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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 -
Stem Cell Reviews and Reports Apr 2022The introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic,... (Review)
Review
The introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic, well-managed disease. However, these therapies do not eliminate all infected cells from the body despite suppressing viral load. Viral rebound is largely due to the presence of cellular reservoirs which support long-term persistence of HIV-1. A thorough understanding of the HIV-1 reservoir will facilitate the development of new strategies leading to its detection, reduction, and elimination, ultimately leading to curative therapies for HIV-1. Although immune cells derived from lymphoid and myeloid progenitors have been thoroughly studied as HIV-1 reservoirs, few studies have examined whether mesenchymal stromal/stem cells (MSCs) can assume this function. In this review, we evaluate published studies which have assessed whether MSCs contribute to the HIV-1 reservoir. MSCs have been found to express the receptors and co-receptors required for HIV-1 entry, albeit at levels of expression and receptor localisation that vary considerably between studies. Exposure to HIV-1 and HIV-1 proteins alters MSC properties in vitro, including their proliferation capacity and differentiation potential. However, in vitro and in vivo experiments investigating whether MSCs can become infected with and harbour latent integrated proviral DNA are lacking. In conclusion, MSCs appear to have the potential to contribute to the HIV-1 reservoir. However, further studies are needed using techniques such as those used to prove that cluster of differentiation (CD)4 T cells constitute an HIV-1 reservoir before a reservoir function can definitively be ascribed to MSCs. MSCs may contribute to HIV-1 persistence in vivo in the vasculature, adipose tissue, and bone marrow by being a reservoir for latent HIV-1. To harbour latent HIV-1, MSCs must express HIV-1 entry markers, and show evidence of productive or latent HIV-1 infection. The effect of HIV-1 or HIV-1 proteins on MSC properties may also be indicative of HIV-1 infection.
Topics: Animals; Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Macaca mulatta; Mesenchymal Stem Cells; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Virus Latency
PubMed: 34973144
DOI: 10.1007/s12015-021-10298-5 -
AIDS (London, England) Nov 2014
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Congenital Abnormalities; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy
PubMed: 25493603
DOI: 10.1097/QAD.0000000000000500 -
Scientific Reports Oct 2023'Kick and kill' cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill)....
'Kick and kill' cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill). In the Research in Viral Eradication of HIV Reservoirs trial (NCT02336074), people diagnosed with primary HIV infection received immediate antiretroviral therapy (ART) and were randomised 24 weeks later to either a latency-reversing agent, vorinostat, together with ChAdV63.HIVconsv and MVA.HIVconsv vaccines, or ART alone. This intervention conferred no reduction in HIV-1 reservoir size over ART alone, despite boosting virus-specific CD4+ and CD8+ T cells. The effects of the intervention were examined at the cellular level in the two trial arms using unbiased computational analysis of polyfunctional scores. This showed that the frequency and polyfunctionality of virus-specific CD4+ and CD8+ T cell populations were significantly increased over 12 weeks post-vaccination, compared to the ART-only arm. HIV-specific IL-2-secreting CD8+ T cells also expanded significantly in the intervention arm and were correlated with antiviral activity against heterologous HIV in vitro. Therapeutic vaccination during ART commenced in primary infection can induce functional T cell responses that are phenotypically similar to those of HIV controllers. Analytical therapy interruption may help determine their ability to control HIV in vivo.
Topics: Humans; HIV Infections; HIV-1; Anti-Retroviral Agents; HIV Seropositivity; CD8-Positive T-Lymphocytes; Vaccination; CD4-Positive T-Lymphocytes; Virus Latency
PubMed: 37821472
DOI: 10.1038/s41598-023-42888-3 -
AIDS Care Aug 2022The aim of this study was to determine the effect of lipodystrophy on self-esteem and adherence to antiretroviral therapy (ART) in people living with HIV (PLHIV). A...
The aim of this study was to determine the effect of lipodystrophy on self-esteem and adherence to antiretroviral therapy (ART) in people living with HIV (PLHIV). A cross-sectional and comparative study was carried out in an infection clinic, with 125 patients with lipodystrophy and 125 without lipodystrophy. Sociodemographic, clinical and epidemiological data were collected, using the Rosenberg Self-Esteem Scale and Assessment of Adherence to Antiretroviral Treatment Questionnaire (CEAT-VIH). Descriptive statistics and univariate and multivariate logistic regression analysis were used. Of the total sample, 57.2% had unsatisfactory self-esteem and 57.6% adequate adherence to ART. Self-esteem was lower in PLHIV with lipodystrophy (66.4%). PLHIV with monthly income less than or equal to two minimum wages ( < 0.001) and those with lipodystrophy had more unsatisfactory self-esteem ( < 0.001). Catholics had better self-esteem ( = 0.012), when compared to those without religion. Patients with monthly income less than or equal to two minimum wages ( = 0.021) and people with unsatisfactory self-esteem had more inadequate adherence to ART ( = 0.001). Catholics had better adherence to antiretrovirals ( = 0.007). In conclusion, lipodystrophy and low income negatively affect the self-esteem of PLHIV. Low income and unsatisfactory self-esteem make adherence to ART difficult. Religion is a protective factor for satisfactory self-esteem and adherence to antiretrovirals.
Topics: Anti-Retroviral Agents; Cross-Sectional Studies; HIV Infections; Humans; Lipodystrophy; Medication Adherence; Self Concept
PubMed: 34082636
DOI: 10.1080/09540121.2021.1936442 -
Current Opinion in HIV and AIDS Mar 2020To highlight recent data on antiretroviral adherence in older people living with HIV (PLWH), describe the most relevant pharmacokinetic antiretroviral studies, and... (Review)
Review
PURPOSE OF REVIEW
To highlight recent data on antiretroviral adherence in older people living with HIV (PLWH), describe the most relevant pharmacokinetic antiretroviral studies, and identify critical research gaps in this population.
RECENT FINDINGS
Overall, studies have found that older PLWH are more likely to be adherent to antiretroviral therapy (ART). Although multiple methods to measure adherence are available (self-report, pharmacy refills, electronic device monitors, drug concentrations), there is currently no 'gold standard' adherence measure or sufficient evidence to suggest a preferred method in older patients. Recently, studies evaluating antiretroviral concentrations in hair and dried blood spots in older patients identified no major differences when compared with younger individuals. Similarly, although pharmacokinetic studies in older PLWH are scarce, most data reveal no significant pharmacokinetic differences in the aging population. Furthermore, no specific guidelines or treatment recommendations regarding ART dose modification or long-term toxicity in aging PLWH are available, mostly because of the exclusion of this population in clinical trials.
SUMMARY
How aging influences adherence and pharmacokinetics remains poorly understood. As the population of older PLWH increases, research focusing on adherence, toxicity, drug--drug interactions, and the influence of comorbidities is needed.
Topics: Adult; Aged; Aged, 80 and over; Aging; Anti-HIV Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Comorbidity; Drug Interactions; Frailty; HIV Infections; Humans; Medication Adherence
PubMed: 31977338
DOI: 10.1097/COH.0000000000000615 -
Clinical Pharmacokinetics Apr 2017Antiretroviral treatment is highly effective in enhancing HIV-positive patients' survival and quality of life. Despite an increased tolerability in recent years, a... (Review)
Review
BACKGROUND
Antiretroviral treatment is highly effective in enhancing HIV-positive patients' survival and quality of life. Despite an increased tolerability in recent years, a substantial amount of patients experience side effects. Antiretrovirals' efficacy and tolerability have been associated with plasma concentrations and single nucleotide polymorphisms in selected genes involved in drug disposition.
OBJECTIVE
Our aim was to review the current knowledge in genetic polymorphisms affecting plasma, intracellular or compartmental concentrations of antiretrovirals.
METHODS
A search of the PubMed database was conducted to identify relevant articles, using the following terms: 'pharmacogenetics' or 'pharmacogenomics' or 'single nucleotide polymorphisms' or 'genetic/allelic variants' and 'pharmacokinetics' or 'concentrations' and 'HIV' or 'antiretroviral'. Abstracts from the main HIV conferences during 2015 and 2016 were also searched using the same keywords. Abstracts were manually checked and, if relevant, full papers were obtained. Only articles published in English were selected.
RESULTS
Several genetic polymorphisms in genes coding enzymes involved in drug metabolism (cytochrome P450 isoenzymes and uridine diphosphate glucuronosyltransferases) and transport (P-glycoprotein, anionic and cationic transporters, other transporters), as well as nuclear receptors (pregnane X receptor and the constitutive androstane receptor), have been associated with concentrations of antiretrovirals. The extent of such influence, the conflicting data, and the potential clinical relevance are discussed in the main section of this article.
CONCLUSION
Genetic polymorphisms may affect antiretroviral disposition, as well as both efficacy and toxicity. Despite a large amount of data, such precious knowledge has seldom been applied in patients. Studies on the clinical relevance and cost effectiveness of tailoring antiretroviral regimens to patients' genetic assets are lacking, but their importance may grow with the increasing age and complexity of persons living with HIV/AIDS.
Topics: Animals; Anti-HIV Agents; Anti-Retroviral Agents; Drug Interactions; HIV Infections; Humans; Polymorphism, Genetic; Tissue Distribution
PubMed: 27641153
DOI: 10.1007/s40262-016-0456-6 -
Current Opinion in HIV and AIDS Mar 2015To summarize current knowledge and provide perspective on relationships between human genetic variants, antiretroviral medications, and aging-related complications of... (Review)
Review
PURPOSE OF REVIEW
To summarize current knowledge and provide perspective on relationships between human genetic variants, antiretroviral medications, and aging-related complications of HIV-1 infection.
RECENT FINDINGS
Human genetic variants have been convincingly associated with interindividual variability in antiretroviral toxicities, drug disposition, and aging-associated complications in HIV-1 infection. Screening for HLA-B5701 to avoid abacavir hypersensitivity reactions has become a routine part of clinical care, and has markedly improved drug safety. There are well established pharmacogenetic associations with other agents (efavirenz, nevirapine, atazanavir, dolutegravir, and others), but this knowledge has yet to have substantial impact on HIV-1 clinical care. As metabolic complications including diabetes mellitus, dyslipidemia, osteoporosis, and cardiovascular disease are becoming an increasing concern among individuals who are aging with well controlled HIV-1 infection, human genetic variants that predispose to these complications also become more relevant in this population.
SUMMARY
Pharmacogenetic knowledge has already had considerable impact on antiretroviral prescribing. With continued advances in the field of human genomics, the impact of pharmacogenomics on HIV-1 clinical care and research is likely to continue to grow in importance and scope.
Topics: Anti-Retroviral Agents; Comorbidity; HIV Infections; Humans; Pharmacogenetics
PubMed: 25565175
DOI: 10.1097/COH.0000000000000134 -
Sante Publique (Vandoeuvre-les-Nancy,... Jun 2020This article presents the results of a qualitative research on practices of dispensing antiretroviral medication concerning requests for greater than one month, for...
This article presents the results of a qualitative research on practices of dispensing antiretroviral medication concerning requests for greater than one month, for departure abroad. In spite of a strict regulation, a cartography shows a heterogeneity of its application leading to a great diversity of dispensing practices. This qualitative research with 22 pharmacies across the territory reveals relational and regulatory logics that contribute to this non-uniformity of practices. The concepts of embarrassment, professional commitment, regulatory concerns and personal relationships with patients largely explain the accommodations and crafts observed in this type of ARV dispensing request.
Topics: Anti-Retroviral Agents; Drug Prescriptions; France; Humans; Legislation, Drug; Pharmacies; Qualitative Research; Travel
PubMed: 32706231
DOI: 10.3917/spub.201.0097 -
Topics in Antiviral MedicineAntiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START... (Review)
Review
Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Monitoring; HIV Infections; Humans; Time Factors
PubMed: 27398769
DOI: No ID Found