Dataset Information

Lower Cumulative Antiretroviral Exposure in People Living With HIV and Diabetes Mellitus.

ABSTRACT:

Objective

People living with HIV (PLWH) are living longer and developing more non-AIDS comorbidities, which negatively impact antiretroviral therapy (ART) adherence. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a novel pharmacologic measure of cumulative ART adherence that is predictive of viral suppression and future viremia. However, the relationship between non-AIDS comorbidities and this adherence measure is unknown. We aimed to evaluate the association between 3 non-AIDS comorbidities (diabetes mellitus (DM), hypertension, and hyperlipidemia) and TFV-DP in DBS in PLWH.

Methods

Blood for TFV-DP in DBS and HIV viral load was prospectively collected from PLWH on tenofovir disoproxil fumarate for up to 3 times over 48 weeks. Non-AIDS comorbidities were recorded. Mixed effect multivariable linear regression models were used to estimate the changes in TFV-DP concentrations in DBS according to the presence of comorbidities and to estimate the percent differences in TFV-DP concentrations between these groups.

Results

A total of 1144 person-visits derived from 523 participants with available concentrations of TFV-DP in DBS were included in this analysis. In univariate analysis, no significant association between non-AIDS comorbidities (categorized as having 0, 1, 2, or 3 comorbidities) and the concentrations of TFV-DP in DBS was observed (P = 0.40). Participants who had DM had 25% lower (95% confidence interval: -36% to -12%; P < 0.001) TFV-DP in DBS than participants without DM after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4 T-cell count, hematocrit, ART class, patient-level medication regimen complexity index, and 3-month self-reported adherence.

Conclusions

Diabetic PLWH have lower concentrations of TFV-DP in DBS compared with those without DM. Further research is required to identify the clinical implications and biological mechanisms underlying these findings.

SUBMITTER: Mann SC

PROVIDER: S-EPMC7756101 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Lower Cumulative Antiretroviral Exposure in People Living With HIV and Diabetes Mellitus.

Mann Sarah C SC Morrow Mary M Coyle Ryan P RP Coleman Stacey S SS Saderup Austin A Zheng Jia-Hua JH Ellison Lucas L Bushman Lane R LR Kiser Jennifer J JJ MaWhinney Samantha S Anderson Peter L PL Castillo-Mancilla Jose R JR

Journal of acquired immune deficiency syndromes (1999) 20201201 4

<h4>Objective</h4>People living with HIV (PLWH) are living longer and developing more non-AIDS comorbidities, which negatively impact antiretroviral therapy (ART) adherence. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a novel pharmacologic measure of cumulative ART adherence that is predictive of viral suppression and future viremia. However, the relationship between non-AIDS comorbidities and this adherence measure is unknown. We aimed to evaluate the association between 3 non- ...[more]

PMID: 33136749

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Project description:BackgroundFollowing reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG.MethodsBetween January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively.ResultsThe incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): - 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: - 7.26 mg/dl, IQR: - 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36.ConclusionWe demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Project description:Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve.

Project description:BackgroundDue to the complexity of human diets, it is difficult to relate single foods to health outcomes. We aimed to identify the dietary patterns and associated factors and to assess the association of dietary patterns with prediabetes/diabetes among adults living with and without HIV in Tanzania.MethodsDiet data were collected by a food frequency questionnaire (FFQ) and dietary patterns were derived by principal component analysis (PCA) and reduced rank regression (RRR). The associations between dietary patterns and associated factors as well as with prediabetes/diabetes were assessed using multinomial logistic regression and presented by marginal plots.ResultsOf 572 recruited, 63% were people living with HIV. The mean (±SD) age was 42.6 (±11.7) years and 60% were females. The PCA identified two major dietary patterns, i.e., vegetable-rich pattern (VRP) and vegetable-poor pattern (VPP) whereas RRR identified one dietary pattern, i.e., carbohydrate-dense pattern (CDP). In comparison to females, males had higher adherence to VPP and CDP, but less to VRP. Higher socioeconomic status was associated with higher adherence to VRP and VPP but low adherence to CDP. Compared to HIV-negative participants, people living with HIV had higher adherence to VRP but less adherence to CDP. Compared to younger people, older people had lower adherence to VPP. High adherence to CDP or VRP was positively associated with prediabetes. Higher adherence to VRP was associated with a borderline decrease in diabetes. No association was observed between VPP with either prediabetes or diabetes.ConclusionOur findings suggest that dietary patterns may impact the risk of prediabetes and diabetes differently. Awareness of the health benefits of VRP should be encouraged in the community, especially for men who seem to consume fewer vegetables. Longitudinal studies are needed to explore the contribution of dietary patterns to prediabetes/diabetes development in sub-Saharan Africa.

Dataset Information

Lower Cumulative Antiretroviral Exposure in People Living With HIV and Diabetes Mellitus.

Objective

Methods

Results

Conclusions

Publications

Lower Cumulative Antiretroviral Exposure in People Living With HIV and Diabetes Mellitus.

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