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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 -
The Lancet. HIV Dec 2022Combination therapy with three antiretroviral agents has been integral to successful HIV-1 treatment since 1996. Although the efficacy, adverse effects, and toxicities... (Review)
Review
Combination therapy with three antiretroviral agents has been integral to successful HIV-1 treatment since 1996. Although the efficacy, adverse effects, and toxicities of contemporary three-drug regimens have improved, even the newest therapies have potential adverse effects. The use of two-drug regimens is one way to reduce lifetime exposure to antiretroviral drugs while maintaining the benefits of viral suppression. Multiple large, randomised trials have shown the virological non-inferiority of certain two-drug regimens versus three-drug comparators, including adverse effect differences that reflect known profiles of the antiretroviral drugs in the respective regimens. Two-drug combinations are now recommended in treatment guidelines and include the first long-acting antiretroviral regimen for the treatment of HIV-1. Recommended two-drug regimens differ in their risks for, and factors associated with, virological failure and emergent resistance. The tolerability, safety, metabolic profiles, and drug interactions of two-drug regimens also vary by the constituent drugs. No current two-drug regimen is recommended for people with chronic hepatitis B virus as none include tenofovir. Two-drug regimens have increased options for individualised care.
Topics: Humans; Anti-HIV Agents; HIV Infections; Hepatitis B, Chronic; HIV-1; Tenofovir; Anti-Retroviral Agents; Drug Therapy, Combination
PubMed: 36309038
DOI: 10.1016/S2352-3018(22)00249-1 -
The Lancet. HIV May 2023Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully... (Review)
Review
Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART.
Topics: Humans; Anti-HIV Agents; HIV Infections; Anti-Retroviral Agents; Rilpivirine; Injections, Intramuscular
PubMed: 37062293
DOI: 10.1016/S2352-3018(23)00051-6 -
Infectious Disease Clinics of North... Sep 2019Approximately 20% of people with HIV in the United States prescribed antiretroviral therapy are not virally suppressed. Thus, optimal management of virologic failure has... (Review)
Review
Approximately 20% of people with HIV in the United States prescribed antiretroviral therapy are not virally suppressed. Thus, optimal management of virologic failure has a critical role in the ability to improve viral suppression rates to improve long-term health outcomes for those infected and to achieve epidemic control. This article discusses the causes of virologic failure, the use of resistance testing to guide management after failure, interpretation and relevance of HIV drug resistance patterns, considerations for selection of second-line and salvage therapies, and management of virologic failure in special populations.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Disease Management; Drug Resistance, Viral; HIV; HIV Infections; Humans; Sustained Virologic Response; Treatment Failure; United States
PubMed: 31255384
DOI: 10.1016/j.idc.2019.05.004 -
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 -
Drugs Sep 2022Lenacapavir (Sunlenca) is a long-acting capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) being developed by Gilead Sciences Inc. It is available as an... (Review)
Review
Lenacapavir (Sunlenca) is a long-acting capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) being developed by Gilead Sciences Inc. It is available as an oral tablet and injectable solution, with the latter being a slow-release formulation to allow bi-annual subcutaneous administration. In August 2022, lenacapavir received its first approval in the EU for use in combination with other antiretroviral(s) in adults with multi-drug resistant HIV infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen. This article summarizes the milestones in the development of lenacapavir leading to this first approval for the treatment of HIV-1 infection.
Topics: Adult; Humans; HIV Infections; Anti-HIV Agents; HIV-1; Anti-Retroviral Agents
PubMed: 36272024
DOI: 10.1007/s40265-022-01786-0 -
Current Opinion in HIV and AIDS Jan 2017To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. (Review)
Review
PURPOSE OF REVIEW
To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk.
RECENT FINDINGS
HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk.
SUMMARY
The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Neoplasms; Risk Assessment
PubMed: 27755153
DOI: 10.1097/COH.0000000000000334 -
Molecules (Basel, Switzerland) Aug 2021When the first cases of HIV infection appeared in the 1980s, AIDS was a deadly disease without any therapeutic alternatives. Currently, there is still no cure for most... (Review)
Review
When the first cases of HIV infection appeared in the 1980s, AIDS was a deadly disease without any therapeutic alternatives. Currently, there is still no cure for most cases mainly due to the multiple tissues that act as a reservoir for this virus besides the high viral mutagenesis that leads to an antiretroviral drug resistance. Throughout the years, multiple drugs with specific mechanisms of action on distinct targets have been approved. In this review, the most recent phase III clinical studies and other research therapies as advanced antiretroviral nanodelivery systems will be here discussed. Although the combined antiretroviral therapy is effective in reducing viral loading to undetectable levels, it also presents some disadvantages, such as usual side effects, high frequency of administration, and the possibility of drug resistance. Therefore, several new drugs, delivery systems, and vaccines have been tested in pre-clinical and clinical trials. Regarding drug delivery, an attempt to change the route of administration of some conventional antiretrovirals has proven to be successful and surpassed some issues related to patient compliance. Nanotechnology has brought a new approach to overcoming certain obstacles of formulation design including drug solubility and biodistribution. Overall, the encapsulation of antiretroviral drugs into nanosystems has shown improved drug release and pharmacokinetic profile.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; HIV Infections; Humans
PubMed: 34500737
DOI: 10.3390/molecules26175305 -
South African Medical Journal =... Aug 2022
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; HIV Infections; Humans; South Africa; Treatment Outcome; Viral Load
PubMed: 36214399
DOI: 10.7196/SAMJ.2022.v112i8.16695 -
Cells Apr 2021Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are... (Review)
Review
Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.
Topics: Animals; Anti-Retroviral Agents; Autophagy; Drug Therapy, Combination; HIV; Humans; Protease Inhibitors; Reverse Transcriptase Inhibitors
PubMed: 33920955
DOI: 10.3390/cells10040909