Adverse Effects of Antiretroviral Therapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 12430

Special Issue Editors

Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy
Interests: HIV infection; antiretroviral therapy; HIV non infectious comorbidities; SARS-CoV-2; viral hepatitis in prison setting
Special Issues, Collections and Topics in MDPI journals
Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy
Interests: HIV; antiviral treatment; HIV resistances; zoonotic diseases; SARS-CoV-2; COVID-19; bacterial infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Combination antiretroviral therapy (cART) has dramatically changed the course of HIV infection, both increasing the life expectancy of people living with human immunodeficiency virus (PWH) and improving their quality of life. Current cART regimens, both in naïve and in pre-treated PWH, are effective in reaching very high virological success rates, with minimal differences among different available combinations if measured according to current standards in terms of viral suppression rates and CD4+ increase. Furthermore, since the introduction of integrase strand transfer inhibitors (INSTI)-based regimes, virologic success has reached an even higher plafond, further limiting the possibility to pinpoint differences. However, even when considering its undoubtable successes, cART is not capable of eradicating HIV infection and is still a lifelong treatment. Even with long-term, effective cART, PWH can possibly experience persistent or sporadic low-level viremia, persistent, low-grade inflammation and immune activation. These events are strongly associated with a heightened risk of cardiovascular disease, osteoporosis, frailty, cancer among other non-AIDS-defining events, and may explain the gap in life expectancy in relation to the general population. Furthermore, a progressive weight gain has been observed in PWH receiving cART, especially when an INSTI or tenofovir alafenamide is included in the regimen. In this scenario, further studies are needed to better assess the current impact of non-infectious comorbidities on PWH morbidity and mortality and to better understand their pathophysiological mechanisms.

Prof. Dr. Giordano Madeddu
Dr. Andrea De Vito
Guest Editors

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Keywords

  • combination antiretroviral therapy
  • HIV
  • non-infectious comorbidities
  • cardiovascular disease
  • osteopenia/osteoporosis
  • frailty
  • non-AIDS defining cancer
  • weight gain

Published Papers (5 papers)

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Research

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13 pages, 791 KiB  
Article
Reversibility of Central Nervous System Adverse Events in Course of Art
by Lucia Taramasso, Giancarlo Orofino, Elena Ricci, Barbara Menzaghi, Giuseppe Vittorio De Socio, Nicola Squillace, Giordano Madeddu, Francesca Vichi, Benedetto Maurizio Celesia, Chiara Molteni, Federico Conti, Filippo Del Puente, Eleonora Sarchi, Goffredo Angioni, Antonio Cascio, Carmela Grosso, Giustino Parruti, Antonio Di Biagio and Paolo Bonfanti
Viruses 2022, 14(5), 1028; https://0-doi-org.brum.beds.ac.uk/10.3390/v14051028 - 11 May 2022
Cited by 9 | Viewed by 2112
Abstract
The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards [...] Read more.
The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19–0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)
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11 pages, 1336 KiB  
Article
DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks)
by Carmen Hidalgo-Tenorio, Juan Pasquau, David Vinuesa, Sergio Ferra, Alberto Terrón, Isabel SanJoaquín, Antoni Payeras, Onofre Juan Martínez, Miguel Ángel López-Ruz, Mohamed Omar, Javier de la Torre-Lima, Ana López-Lirola, Jesús Palomares, José Ramón Blanco, Marta Montero and Coral García-Vallecillos
Viruses 2022, 14(3), 524; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030524 - 04 Mar 2022
Cited by 8 | Viewed by 2625
Abstract
Brief: Real-world data in naïve HIV-1 patients demonstrate that dolutegravir plus lamivudine in a multiple tablet regimen is effective, safe, and satisfactory; it causes moderately increasing weight and abdominal circumference and is administrable on a test-and-treat strategy. Background: Our objectives were to determine [...] Read more.
Brief: Real-world data in naïve HIV-1 patients demonstrate that dolutegravir plus lamivudine in a multiple tablet regimen is effective, safe, and satisfactory; it causes moderately increasing weight and abdominal circumference and is administrable on a test-and-treat strategy. Background: Our objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in a multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: An open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with a 48-week follow-up. Results: The study included 88 PLHIV patients (87.5% male) with a mean age of 35.9 years; 76.1% were MSM patients. The mean baseline CD4 was 516.4 cells/uL, with a viral load (VL) of 4.49 log10, and 11.4% were in the AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I + E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had VL < 50 cop/uL by intention-to-treat analysis and 98.7% by per-protocol (PP) analysis. Virological failure (VF) was recorded in 1.1%, with no resistance mutation. One blip was detected in 5.2% without VF. Three reported anxiety, dizziness, and cephalgia, respectively, at week 4 and one reported insomnia at week 24; none reported adverse events at week 48. The mean weight was 4 kg higher at 48 weeks (p = 0.0001) and abdominal circumference 3 cm larger at 24 weeks (p = 0.022). No forgetfulness occurred in 98.7% of patients. Patient satisfaction was 90/100 at 4, 24, and 48 weeks. Conclusion: Real-world data demonstrate that dolutegravir plus lamivudine in MTR is effective, safe, and satisfactory, moderately increasing weight and abdominal circumference and administrable on a test-and-treat strategy. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)
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6 pages, 216 KiB  
Communication
Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort
by Arturo Ciccullo, Gianmaria Baldin, Vanni Borghi, Filippo Lagi, Alessandra Latini, Gabriella d’Ettorre, Letizia Oreni, Paolo Fusco, Amedeo Capetti, Massimiliano Fabbiani, Andrea Giacomelli, Alessandro Grimaldi, Giordano Madeddu, Gaetana Sterrantino, Cristina Mussini and Simona Di Giambenedetto
Viruses 2022, 14(1), 163; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010163 - 17 Jan 2022
Cited by 5 | Viewed by 1711
Abstract
Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We [...] Read more.
Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)

Review

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13 pages, 705 KiB  
Review
Apples to Apples? A Comparison of Real-World Tolerability of Antiretrovirals in Patients with Human Immunodeficiency Virus Infection and Patients with Primary Biliary Cholangitis
by Shannon L. Turvey, Lynora Saxinger and Andrew L. Mason
Viruses 2022, 14(3), 516; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030516 - 03 Mar 2022
Cited by 3 | Viewed by 2354
Abstract
We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As [...] Read more.
We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As such, PBC patients have been treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), alone and in combination with a boosted protease inhibitor or an integrase strand transfer inhibitor in case studies and clinical trials. However, a randomized controlled trial using combination antiretroviral therapy with lopinavir was terminated early because 70% of PBC patients discontinued therapy because of gastrointestinal side effects. In the open-label extension, patients tolerating combination therapy underwent a significant reduction in serum liver parameters, whereas those on NRTIs alone rebounded to baseline. Herein, we compare clinical experience in the experimental use of antiretroviral agents in patients with PBC with the broader experience of using these agents in people living with HIV infection. While the incidence of gastrointestinal side effects in the PBC population appears somewhat increased compared to those with HIV infection, the clinical improvement observed in patients with PBC suggests that further studies using the newer and better tolerated antiretroviral agents are warranted. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)
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11 pages, 292 KiB  
Review
Impact of Combined Antiretroviral Therapy on Metabolic Syndrome Components in Adult People Living with HIV: A Literature Review
by Mariusz Sapuła, Magdalena Suchacz, Andrzej Załęski and Alicja Wiercińska-Drapało
Viruses 2022, 14(1), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010122 - 11 Jan 2022
Cited by 17 | Viewed by 2694
Abstract
The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980’s. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday [...] Read more.
The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980’s. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday clinical practice. With the life expectancy of people living with HIV rapidly approaching that of their HIV-negative counterparts, the influence of these antiretrovirals on the development of the components of the metabolic syndrome remains of major interest to clinicians and their patients. In this review, we aimed to discuss the impact of cART on components of the metabolic syndrome, i.e., weight, plasma lipid levels, plasma glucose levels, and blood pressure, describing the influence of cART classes and of individual antiretrovirals. We also aimed to outline the limitations of the research conducted to date and the remaining knowledge gaps in this area. Full article
(This article belongs to the Special Issue Adverse Effects of Antiretroviral Therapy)
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