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Nature Reviews. Cardiology Dec 2019Antiretroviral therapy has largely transformed HIV infection into a chronic disease condition. As such, physicians and other providers caring for individuals living with... (Review)
Review
Antiretroviral therapy has largely transformed HIV infection into a chronic disease condition. As such, physicians and other providers caring for individuals living with HIV infection need to be aware of the potential cardiovascular complications of HIV infection and the nuances of how HIV infection increases the risk of cardiovascular diseases, including acute myocardial infarction, stroke, peripheral artery disease, heart failure and sudden cardiac death, as well as how to select available therapies to reduce this risk. In this Review, we discuss the epidemiology and clinical features of cardiovascular disease, with a focus on coronary heart disease, in the setting of HIV infection, which includes a substantially increased risk of myocardial infarction even when the HIV infection is well controlled. We also discuss the mechanisms underlying HIV-associated atherosclerotic cardiovascular disease, such as the high rates of traditional cardiovascular risk factors in patients with HIV infection and HIV-related factors, including the use of antiretroviral therapy and chronic inflammation in the setting of effectively treated HIV infection. Finally, we highlight available therapeutic strategies, as well as approaches under investigation, to reduce the risk of cardiovascular disease and lower inflammation in patients with HIV infection.
Topics: Anti-HIV Agents; Atherosclerosis; Coronary Disease; HIV Infections; Humans; Risk Factors
PubMed: 31182833
DOI: 10.1038/s41569-019-0219-9 -
Cell Host & Microbe Apr 2020Despite significant progress, several questions related to HIV infection remain to be addressed. Here, I provide my perspective on four key areas that need further...
Despite significant progress, several questions related to HIV infection remain to be addressed. Here, I provide my perspective on four key areas that need further research to inform curative and preventive measures against HIV/AIDS.
Topics: Acquired Immunodeficiency Syndrome; HIV; HIV Infections; Humans
PubMed: 32272074
DOI: 10.1016/j.chom.2020.03.022 -
Journal of the International AIDS... Dec 2019Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness... (Review)
Review
Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review.
INTRODUCTION
Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false-negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection.
DISCUSSION
Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified.
CONCLUSIONS
With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.
Topics: Anti-HIV Agents; HIV Infections; Humans; Male; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Viral Load
PubMed: 31850686
DOI: 10.1002/jia2.25419 -
JAMA Network Open Jun 2020Antiretroviral therapy (ART) has improved life expectancy for individuals with HIV infection, but recent data comparing life span and comorbidity-free years by HIV...
IMPORTANCE
Antiretroviral therapy (ART) has improved life expectancy for individuals with HIV infection, but recent data comparing life span and comorbidity-free years by HIV status are lacking.
OBJECTIVE
To quantify the gap in life span and comorbidity-free years by HIV status among adults with access to care.
DESIGN, SETTING, AND PARTICIPANTS
This matched cohort study used data from insured adults with and without HIV infection (aged ≥21 years) matched 1:10 at medical centers of Kaiser Permanente in northern and southern California and the mid-Atlantic states of Washington DC, Maryland, and Virginia from January 1, 2000, through December 31, 2016. Data were analyzed from September 1, 2019, through March 31, 2020.
EXPOSURES
HIV status and, for individuals with HIV infection, ART initiation at a CD4 cell count of 500/μL or greater.
MAIN OUTCOMES AND MEASURES
Overall life expectancy and expected years free of major chronic comorbidities, including chronic liver disease, chronic kidney disease, chronic lung disease, diabetes, cancer, and cardiovascular disease.
RESULTS
Of 39 000 individuals with HIV infection and 387 785 matched uninfected adults, 374 421 (87.7%) were male, with a mean (SD) age of 41.4 (10.8) years. Among 359 244 individuals with known race/ethnicity, 90 177 (25.1%) were non-Hispanic black and 87 191 (24.3%) were Hispanic. From 2000 to 2003, overall life expectancy at age 21 years of age was 37.6 years among individuals with HIV infection and 59.7 years among uninfected adults, (difference, 22.1 years; 95% CI, 20.2-24.0 years). From 2014 to 2016, overall life expectancy at 21 years of age among individuals with HIV infection increased to 56.0 years compared with 65.1 years among uninfected adults (difference, 9.1 years; 95% CI, 7.9-10.2 years). During 2011 to 2016, individuals with HIV infection who initiated ART with a CD4 cell count of 500/μL or greater had a life expectancy at 21 years of age of 57.4 years compared with 64.2 years among uninfected adults (difference, 6.8 years; 95% CI, 5.0-8.5 years). From 2000 to 2003, the expected number of comorbidity-free years remaining at 21 years of age was 11.3 for individuals with HIV infection and 26.6 years for uninfected adults (difference, 15.3 years; 95% CI, 13.9-16.6 years). This difference in comorbidity-free years persisted over time but decreased to 9.5 years (95% CI, 7.7-11.2 years) for individuals with HIV infection who initiated ART at a CD4 cell count of 500/μL or greater.
CONCLUSIONS AND RELEVANCE
The results suggest that life expectancy of adults with HIV infection may be near that of life expectancy of individuals without HIV infection, but greater attention is needed to prevention of comorbidities among individuals with HIV infection.
Topics: Adult; Chronic Disease; Cohort Studies; Comorbidity; Female; HIV Infections; Humans; Insurance, Health; Life Expectancy; Male; Middle Aged
PubMed: 32539152
DOI: 10.1001/jamanetworkopen.2020.7954 -
Current Rheumatology Reports Aug 2020To review the spectrum of vasculitides in HIV-infected patients and to identify the clinical features that characterize vasculitis in sero-positive HIV. (Review)
Review
PURPOSE OF REVIEW
To review the spectrum of vasculitides in HIV-infected patients and to identify the clinical features that characterize vasculitis in sero-positive HIV.
RECENT FINDINGS
Epidemiological studies conducted in the post-HAART era described the rarity of vasculitis in the setting of HIV-infected patients. A study identified histopathological features such as leukocytoclastic vasculitis of the vasa vasorum and adventitial inflammation in the large artery pathology of HIV-positive patients compared with HIV-negative patients with critical lower limb ischemia. A recent retrospective cohort study reported that HIV-positive patients with LVV developed more vascular complications, responded less to antiretroviral therapy, and had worse outcome than HIV-negative patients with LVV. Vasculitides continue to be a rare disease in patients with HIV. The spectrum of vasculitis ranges from life-threatening conditions to relatively mild skin conditions. Recognizing vasculitis in the setting of HIV-positive patients is important because sometimes it require immunosuppressive treatment.
Topics: HIV Infections; Humans; Polyarteritis Nodosa; Retrospective Studies; Vasculitis
PubMed: 32845496
DOI: 10.1007/s11926-020-00945-0 -
Nature Reviews. Genetics Oct 2021Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic... (Review)
Review
Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology and data science. In addition to invading cells and co-opting the host machinery for replication, HIV also stably integrates into our own genome. The study of the complex interactions between the human and retroviral genomes has improved our understanding of pathogenic mechanisms and suggested novel preventive and therapeutic approaches against HIV infection.
Topics: Genetic Variation; Genome, Human; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans
PubMed: 34168330
DOI: 10.1038/s41576-021-00378-0 -
Viruses Jan 2020Today HIV infection cannot be cured due to the presence of a reservoir of latently infected cells inducing a viral rebound upon treatment interruption. Hence, the latent... (Review)
Review
Today HIV infection cannot be cured due to the presence of a reservoir of latently infected cells inducing a viral rebound upon treatment interruption. Hence, the latent reservoir is considered as the major barrier for an HIV cure. So far, efforts to completely eradicate the reservoir via a shock-and-kill approach have proven difficult and unsuccessful. Therefore, more research has been done recently on an alternative block-and-lock functional cure strategy. In contrast to the shock-and-kill strategy that aims to eradicate the entire reservoir, block-and-lock aims to permanently silence all proviruses, even after treatment interruption. HIV silencing can be achieved by targeting different factors of the transcription machinery. In this review, we first describe the underlying mechanisms of HIV transcription and silencing. Next, we give an overview of the different block-and-lock strategies under investigation.
Topics: Animals; Clinical Trials as Topic; HIV Infections; HIV-1; Humans; Mice; Proviruses; Transcription, Genetic; Virus Activation; Virus Latency; Virus Replication
PubMed: 31936859
DOI: 10.3390/v12010084 -
EBioMedicine Mar 2022The antiretroviral treatment (ART) developed to control HIV infection led to a revolution in the prognosis of people living with HIV (PLWH). PLWH underwent from... (Review)
Review
The antiretroviral treatment (ART) developed to control HIV infection led to a revolution in the prognosis of people living with HIV (PLWH). PLWH underwent from suffering severe disease and often fatal complications at young ages to having a chronic condition and a life expectancy close to the general population. Nevertheless, chronic age-related diseases increase as PLWH age. The harmful effect of HIV infection on the individual's immune system adds to its deterioration during ageing, exacerbating comorbidities. In addition, PLWH are more exposed to risk factors affecting ageing, such as coinfections or harmful lifestyles. The ART initiation reverses the biological ageing process but only partially, and additionally can have some toxicities that influence ageing. Observational studies suggest premature ageing in PLWH. Therefore, there is considerable interest in the early prediction of unhealthy ageing through validated biomarkers, easy to implement in HIV-clinical settings. The most promising biomarkers are second-generation epigenetic clocks and integrative algorithms.
Topics: Aging; Anti-Retroviral Agents; Biomarkers; Coinfection; HIV Infections; Humans
PubMed: 35228014
DOI: 10.1016/j.ebiom.2022.103896 -
Current HIV/AIDS Reports Apr 2021Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among... (Review)
Review
PURPOSE OF REVIEW
Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among persons with HIV (PWH) initiating antiretroviral therapy (ART) in the region. In this review, we discuss the intersection of HIV infection and undernutrition, health outcomes among undernourished PWH starting ART, and the demonstrated and potential benefits of therapeutic interventions such as micro/macronutrient supplementation and pharmacological agents.
RECENT FINDINGS
A low body mass index (BMI), used as a general indicator of poor nutrition in most studies, is associated with impaired immune recovery and increased mortality in the early ART period. The increased risk of mortality is multifactorial, and contributors include undernutrition-related immune system dysfunction, increased susceptibility to opportunistic infections, and metabolic and cardiovascular dysregulation. Clinical trials of micro/macronutrient supplementary feeding, appetite stimulants (hormones and anabolic agents), and recombinant adipokines have shown a benefit for weight gain and metabolic health, but there are few data on mortality or immune recovery. A substantial proportion of PWH in SSA are undernourished, and undernutrition contributes to an increased risk of mortality and other adverse health outcomes. To date, there have been few prospective trials of nutritional supplementation and/or pharmacologic therapy among undernourished PWH in SSA, though findings from other settings suggest a potential benefit in this population.
Topics: Africa South of the Sahara; HIV Infections; Humans; Malnutrition; Outcome Assessment, Health Care; Prospective Studies
PubMed: 33606196
DOI: 10.1007/s11904-021-00541-6 -
AIDS (London, England) Mar 2021People living with HIV are at higher risk for acute and chronic kidney disease compared with uninfected individuals. Kidney disease in this population is multifactorial,... (Review)
Review
People living with HIV are at higher risk for acute and chronic kidney disease compared with uninfected individuals. Kidney disease in this population is multifactorial, with several contributors including HIV infection of kidney cells, chronic inflammation, genetic predisposition, aging, comorbidities, and coinfections. In this review, we provide a summary of recent advancements in the understanding of the mechanisms and implications of HIV infection and kidney disease, with particular focus on the role of direct HIV infection of renal cells.
Topics: Comorbidity; HIV Infections; HIV-1; Humans; Kidney; Kidney Diseases
PubMed: 33229896
DOI: 10.1097/QAD.0000000000002753