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Trends in Pharmacological Sciences Jan 2022Since the first cases of AIDS appeared in 1981, human immunodeficiency virus type 1 (HIV-1) infection has reached pandemic proportions. Forty years later, research has... (Review)
Review
Since the first cases of AIDS appeared in 1981, human immunodeficiency virus type 1 (HIV-1) infection has reached pandemic proportions. Forty years later, research has led to the approval of more than 30 antiretroviral drugs, while combination therapies have turned HIV-1 infection into a chronic, but manageable disease. Still, drug toxicity and acquired and transmitted drug resistance remain as major threats to therapy success. In this review, we provide an overview on currently available anti-HIV drugs and the latest developments in antiretroviral therapy, focused on new antiretroviral agents acting on known and unexploited antiviral targets, prevention therapies aimed to improve available drug combinations, and research on new long-acting therapies, particularly those involving novel drug candidates such as lenacapavir or islatravir.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; HIV Infections; Humans
PubMed: 34742581
DOI: 10.1016/j.tips.2021.10.004 -
Infectious Disease Clinics of North... Sep 2014The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic... (Review)
Review
The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Discovery; HIV Infections; History, 20th Century; History, 21st Century; Humans
PubMed: 25151562
DOI: 10.1016/j.idc.2014.06.001 -
HIV Medicine Mar 2019Initiating antiretroviral therapy (ART) as early as the day of HIV diagnosis is a strategy of increasing global interest to control the HIV epidemic and optimize the... (Review)
Review
Initiating antiretroviral therapy (ART) as early as the day of HIV diagnosis is a strategy of increasing global interest to control the HIV epidemic and optimize the health of people living with HIV (PLWH). No detrimental effects of rapid-start ART have been identified in randomized controlled trials undertaken in low- or middle-income countries, or in cohort studies performed in high-income countries. Rapid-start ART may be a key approach in reaching the 2020 Joint United Nations Programme on HIV/AIDS goal of 90% of all PLWH knowing their status, 90% of those diagnosed receiving sustained ART, and 90% of those receiving ART achieving viral suppression; it may also be important for achieving the suggested fourth "90%" goal: improving health-related quality-of-life in PLWH. Presently there is insufficient broad evidence for guidelines to recommend universal test-and-treat strategies for all people, in all settings, at HIV diagnosis; consequently, there is a pressing need to conduct high-quality studies that investigate immediate ART initiation. This article evaluates global evidence regarding rapid-start ART, including same-day start, with particular focus on the implementation of this strategy in high-income countries.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Disease Management; Drug-Related Side Effects and Adverse Reactions; Global Health; HIV Infections; Humans; Secondary Prevention; Treatment Outcome
PubMed: 30724450
DOI: 10.1111/hiv.12708 -
Current Opinion in HIV and AIDS Nov 2021HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors... (Review)
Review
PURPOSE OF REVIEW
HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART.
RECENT FINDINGS
Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern.
SUMMARY
CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.
Topics: Anti-Retroviral Agents; HIV Infections; Humans; Protease Inhibitors
PubMed: 34545036
DOI: 10.1097/COH.0000000000000702 -
Infectious Disease Clinics of North... Sep 2019With the second-generation integrase inhibitors (dolutegravir and bictegravir) extending the attributes of earlier integrase inhibitors, three-drug regimens containing... (Review)
Review
With the second-generation integrase inhibitors (dolutegravir and bictegravir) extending the attributes of earlier integrase inhibitors, three-drug regimens containing integrase inhibitors plus two nucleos(t)ide reverse transcriptase inhibitors are now widely recommended for first-line (initial) treatment of human immunodeficiency virus-1 infection. Led by dolutegravir plus lamivudine, two-drug therapy is emerging as a way to reduce antiretroviral therapy cost and adverse effects without compromising treatment options should virologic failure occur. Initial two-drug therapy has limitations, including the relative incompatibility with the coemerging concept of same-day antiretroviral therapy initiation.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Treatment Outcome
PubMed: 31239093
DOI: 10.1016/j.idc.2019.05.003 -
Journal of the Mississippi State... Jun 2015
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Monitoring; Drug Resistance, Viral; HIV Infections; Humans; Medication Adherence; Treatment Outcome
PubMed: 26242056
DOI: No ID Found -
Infectious Disease Clinics of North... Sep 2019This review provides a synopsis of key clinical considerations for switching antiretroviral therapy (ART) for individuals with human immunodeficiency virus who have... (Review)
Review
This review provides a synopsis of key clinical considerations for switching antiretroviral therapy (ART) for individuals with human immunodeficiency virus who have maintained a routinely suppressed viral load. There may be benefits but also risks involved in every ART regimen change, so strategies for prioritizing individuals for a switch based on the specific antiretroviral agents in the regimen are discussed, along with approaches to ensure maintenance of viral suppression after treatment modifications. Controversial and evolving questions in the area of ART switches and simplifications are also considered.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Substitution; HIV Infections; Humans; Sustained Virologic Response
PubMed: 31255385
DOI: 10.1016/j.idc.2019.04.003 -
Journal of Virology Jun 2010Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely... (Review)
Review
Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338:853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not obscure the magnitude of the ongoing worldwide HIV epidemic (R. P. Walensky, A. D. Paltiel, E. Losina, L. M. Mercincavage, B. R. Schackman, P. E. Sax, M. C. Weinstein, and K. A. Freedberg, J. Infect. Dis. 194:11-19, 2006). Readers of the Journal of Virology are doubtless aware of the fundamental advances in retrovirology that have made possible the development of potent inhibitors of HIV replication. In this review, we focus on the issues surrounding how these drugs and drug regimens are actually used in clinical settings. Their proper use requires detailed knowledge of the natural history of HIV infection, the pharmacology of the individual drugs, the complexities of drug-drug interactions, and the use of sophisticated molecular tests for monitoring of viral load, immunologic response, and drug resistance.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Humans
PubMed: 20181709
DOI: 10.1128/JVI.02524-09 -
Topics in Antiviral Medicine 2014Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in the HIV-infected population than in the general population. AKI is associated with an... (Review)
Review
Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in the HIV-infected population than in the general population. AKI is associated with an increased risk of heart failure, cardiovascular disease, end-stage renal disease (ESRD), and mortality. Tenofovir is associated with severe AKI in a small percentage of patients and with subclinical abnormalities in many more. HIV-associated nephropathy is now a relatively rare form of CKD, because of the widespread use of potent antiretroviral therapy. The CKD spectrum in HIV-infected patients has become more frequently characterized by comorbid CKD, with an increased frequency of CKD related to diabetes or hypertension being observed. Kidney transplantation is a therapeutic option for HIV-infected patients with ESRD if their HIV infection is controlled, although rates of acute graft rejection and drug-drug interactions are high. This article summarizes a presentation by Christina M. Wyatt, MD, at the IAS-USA continuing education program held in Washington, DC, in June 2013.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Histocytochemistry; Humans; Kidney; Kidney Diseases; Middle Aged
PubMed: 25101531
DOI: No ID Found -
Antiviral Therapy Oct 2023Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon... (Review)
Review
Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.
Topics: Humans; Anti-Retroviral Agents; Mutation
PubMed: 37749751
DOI: 10.1177/13596535231201162