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Journal of the International AIDS... Jun 2013Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV-infected adolescents globally. Their survival into adolescence and beyond represent... (Review)
Review
Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV-infected adolescents globally. Their survival into adolescence and beyond represent one of the major successes in the battle against the disease that has claimed the lives of millions of children. This population is diverse and there are unique issues related to antiretroviral treatment and management. Drawing from the literature and experience, this paper discusses several broad areas related to antiretroviral management, including: 1) diverse presentation of HIV, (2) use of combination antiretroviral therapy including in the setting of co-morbidities and rapid growth and development, (3) challenges of cART, including nonadherence, resistance, and management of the highly treatment-experienced adolescent patient, (4) additional unique concerns and management issues related to PHIV-infected adolescents, including the consequences of longterm inflammation, risk of transmission, and transitions to adult care. In each section, the experience in both resource-rich and limited settings are discussed with the aim of highlighting the differences and importantly the similarities, to share lessons learnt and provide insight into the multi-faceted approaches that may be needed to address the challenges faced by this unique and resilient population.
Topics: Adolescent; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; HIV Infections; Humans; Medication Adherence; Treatment Outcome
PubMed: 23782477
DOI: 10.7448/IAS.16.1.18579 -
Current Opinion in HIV and AIDS Jan 2014Recent WHO guidelines recommend immediate initiation of lifelong antiretroviral therapy (ART) in all children below 5 years, irrespective of immune/clinical status, to... (Review)
Review
PURPOSE OF REVIEW
Recent WHO guidelines recommend immediate initiation of lifelong antiretroviral therapy (ART) in all children below 5 years, irrespective of immune/clinical status, to improve access to paediatric ART. Interim trial results provide strong evidence for immediate ART during infancy because of high short-term risk of mortality and disease progression, but there is wider debate regarding the potential risks and benefits of immediate ART in asymptomatic children aged above 1 year. Concerns include long-term toxicities and treatment failure, particularly in resource-constrained settings with limited paediatric treatment options.
RECENT FINDINGS
Benefits of immediate ART among infants appear to be maintained in the mid-term to long-term, with low risk of treatment failure, and better neurodevelopmental outcomes. In contrast, a trial reported no benefits of immediate versus deferred ART in asymptomatic children aged above 1 year. However, observational studies suggest that ART initiation at older ages and lower CD4 reduces the probability of immune reconstitution, with unclear implications on risk of clinical events or treatment change. A recent trial on treatment interruption following early intensive ART suggest that this may be a safe alternative approach.
SUMMARY
Although there are clear benefits of immediate ART among infants, there remains conflicting evidence on the benefits for older children.
Topics: Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Child Development; Child, Preschool; Cognition Disorders; Drug Administration Schedule; HIV Infections; Humans; Infant; Treatment Outcome
PubMed: 24247666
DOI: 10.1097/COH.0000000000000027 -
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) Jan 2016International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose... (Review)
Review
International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones.
Topics: Anti-Retroviral Agents; HIV Infections; Humans; Travel
PubMed: 26684823
DOI: 10.1097/QAD.0000000000000920 -
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 -
Current Opinion in HIV and AIDS Jan 2015HIV genetic diversity poses major challenges for the prevention, control, and cure of infection. Characterizing the diversity and evolution of HIV populations within the... (Review)
Review
PURPOSE OF REVIEW
HIV genetic diversity poses major challenges for the prevention, control, and cure of infection. Characterizing the diversity and evolution of HIV populations within the host provides insights into the mechanisms of HIV persistence during antiretroviral therapy (ART). This review describes the HIV diversity within patients, how it is affected by suppressive ART, and makes a case for early treatment after HIV infection.
RECENT FINDINGS
HIV evolution is effectively halted by ART. However, cells that were infected prior to initiating therapy can proliferate to very high numbers both before and during treatment. Such clonal expansions result in the persistence of integrated proviruses despite therapy. These expanding proviruses have been shown to be a source for residual viremia during ART, and they may be a source for viral rebound after interrupting ART.
SUMMARY
Plasma HIV RNA shows no evidence for evolution during ART, suggesting that HIV persistence is not driven by low-level, ongoing replication. The emergence of identical viral sequences observed in both HIV RNA and DNA is likely due to proliferation of infected cells. Early treatment restricts the viral population and reduces the number of variants that must be targeted for future therapeutic strategies.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; HIV Infections; HIV-1; Humans; Virus Replication
PubMed: 25389802
DOI: 10.1097/COH.0000000000000120 -
Antiviral Therapy Oct 2023Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon... (Review)
Review
Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.
Topics: Humans; Anti-Retroviral Agents; Mutation
PubMed: 37749751
DOI: 10.1177/13596535231201162 -
Virology Apr 2014Thirty years after the identification of HIV, a cure for HIV infection is still to be achieved. Advances of combined antiretroviral therapy (cART) in recent years have... (Review)
Review
Thirty years after the identification of HIV, a cure for HIV infection is still to be achieved. Advances of combined antiretroviral therapy (cART) in recent years have transformed HIV infection into a chronic disease when treatment is available. However, in spite of the favorable outcomes provided by the newer therapies, cART is not curative and patients are at risk of developing HIV-associated disorders. Moreover, universal access to antiretroviral treatment is restricted by financial obstacles. This review discusses the most recent strategies that have been developed in the search for an HIV cure and to improve life quality of people living with HIV.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Biomedical Research; HIV Infections; Humans
PubMed: 24636252
DOI: 10.1016/j.virol.2014.02.021 -
Le Infezioni in Medicina Dec 2020Two Tenofovir pro-drugs are available for the treatment of HIV and HBV infection. Tenofovir Alafenamide (TAF) was clinically developed as a safer alternative to the...
Two Tenofovir pro-drugs are available for the treatment of HIV and HBV infection. Tenofovir Alafenamide (TAF) was clinically developed as a safer alternative to the older Tenofovir Disoproxil Fumarate (TDF) as the latter was consistently found to be associated to proximal renal tubule dysfunction and decrease in bone mineral density (BMD). As compared to TDF, the pharmacological properties of TAF are such that a more active drug is delivered into target cells while much less is measurable in general circulation. This translates into an antiretroviral action comparable to TDF with a significantly lower impact on proximal renal tubular function and bone structural integrity. The lipid-lowering effects of TDF as well as its lesser tendency to be associated to undesired body weight increase have raised some doubts about the substitution of TDF with TAF. Both issues, whose genesis is multifactorial, are strictly linked to the hypothesis of increased cardiovascular risk that might follow the switch from TDF to TAF. However, the long-term impact of decreasing renal function on cardiovascular risk must also be considered, especially in aging patients. It is thus a matter of balance: while the action on modifiable behavioural variables may well reduce lipid levels and body weight, the permanent dysfunctional pressure exerted by TDF on the proximal renal tubule could cause irreversible damage to both kidneys and bones. Therefore, all things considered, avoidance of TDF, particularly when aging patients are concerned, appears the preferable approach.
Topics: Alanine; Anti-HIV Agents; Anti-Retroviral Agents; Drug Substitution; HIV Infections; Humans; Tenofovir
PubMed: 33257626
DOI: No ID Found -
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