scholarly journals Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor–Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada

Author(s):  
Peter F Rebeiro ◽  
Cathy A Jenkins ◽  
Aihua Bian ◽  
Jordan E Lake ◽  
Kassem Bourgi ◽  
...  

Abstract Background Integrase strand transfer inhibitor (INSTI)–based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)–, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92–1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07–1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06–1.91]) vs NNRTI initiators. The INSTI–DM association was attenuated (HR, 1.03 [95% CI, .71–1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S508-S508
Author(s):  
Yesha Patel ◽  
Sheila Okere ◽  
Mark Lustberg ◽  
Carlos Malvestutto

Abstract Background Obesity is a global public health crisis with a growing prevalence in persons with human immunodeficiency virus (PWH) population. In this study, we aimed to investigate factors associated with weight gain in the PWH population. Methods This was a single-centered, retrospective cohort study of our clinic patient population from January 1, 2015 to January 1, 2019. Patients with human immunodeficiency virus (HIV) were identified from the electronic health record and a randomized sample of 300 patients who had at least two follow up appointments, were on antiretroviral therapy, and had viral loads less than 200 were evaluated. The primary outcome was weight change over follow up. Cox Proportional Hazards models were used, taking a weight gain > 3 kg as the outcome, and the time on therapy between visits as the time to event. Robust linear regression was used to model mean changes in weight, accounting for influential observations. All analysis were performed in STATA 16.0. Table 1 Results At baseline, 87% were male, 63% were white, and 65% were overweight/obese. 30% were on a protease inhibitor, 46% were on non-nucleoside reverse transcriptase inhibitor, and 37% were on an integrase inhibitor. 64% were on Tenofovir disoproxil (TDF), 8% were on Tenofovir alafenamide (TAF), and 19% were on Abacavir. Mean weight change over follow up was significantly increased at 1.31 kg (95% CI = 0.58 – 2.04 kg, p= 0.0004). TAF use and male gender were significantly associated with risk of weight gain > 3 kg in univariate analysis [respectively, OR = 2.53, 95% CI = 1.30 – 4.92, p = 0.006; OR = 2.60, 95% CI = 1.05 – 6.45, p = 0.04]. In multivariate analysis, TAF use was significantly associated with weight gain > 3 kg, while male gender was of borderline significance [respectively, OR = 2.29, 95% CI = 1.17 – 4.47, p = 0.01; OR = 2.40, 95% CI = 0.96 – 5.97, p=0.060]. Significant factors associated with weight change are noted in Table 1. Conclusion As PWH are living longer on effective ARV therapy, monitoring for weight gain is required as obesity contributes to morbidity and mortality from cardiovascular disease and metabolic diseases. Key factors for weight gain in our clinic population include male gender, baseline diagnosis of hypertension, use of TAF, bictegravir use, and rilpivirine use. Disclosures Carlos Malvestutto, MD, Gilead Sciences (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member)


2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Anton Reepalu ◽  
Taye Tolera Balcha ◽  
Sten Skogmar ◽  
Zelalem Habtamu Jemal ◽  
Erik Sturegård ◽  
...  

Abstract Background.  Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in human immunodeficiency virus (HIV)/TB-coinfected patients. We compared virological suppression (VS) rates, mortality, and retention in care in HIV-positive adults receiving care in 5 Ethiopian health centers with regard to TB coinfection. Methods.  Human immunodeficiency virus-positive ART-naive adults eligible for ART initiation were prospectively recruited. At inclusion, all patients underwent microbiological investigations for TB (sputum smear, liquid culture, and polymerase chain reaction). Virological suppression rates after 6 months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB coinfection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models. Results.  Among 812 participants (TB, 158; non-TB, 654), 678 started ART during the follow-up period (TB, 135; non-TB, 543). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died, and 17 (2.5%) were lost to follow-up (P = .30 and P = .83, respectively). Overall rates of VS at 6 months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB coinfection (<40 copies/mL: 65 of 92 [70.7%] vs 304 of 420 [72.4%], P = .74; <400 copies/mL: 77 of 92 [83.7%] vs 377 of 420 [89.8%], P = .10, respectively). Conclusions.  High rates of VS can be achieved in adults receiving ART at health centers, with no significant difference with regard to TB coinfection. These findings demonstrate the feasibility of combined ART and anti-TB treatment in primary healthcare in low-income countries. Clinical Trials Registration.  NCT01433796.


Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1377
Author(s):  
Giancarlo Ceccarelli ◽  
Marta Giovanetti ◽  
Caterina Sagnelli ◽  
Alessandra Ciccozzi ◽  
Gabriella d’Ettorre ◽  
...  

West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but a high number of cases has been recognized in Europe, India, and the United States. The virus is less transmissible than HIV-1, with sexual contacts being the most frequent route of acquisition. In the absence of specific antiretroviral therapy, most HIV-2 carriers will develop AIDS. Although, it requires more time than HIV-1 infection, CD4+ T cell decline occurs more slowly in HIV-2 than in HIV-1 patients. HIV-2 is resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors. Misdiagnosis of HIV-2 in patients mistakenly considered HIV-1-positive or in those with dual infections can cause treatment failures with undetectable HIV-1 RNA. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we focus mainly on data available and on the insight they offer about molecular epidemiology, clinical presentation, antiretroviral therapy, and diagnostic tests of HIV-2 infection.


2018 ◽  
Vol 68 (6) ◽  
pp. 1048-1051 ◽  
Author(s):  
Nagalingeswaran Kumarasamy ◽  
Sandeep Prabhu ◽  
Ezhilarasi Chandrasekaran ◽  
Selvamuthu Poongulali ◽  
Amrose Pradeep ◽  
...  

AbstractIn this first study of generic dolutegravir (DTG)-containing regimens in a low-resource setting, we assessed safety, tolerability, and efficacy within a prospective cohort of 564 patients with at least 6 months of clinical follow-up. We provide support for a large-scale transition to DTG as part of first-line regimens.


2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Romuald Cruchet ◽  
Lorenza N C Dezanet ◽  
Sarah Maylin ◽  
Audrey Gabassi ◽  
Hayette Rougier ◽  
...  

Abstract Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.


Author(s):  
Shannon L. Turvey ◽  
Sean M. Bagshaw ◽  
Dean T. Eurich ◽  
Wendy I. Sligl

Purpose.The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality.Materials and Methods.Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality.Results.Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3(30–300) and 28,000 copies/mL (110–270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08–1.16;p<0.001), cirrhosis (aHR 2.30; 95% CI 1.12–4.73;p=0.024), coronary artery disease (aHR 6.98; 95% CI 2.20–22.13;p=0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02–1.13;p=0.01). CD4 count and PVL were not associated with mortality.Conclusions.Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.


Author(s):  
Lene Ryom ◽  
Jens D Lundgren ◽  
Peter Reiss ◽  
Mike Ross ◽  
Ole Kirk ◽  
...  

Abstract Background Relations between different measures of human immunodeficiency virus–related immunosuppression and chronic kidney disease (CKD) remain unknown. Methods Immunosuppression measures included baseline, current, time-lagged and nadir CD4, years and percentage of follow-up (%FU) with CD4 ≤200 cells/μL, and CD4 recovery. CKD was defined as confirmed estimated glomerular filtration rate &lt;60 mL/minute/1.73 m2. Results Of 33 791 persons, 2226 developed CKD. Univariably, all immunosuppression measures predicted CKD. Multivariably, the strongest predictor was %FU CD4 ≤200 cells/μL (0 vs &gt;25%; incidence rate ratio [IRR], 0.77 [95% confidence interval [CI], .68–.88]), with highest effect in those at low D:A:D CKD risk (IRR, 0.45 [95% CI, .24–.80]) vs 0.80 [95% CI, .70–.93]). Conclusions Longer immunosuppression duration most strongly predicts CKD and affects persons at low CKD risk more.


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