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Molecules (Basel, Switzerland) Sep 2019In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body... (Review)
Review
In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Aquatic Organisms; Biological Products; Drug Development; Fish Oils; HIV-1; Humans; Structure-Activity Relationship
PubMed: 31561445
DOI: 10.3390/molecules24193486 -
Current Opinion in HIV and AIDS Jul 2022To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational... (Review)
Review
PURPOSE OF REVIEW
To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs).
RECENT FINDINGS
The greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy.
SUMMARY
PrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Broadly Neutralizing Antibodies; Drug Resistance; Emtricitabine; HIV Infections; HIV-1; Humans; Pre-Exposure Prophylaxis; Tenofovir
PubMed: 35762376
DOI: 10.1097/COH.0000000000000746 -
Continuum (Minneapolis, Minn.) Dec 2015Neurologic complications of human immunodeficiency virus (HIV) infection remain common, despite effective antiretroviral treatment (ART). Neurologic manifestations may... (Review)
Review
PURPOSE OF REVIEW
Neurologic complications of human immunodeficiency virus (HIV) infection remain common, despite effective antiretroviral treatment (ART). Neurologic manifestations may be due to opportunistic infection, immune reconstitution, or the virus itself, posing diagnostic challenges for the neurologist. Neurologists are also asked to comment on the use of immunomodulatory agents in these patients and to manage long-term complications, such as neurocognitive disorders and peripheral neuropathy or the associated comorbidities.
RECENT FINDINGS
HIV enters the central nervous system (CNS) soon after infection and can cause atrophy of the brain within 3 months of infection. As patients are living longer, comorbidities such as stroke associated with metabolic syndrome, hepatitis C, and drug abuse are important contributory factors to the neurologic and neuropsychiatric manifestations of HIV infection. Immune-mediated syndromes are increasingly being recognized in patients with HIV infection on antiretroviral therapy. This includes a subacute T-cell-mediated encephalitis called CNS-immune reconstitution inflammatory syndrome, fulminant multiple sclerosis-like lesions, and unmasking of underlying opportunistic infections with profound inflammatory reaction. Our understanding of the most appropriate antiretrovirals for treating or preventing CNS HIV replication continues to improve. Major efforts are being made to understand how the CNS reservoirs are established and maintained, and new approaches are being developed to develop a functional cure or eradicate the virus.
SUMMARY
This article reviews the neurologic complications caused by HIV infection, associated comorbidities, or antiretroviral drugs that are commonly encountered by neurologists.
Topics: Anti-Retroviral Agents; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Nervous System Diseases
PubMed: 26633776
DOI: 10.1212/CON.0000000000000244 -
The Journal of the Association of... 2019Scale-up of antiretroviral therapy (ART) for people living with HIV requires differentiated models of ART delivery to improve access and contribute to achieving viral...
Scale-up of antiretroviral therapy (ART) for people living with HIV requires differentiated models of ART delivery to improve access and contribute to achieving viral suppression for 95% of people on ART. We examined barriers and enablers in South Africa via semistructured interviews with 33 respondents (program implementers, nurses, and other health care providers) from 11 organizations. The interviews were recorded, transcribed, and analyzed for emerging themes using NVivo 11 software. Major enablers of ART delivery included model flexibility, provision of standardized guidance, and an increased focus on person-centered care. Major barriers were related to financial, human, and space resources and the need for time to allow buy-in. Stigma emerged as both a barrier and an enabler. Findings suggest that creating and strengthening models that cater to client needs can achieve better health outcomes. South Africa's efforts can inform emerging models in other settings to achieve epidemic control.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Attitude of Health Personnel; Community Health Services; Community-Based Participatory Research; Female; Focus Groups; HIV Infections; Health Personnel; Health Services Accessibility; Humans; Interviews as Topic; Medication Adherence; Patient Care Team; Patient-Centered Care; Qualitative Research; Social Stigma; South Africa
PubMed: 30720561
DOI: 10.1097/JNC.0000000000000062 -
Expert Review of Anti-infective Therapy Dec 2016Antiretroviral therapy is extremely effective in both children and adults infected with HIV. Treatment indications have rapidly expanded; ideally, with rare exceptions,... (Review)
Review
Antiretroviral therapy is extremely effective in both children and adults infected with HIV. Treatment indications have rapidly expanded; ideally, with rare exceptions, all infected children should now be treated. Areas covered: The use of antiretroviral drugs in children is based largely on extrapolations from experience with adult patients. Pharmacokinetic studies are required in addition to formal studies, which are difficult to conduct in pediatric situations, extending from birth to adolescence. However, despite often inadequate galenic formulation, treatment of children is easier than generally thought. No major or irreversible toxicity has been observed with the latest generation of molecules. Several observations suggest that very early treatment, beginning shortly after birth, provides better long-term immunological control of infection. Expert commentary: All HIV-infected children should be treated with antiretroviral drugs. Manufacturers should propose appropriate dosage forms, including combined forms in particular, and should support pharmacological and tolerance studies in pediatric patients of various ages. Very early treatment maximizes the chances of long-term immunological control.
Topics: Adolescent; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Child; Disease-Free Survival; HIV Infections; Humans; Infant, Newborn; Kaplan-Meier Estimate; Practice Guidelines as Topic
PubMed: 27645375
DOI: 10.1080/14787210.2016.1236686 -
Current Drug Metabolism 2015For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from... (Review)
Review
For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).
Topics: Animals; Anti-Retroviral Agents; Citrus paradisi; Garlic; Ginkgo biloba; Herb-Drug Interactions; Humans; Hypericum; Panax; Plants, Medicinal
PubMed: 26526838
DOI: 10.2174/1389200216666151103115053 -
The Lancet. HIV May 2019The evaluation of immune-based approaches to achieve an antiretroviral therapy free remission of HIV infection requires proven efficacy through antiretroviral therapy... (Review)
Review
The evaluation of immune-based approaches to achieve an antiretroviral therapy free remission of HIV infection requires proven efficacy through antiretroviral therapy interruption placebo-controlled trials. This approach is not without risk to participants and innovative trial designs need to be developed that minimise the number of participants treated with placebo and ineffective candidates. Multi-arm, multi-stage (MAMS) trial designs can be used in this context to accelerate the development of an immune-based therapeutic agent for HIV cure. Issues related to implementing a MAMS design within the planned EHVA T01 trial are considered here. EHVA T01 is a multicentre, MAMS, double-blind, phase 1 and 2 trial that aims to evaluate the effect of immune interventions on viral control in HIV-1 infected participants following analytic treatment interruption. The application of a MAMS design increases the likelihood that the EHVA T01 trial will identify a successful treatment and minimises the number of participants undergoing analytical treatment interruptions who have been treated with futile agents. The use of a MAMS design is a promising strategy to evaluate complex immune-based approaches aimed at curing HIV-infection, particularly relevant to the pipeline with multiple agents requiring examination.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; HIV Infections; HIV-1; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 31047670
DOI: 10.1016/S2352-3018(19)30082-7 -
Journal of Clinical Virology : the... Jan 2022The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the... (Review)
Review
The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; HIV; HIV Infections; Humans; Rilpivirine
PubMed: 34883407
DOI: 10.1016/j.jcv.2021.105032 -
Current Pharmaceutical Design 2017Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds... (Review)
Review
Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds are currently available, raltegravir, elvitegravir, dolutegravir and two more under development, bictegravir and cabotegravir. These compounds share the same mode of action but exhibit different pharmacokinetic/ pharmacodynamic properties, and drug-drug interactions. A series of studies in the past decade have established their efficacy compared to previous regimens, both in treatment- naïve and experienced patients. INSTIs have demonstrated a favorable safety profile with fewer adverse events and low rates of virological failure. Emergence of resistance to these agents, however, is a worrying concern, particularly for elvitegravir and raltegravir that display a lower genetic barrier than dolutegravir. On-going trials aim at establishing INSTIs as part of dual-drug HIV treatments or even monotherapy. New long-acting, injectable formulations are under investigation for treatment or prevention.
Topics: Anti-Retroviral Agents; Delayed-Action Preparations; Drug Compounding; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Raltegravir Potassium
PubMed: 28356041
DOI: 10.2174/1381612823666170329142059 -
Clinical Pharmacokinetics May 2022Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV,... (Review)
Review
Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids. These alterations may affect many aspects of antiretroviral pharmacokinetics. Some drug characteristics may result in subtherapeutic exposure and the potential related risk of treatment failure and resistance. Antiretrovirals that require low pH, administration of fatty meals, longer intestinal exposure, and an enterohepatic recirculation for their absorption may be most impacted by bariatric surgery procedures. Additionally, some antiretrovirals can interact with the polyvalent cations in supplements or drugs inhibiting gastric acid, thereby preventing their use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on the basis of drug characteristics solely proved to be challenging, therefore pharmacokinetic studies remain crucial in this population. Here, we discuss general implications of bariatric surgery on antiretroviral outcomes in people living with HIV as well as drug properties that are relevant for the choice of antiretroviral treatment in this special patient population. Additionally, we summarise studies that evaluated the pharmacokinetics of antiretrovirals post-bariatric surgery. Finally, we performed a comprehensive analysis of theoretical considerations and published pharmacokinetic and pharmacodynamic data to provide recommendations on antiretrovirals for people living with HIV undergoing bariatric surgery.
Topics: Anti-Retroviral Agents; Bariatric Surgery; HIV Infections; Humans; Obesity; Pharmaceutical Preparations
PubMed: 35404470
DOI: 10.1007/s40262-022-01120-7