-
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 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 -
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 -
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 -
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 -
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 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 -
Ugeskrift For Laeger Jul 2018HIV guidelines recommend assessment of conception issues for all people living with HIV. Studies have shown negligible risk of HIV transmission from well-treated... (Review)
Review
HIV guidelines recommend assessment of conception issues for all people living with HIV. Studies have shown negligible risk of HIV transmission from well-treated patients with HIV, and therefore condoms are no longer recom-mended to reduce HIV transmission. Some antiretroviral agents are metabolised through the same enzyme systems in the liver as hormonal contraceptives, which can affect the plasma concentration of both drug classes and the effect of the drugs, including reduced contraceptive efficacy. This review discusses the interactions between antiretroviral agents and hormonal contraceptives.
Topics: Anti-Retroviral Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Cytochrome P-450 Enzyme System; Drug Interactions; Female; HIV Infections; Humans; Intrauterine Devices, Medicated; Pregnancy
PubMed: 30037382
DOI: No ID Found -
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 -
South African Medical Journal =... Aug 2022In 2021, South Africa (SA) had an estimated 7.8 million people living with HIV, of whom 5.6 million were receiving antiretroviral therapy (ART),[1] with 3.4 million on...
In 2021, South Africa (SA) had an estimated 7.8 million people living with HIV, of whom 5.6 million were receiving antiretroviral therapy (ART),[1] with 3.4 million on first-line ART, 145 000 on second-line ART (SLART) and >700 on third-line ART (TLART).
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; South Africa; Viral Load
PubMed: 36214397
DOI: No ID Found