31 initiating tenofovir/emtricitabine and 26 initiating abacavir/lamivudine. Median PTH levels turned out to be significantly higher among tenofovir/emtricitabine users at week 4 (p=0.01), week 24 (p=0.008), and week 36 (p=0.02), and were above the upper limits of normal values (ULN) at weeks 24, 36, and 48 only in patients receiving tenofovir/emtricitabine. 25(OH)D, serum and urine calcium and phosphate, and renal-tubular maximum reabsorption of phosphate to the glomerular filtration rate (TmP/GFR) levels did not differ between the two treatment arms over the study period. Among tenofovir/emtricitabine users, median (interquartile range) PTH concentrations were significantly higher in patients with suboptimal 25(OH)D levels (<30 μg/liter) at week 24 [63 (57.8-82.4) ng/liter vs. 54.3 (34.4-63.067.5) ng/liter, p=0.05] and week 48 [67.5 (59.6-86.0) ng/liter vs. 41.9 (37.3-68.8) ng/liter, p=0.03]. A multivariable logistic regression model showed that tenofovir/emtricitabine use was an independent predictor of high PTH levels (≥53 ng/liter). Starting cART with tenofovir regimens is associated with an elevation in PTH plasma concentrations soon after introducing the drug. Suboptimal baseline 25(OH)D levels increase the risk of developing secondary hyperparathyroidism among tenofovir users.

Topics: Adenine; Adult; Anti-HIV Agents; Bone Density; Deoxycytidine; Dideoxynucleosides; Emtricitabine; Female; Follow-Up Studies; HIV Seropositivity; Humans; Lamivudine; Longitudinal Studies; Male; Organophosphonates; Parathyroid Hormone; Tenofovir; Vitamin D; Vitamin D Deficiency