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Infectious Disease Clinics of North... Sep 2019Antiretroviral therapy has advanced significantly since zidovudine was first approved. Although 31 antiretrovirals have been approved by the FDA, only about half of... (Review)
Review
Antiretroviral therapy has advanced significantly since zidovudine was first approved. Although 31 antiretrovirals have been approved by the FDA, only about half of those are commonly used. Newer, more tolerable agents have made human immunodeficiency virus into a chronic condition, which can be managed with medication. The most common antiretroviral regimens consist of 2 nucleoside reverse transcriptase inhibitors plus a third agent, often an integrase inhibitor because of better tolerability and fewer drug interactions than other regimens. Understanding the dosage forms, adverse effects, and drug interactions of antiretrovirals allow clinicians to choose the most appropriate regimen for their patient. New developments, such as branded generic regimens and long-acting intramuscular injections, may play a larger role in the future.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans
PubMed: 31395145
DOI: 10.1016/j.idc.2019.05.006 -
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 -
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 -
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 -
Der Internist Apr 2019Human immunodeficiency virus (HIV) infection has become a chronic disease with a favourable prognosis if adequate antiretroviral therapy (ART) is applied. Therefore,... (Review)
Review
Human immunodeficiency virus (HIV) infection has become a chronic disease with a favourable prognosis if adequate antiretroviral therapy (ART) is applied. Therefore, each patient with HIV infection should be treated irrespectively of clinical symptoms or of immunological status. A combination of three active drugs that have to be taken life-long has been standard for many years. The regimen contains two nucleoside reverse transcriptase inhibitors plus either an integrase inhibitor, a boosted protease inhibitor, or a non-nucleoside reverse transcriptase inhibitor. Integrase inhibitors are recommended as the third partner of choice by recent guidelines due to their high efficacy and their favourable safety profile. Many combination drugs are now available which allow a simple treatment with few tablets and in many instances a one-pill combination per day is an option. Potential interactions with drugs given for other diseases have to be taken into account, especially if a pharmacological booster is part of the regimen. Combination therapy should be changed if either virological failure (HIV RNA >200 copies/ml) or drug-related adverse events occur. In special situations (e. g. pregnancy) highly experienced experts in the field should be consulted. Novel approaches for HIV therapy include dual therapy as well as treatment with long-acting substances. Beside therapy, antiretroviral drugs are used for prevention either as post-exposure prophylaxis or as pre-exposure prophylaxis.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Drug Therapy, Combination; Female; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Pregnancy; Protease Inhibitors; Reverse Transcriptase Inhibitors; Viral Load
PubMed: 30778612
DOI: 10.1007/s00108-019-0564-0 -
Internal Medicine Journal Apr 2022The past four decades have seen enormous progress in the diagnosis and management of human immunodeficiency virus (HIV) infection. There have been significant advances...
The past four decades have seen enormous progress in the diagnosis and management of human immunodeficiency virus (HIV) infection. There have been significant advances spanning the approval of the first antiretroviral agents, the advent of combination antiretroviral therapy to single tablet regimens with minimal toxicity. Although these remarkable developments have on the surface led to the 'end of AIDS', there are still key populations being left behind. This clinical update will describe the diagnosis and management of HIV, and the changing paradigms that have seen HIV transform from a life-limiting condition to a manageable chronic disease over a few decades.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Chronic Disease; HIV Infections; Humans
PubMed: 35419962
DOI: 10.1111/imj.15739 -
AIDS Patient Care and STDs Mar 2022In the era of widespread use of antiretroviral therapy (ART), people with HIV (PWH) have a near-normal life expectancy. However, PWH have high rates of kidney diseases... (Review)
Review
In the era of widespread use of antiretroviral therapy (ART), people with HIV (PWH) have a near-normal life expectancy. However, PWH have high rates of kidney diseases and progression to end-stage renal disease at a younger age. PWH have multiple risks for developing acute and chronic kidney diseases, including traditional risk factors such as diabetes, hypertension, and HIV-related factors such as HIV-associated nephropathy and increased susceptibility to infections and exposure to nephrotoxic medications. Despite an improvement in access to kidney transplant among PWH, the number of PWH on dialysis continues to increase. The expansion of the number of antiretrovirals (ARVs) and kidney replacement modalities, the absence of pharmacokinetic data, and therapeutic drug monitoring make it very challenging for providers to dose ARVs appropriately leading to medication errors, adverse events, and higher mortality. Most of the recommendations are either based on small sample size studies or extrapolated based on physiochemical characteristics of ART. We aim to review the most available and most current literature on ART in PWH with renal insufficiency and ART dosing recommendations on dialysis to ensure that PWH are provided with the safest and most effective ART regimen.
Topics: Anti-Retroviral Agents; Female; HIV Infections; Humans; Kidney Transplantation; Male; Renal Dialysis; Renal Insufficiency
PubMed: 35289690
DOI: 10.1089/apc.2021.0173 -
Current HIV/AIDS Reports Apr 2017Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence... (Review)
Review
PURPOSE OF REVIEW
Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals.
RECENT FINDINGS
Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Delayed-Action Preparations; Drug Discovery; Female; HIV Infections; Humans; Rilpivirine
PubMed: 28303548
DOI: 10.1007/s11904-017-0353-0 -
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 -
Health Affairs (Project Hope) Sep 2019
Topics: Anti-Retroviral Agents; Cost of Illness; Health Services Accessibility; Humans
PubMed: 31479359
DOI: 10.1377/hlthaff.2019.01020