The search for the role(s) that HIV-1 Vpr and its HIV2/SIV paralogs Vpr and Vpx play in viral infection and pathogenesis showed that all three engage CRL4 ubiquitin ligase complexes. This association triggers ubiquitination and degradation of cellular substrates. The identity of the ubiquitin ligase substrates is only now beginning to be revealed. This review focuses on recent work that has identified one such substrate and exposed new cellular restrictions to infection.
Three groups have now described cellular factors that restrict HIV-1 infection in cells of the myeloid lineage. One of these factors, SAMHD1, was shown to be depleted through the CRL4 ubiquitin ligase complex in the presence of HIV-2/SIV Vpx. The other restriction can be defeated by Vpx in the absence of at least one part of the ubiquitin ligase complex that triggers SAMHD1 depletion.
Another group has shown that the previously-described up-regulation of NK-cell ligands on the surface of HIV-1-infected cells requires the actions of both the cytidine deaminase APOBEC3G and uracil-N-glycosylase 2 in association with HIV-1 Vpr.
As more cellular interaction partners are identified for HIV-1 Vpr and its paralogs from other viruses, details are emerging about Vpr function. The recent findings have highlighted the existence of two new human proteins that can act to combat HIV infection and have revealed how HIV-1 proteins act in concert to modulate the interaction between NK cells and HIV-1 infected cells.
HIV; SIV; Vpr; Vpx; SAMHD1
Purpose of review
We will summarize recent advances in research regarding control of simian immunodeficiency virus (SIV) replication in non-human primate models. We will then relate these findings to the broader field of human immunodeficiency virus (HIV) vaccine development.
Recent studies have highlighted the importance of T cell responses in elite control, especially CD8+ T cell responses, and provide insight into the kinetics and qualities of such effective responses. Additionally, these findings suggest that the peptides bound by elite control-associated MHC class I molecules in monkeys and humans share many properties.
Animal models of effective immune control of immunodeficiency virus replication have provided important insight into the components of successful immune responses against these viruses. Similarities between the human and non-human primate responses to immunodeficiency viruses should help us understand the nature of elite control. Further study of the acute phase, where virus replication is first brought under control may help define important characteristics of viral control that could be engendered by a successful HIV vaccine.
CD8+ T cell; elite control; animal model; immune control
Purpose of review
Interest in finding a potential ‘cure’ for HIV has taken on greater interest and urgency since the report of an individual who underwent allogeneic stem cell transplant from a CCR5 delta 32 homozygote donor after high-dose chemotherapy for acute myeloid leukemia. The potential role of cancer chemotherapy and other cancer-directed treatment approaches is discussed in the context of their potential role in helping to eliminate HIV from the infected host.
Cancer chemotherapy and other cancer-targeted agents have been used successfully in treating a variety of malignancies in both HIV-infected and HIV-uninfected individuals. Lessons learned from these strategies may be of importance in helping to define more effective ways of controlling and eliminating HIV as well. Application of these anticancer strategies to patients with HIV are beginning to be explored and may help determine their potential usefulness in this disease as well.
Although cytotoxic chemotherapy is a crude and not particularly effective way of removing HIV latently infected cells and tissue reservoirs, several new approaches to targeting and controlling cancer proliferation may be of value in HIV cure research and may one day help to end this disease.
adoptive cell therapy; chemotherapy; epigenetic manipulation; immunotoxin; stem cell transplant
Purpose of review
The purpose of this review is to highlight new findings published in 2010-11 related to noninvasive fibrosis assessment in HIV/HCV co-infected patients. Overall, in 2010-11, 15 papers were published, of which two were excluded because they were published in languages other than English.
11 papers focused on serum marker panels. Papers sought to either 1) validate established panels in HIV/HCV co-infected patients often by comparing multiple serum marker panels in the same population; 2) establish new marker panels using combinations of markers used in previously validated panels; and 3) develop new marker panels using novel methodology. Overall, all panels performed within similar ranges of diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AUROC) but the Fibrometer panel and its derivations achieved the highest performance. Four studies focused on transient elastography (TE). Two papers confirmed its accuracy for identifying fibrosis and cirrhosis and two papers confirmed that misclassification rates are higher in the presence of elevated triglycerides and steatosis.
Overall, performance of TE appeared superior to the majority of serum marker panels for the detection of significant fibrosis and cirrhosis in HIV/HCV co-infected patients. Challenges of widespread application of TE remain high misclassification in some subgroups, lack of standardized cutpoints and lack of widespread availability. Panels that were newly developed in 2010-11 specifically for HIV/HCV appeared to perform better than existing panels such as APRI and FIB-4; however additional external validation will be needed to confirm their accuracy.
hepatitis C virus; liver fibrosis; HIV; elastography; serum markers
Purpose of review
We review recently published literature concerning early morbidity and mortality during antiretroviral therapy (ART) among patients in resource-limited settings. We focus on articles providing insights into this burden of disease and strategies to address it.
In sub-Saharan Africa mortality rates during the first year of ART are very high (8%-26%), with most deaths occurring in the first few months. This compares to 3%-13% in programmes in Latin America and the Caribbean and 11%-13% in South-East Asia. Risk factors generally reflect late presentation with advanced symptomatic disease. Key causes of morbidity and mortality include tuberculosis, acute sepsis, cryptococcal meningitis, malignancy, wasting syndrome/chronic diarrhoea. Current literature shows the fundamental need is for much earlier HIV diagnosis and initiation of ART. In addition, further studies provide data on the role of screening and prophylaxis against opportunistic diseases (particularly TB, bacterial sepsis and cryptococcal disease) and the management of specific opportunistic diseases and complications of ART. Effective and sustainable delivery of these interventions requires strengthening of programmes.
Strategies to address this disease burden should include earlier HIV diagnosis and ART initiation, screening and prophylaxis for opportunistic infections, optimised management of specific diseases and treatment complications, and programme strengthening.
HIV; antiretroviral; mortality; death; morbidity; resource-limited; low-income
Purpose of review
The persistence of HIV within infected CD4+ T cells is a major obstacle to eradication, and assessment of the strategies to reduce HIV reservoirs is one of the major challenges. Measuring HIV reservoirs accurately will be necessary to assess those strategies. The objective of this review is to present the most recent studies that may help to define the best markers to measure HIV reservoirs.
Recent findings have shown that multiple assays can be used to quantify the different analytes that reflect the HIV reservoirs. They have provided new insights, but lack of standardization has made cross-comparisons of data difficult. No single best assay for measuring HIV reservoirs has been identified and these assays often address different questions, such as the size of the reservoirs, the composition of the reservoirs, or the capacity of latent reservoirs to produce virus. A consensus on what values reflect robust conclusions will have to wait for the generation of additional results.
In conclusion, there is a compelling need for investigators to optimize assays and share protocol reagents and specimens to permit the validation, comparison, and standardization of techniques. There is an important need for validated, high-throughput, sensitive, and accurate assays that can detect changes in HIV reservoir size in order to assess the impact of candidate therapies.
HIV latency; markers of HIV reservoirs; quantification
Purpose of Review
The purpose of this paper is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir and elvitegravir (both in Phase III drug development).
Data from January 2011 to April 2012 were evaluated. These data better characterized integrase inhibitor pharmacokinetics, assessed dosing regimens and investigated previously undescribed drug-drug interactions. Due to formulation challenges, raltegravir inter- and intra-patient pharmacokinetic variability is high. Twice daily 400mg dosing has been shown to be clinically superior to 800mg once daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was FDA approved in December 2011. Cobicistat-boosted elvitegravir, and the second generation integrase inhibitor dolutegravir, have lower pharmacokinetic variability and are dosed once daily. Dolutegravir drug interactions are similar to raltegravir, while boosted elvitegravir participates in additional CYP3A mediated interactions.
Raltegravir’s potent antiretroviral activity has resulted in widespread use in both treatment naïve and experienced patients. Dolutegravir and cobicistat-boosted elvitegravir have some pharmacokinetic advantages. Pharmacokinetic data in special populations (pregnancy, pediatrics) to optimize dosing are still required.
HIV Integrase Inhibitors; Raltegravir; Dolutegravir; Elvitegravir
Purpose of review
Measurements of HIV burden have relied upon quantification of viral nucleic acids by real-time PCR (qPCR). To develop and test strategies for eradication, new methods are needed to better characterize residual cellular reservoirs in patients on suppressive antiretroviral therapy (ART). This review summarizes recent advances that may lead to clinically useful tests with improved sensitivity, reproducibility and throughput.
HIV DNA remains the most sensitive measure of residual infection, but its low levels are difficult to differentiate from assay noise by qPCR. Digital PCR has begun to improve the precision of existing real-time assays, but there remains a need to distinguish replication-competent proviruses. Rapid technological progress in single-cell analysis is beginning to offer new approaches, notably CyTOF and microengraving, which could provide vastly more information about the composition of the latent reservoir.
To investigate and assess therapies directed towards eradication, improved assays that simultaneously offer high sensitivity, precision and information content will be needed.
cytometry via time of flight; droplet digital PCR; digital PCR; eradication; HIV DNA; HIV latency; microengraving; single-cell analysis
Clinical trials of oral pre-exposure prophylaxis (PrEP) have focused testing on regimens of tenofovir (TDF) with or without emtricitabine (FTC). However, TDF may be associated with toxicities (renal, bone) and FTC may select for drug resistance. In this review, we discuss agents that might serve as alternatives to TDF/FTC for HIV prevention.
Several drug characteristics are important to consider when selecting agents for PrEP with the most critical being safety, tolerability, adequate penetration into target tissues, prevention of HIV infection, and long lasting activity with convenient dosing. With these factors in mind, we review several potentially useful agents for PrEP. The first group includes drugs that are already FDA-approved (maraviroc, raltegravir) with attributes that make them attractive for PrEP. The second groups of drugs include investigational agents with long-lasting activities that are being developed in parenteral form (rilpivirine-long acting, S/GSK 1265744, ibalizumab).
Current research suggests there will be a broader array of PrEP drugs to choose from in the near future, thereby giving clinicians the flexibility to select agents that best suit the needs of their patient population.
HIV PrEP; maraviroc; raltegravir; rilpivirine; S/GSK 1265744; ibalizumab
Purpose of review
Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples.
Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence.
For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission.
antiretrovirals as prevention; conception; fertility; HIV prevention; HIV-serodiscordance; perinatal HIV transmission; sexual HIV transmission
Purpose of review
This work focuses on the use of antiretroviral agents to prevent the sexual transmission of HIV-1.
Two randomized clinical trials demonstrated that antiretroviral agents provided before exposure to HIV-1 offer substantial protection, ostensibly directly proportional to the concentration of antiretroviral therapy (ART) in the genital secretions. Intense focus on the use of HIV treatment as prevention has led to publication of modeling exercises, ecological studies, and observational studies, most of which support the potential benefits of ART. However, the logistical requirements for successful use of ART for prevention are considerable.
ART will serve as a cornerstone of combination prevention of HIV-1. Continued research will be essential to measure anticipated benefits and to detect implementation barriers and untoward consequences of such a program, especially increases in primary ART resistance.
antiretroviral therapy; pre-exposure prophylaxis; prevention
Purpose of review
To examine the consequences of the immune modulation seen in chronic filarial infection on responses to intracellular pathogens (and their antigens) that are often co-endemic with filarial infections, namely Plasmodium and Mycobacterium tuberculosis.
Much of the recent data on filaria/mycobacteria or filaria/Plasmodium co-infection has focused on the modulation of mycobacteria-specific or malaria-specific responses by chronic filarial infection. As such, filarial infections very clearly alter the magnitude and quality of the mycobacteria-specific or malaria-specific cytokine responses, responses that have been typically associated with control of these intracellular pathogens.
Although phylogenetically distinct, mycobacteria and Plasmodium spp. often share the same geographical niche with filarial infections. The complex interplay between filarial parasites that are associated with immunomodulation and those microbial pathogens that require a proinflammatory or unmodulated response for their control is easily demonstrable ex vivo, but whether this interplay affects disease outcome in tuberculosis or malaria remains an open question.
filarial infections; immunomodulation; malaria; tuberculosis
Purpose of review
Several unique HIV-infected or HIV-resistant cohorts have been studied over the years to try and delineate the correlates of protection. Although several mechanisms have been put forward, studies aiming to integrate the different mechanisms into a comprehensive model are still lacking. Current systems biology approaches emphasize the importance of unifying independent datasets, provide tools that facilitate hypothesis formulation and testing, and direct us toward uncovering novel therapeutic targets by defining molecular networks perturbed during disease. This review will focus on the current findings that utilized systems biology techniques in order to identify correlates of protection from HIV disease progression and resistance to infection in unique cohorts of individuals as well as in nonhuman primate models of SIV infection.
Using systems biology technologies and data analysis tools, the studies described herein have found that pathways implicated in survival, cell cycling, inflammation, and oxidative stress work in unison to limit pathology caused by chronic immune activation. This situation favors the survival of effector lymphocytes and limits the dissemination of viral particles in HIV elite controllers, exposed-uninfected individuals, and natural hosts of SIV infection.
Systems and computational biology tools have clearly expanded our understanding of HIV pathogenesis by unifying independent observations and by giving us novel molecular targets to pursue. These molecular signatures have the potential to uncover correlates of protection in HIV disease and, in the era of personalized medicine, to determine predictive signatures of treatment efficacy and/or failure.
elite controllers; exposed-uninfected; HIV; networks; pathways; resistance; systems biology
Purpose of review
This review summarizes the development and implementation of a large clinical trial, HIV Prevention Trials Network (HPTN) 052, whose initial results were recently presented and published.
A randomized, clinical trial demonstrated that antiretroviral therapy reduces the sexual transmission of HIV in HIV-serodiscordant couples by more than 96%. The logistical challenges in preparing for and conducting such a trial were considerable.
HPTN 052 required many years of preparation, considerable collaboration between National Institute of Health and six pharmaceutical companies, and careful ongoing consideration of a large number of ethical issues. HPTN 052 revealed the magnitude of benefit when using antiretroviral therapy to prevent the transmission of HIV, and served as proof of a concept. The results have proven central to the development of new global HIV-prevention efforts.
antiretroviral therapy; prevention; transmission
Lymphoma remains a leading cause of mortality in HIV infected patients. In the HIV negative setting high dose therapy with autologous stem cell rescue (ASCT) has been a long accepted treatment for certain malignancies such as lymphoma and leukemia. Early transplant trials excluded older patients, and patients with comorbidities such as HIV infection. However, the procedural related mortality of transplantation has decreased both due to the use of peripheral blood stem cells instead of bone marrow and due to the use of new reduced intensity conditioning regimens. During this same era, the treatment of HIV infection has also become more effective. Patients are no longer dying of opportunistic infections and in addition, their hematologic function has improved.
With these advances in HIV therapy it is possible for HIV infected patients to mobilize adequate numbers of stem cells for an autologous transplant. In addition, with appropriate antiretroviral therapy and infection prophylaxis, the HIV infected patient can tolerate intensive doses of chemotherapy. This review will summarize clinical trials of ASCT in HIV positive patients. Furthermore, the field of solid organ transplantation has grown to also include HIV positive patients. The challenges in solid organ transplantation are similar to allogeneic stem cell transplantation, namely that patients require chronic immunosuppression. This article will also review some of the approaches to allogeneic stem cell transplantation in the HIV positive patient and provide a rationale for the broader use of stem cell transplantation for appropriate HIV related hematologic malignancies.
Autologous transplant; Allogeneic Transplant; Lymphoma
Purpose of review
The purpose of this review is to describe a critical need of the HIV research community for a globally accessible database of HIV vaccine responses that stores data from multiple assay platforms in the form of lists of correlates of immune protection and vaccine efficacy. This is not a detailed review but a first step toward developing a dialogue among investigators and funding organizations to build upon existing resources to efficiently develop a HIV vaccine response and correlates database. We also discuss examples of databases that complement our needs and could be integrated into our proposed database requirements.
Several vaccine-related databases that store information at the study level currently exist, however, at the present time, a correlates of immune protection database does not exist.
Here, we discuss the scientific climate surrounding HIV vaccine development with the evolution of systems biology approaches, the problems at hand for analyzing and harmonizing datasets generated from preclinical and clinical studies, and the curation and accessibility of useful information to model outcomes. We also compare key database requirements of a few existing globally accessible databases and provide several illustrative correlate database submission and utilization examples.
correlates; database; HIV; immune responses; vaccine
Purpose of review
The use of systems biology approaches to understand and predict vaccine-induced immunity promises to revolutionize vaccinology. For centuries vaccines were developed empirically, with very little understanding of the mechanisms by which they mediate protective immunity. The so-called systems vaccinology approach employs high-throughput technologies (e.g. microarrays, RNA-seq and mass spectrometry-based proteomics and metabolomics) and computational modeling to describe the complex interactions between all the parts of immune system, with a view to elucidating new biological rules capable of predicting the behavior of the system.
Systems biology successfully applied to yellow-fever and influenza vaccines has led to the discovery of signatures that predict vaccine immunogenicity, and promises to advance basic immunology research by providing novel mechanistic insights about immune regulation. However a major challenge of systems vaccinology concerns the analyses and interpretation of the large and noisy data sets generated by high-throughput techniques. Overcoming these issues, we envision that systems vaccinology will have a potential impact on vaccine development, including HIV vaccines.
High-throughput technologies allow the investigation of vaccine-induced immune responses at system and molecular levels. These are currently being used to unravel new molecular insights about the immune system, and are on the verge of being integrated into clinical trials to enable rational vaccine design and development.
blood transcriptomics; systems biology; systems vaccinology; vaccinology
Purpose of Review
The recent modest success of the RV144 HIV vaccine trial in Thailand has shown that development of an HIV vaccine is possible. Designing a vaccine that achieves better protection, however, will require a more complete understanding of vaccine mechanisms of action and correlates of protection. Systems biology approaches enable integration of large datasets from a variety of assays and offer new approaches to understanding how vaccine-induced immune responses are coordinately regulated. In this review, we discuss recent advances in clinical trial design, specimen collection, and assay standardization that will generate datasets for systems analyses of immune responses to HIV vaccines.
Several recently-published HIV vaccine trials have shown that different HIV vaccine prime/boost combinations can greatly affect the immune response generated, but mechanistic insights into their modes of action are lacking. Novel systems biology studies of efficacious, licensed vaccines provide a new template for analysis of HIV vaccines. To generate datasets appropriate for systems analysis, current HIV vaccine clinical trials are undergoing design modifications and increased standardization of specimen collection and immune response assays.
Systems biology approaches to HIV vaccine evaluation are driving new methods of HIV vaccine immune response profiling in clinical trials, and will hopefully lead to new improved HIV vaccines in the near future.
HIV vaccine; systems biology; clinical trials; assay standardization
Purpose of review
This review will discuss the use of systems biology approaches to dissect the heterogeneity of the HIV-specific CD8+ T cell response.
New experimental approaches have allowed complex phenotypes of individual cells present in the human antigen-specific CD8+ T cell response to be characterized. Genome-wide measurements of gene expression in antigen-specific T cells have created broad molecular phenotypes of the T cell response to HIV. Pattern recognition algorithms to discover new sub-classes of samples in microarray datasets are becoming increasingly sophisticated. Together, these advances now allow the heterogeneity of the T cell response to HIV to be unraveled.
The phenotype antigen-specific T cells responding to pathogens like HIV in humans is seen as much “noisier” than in animal models of infection. However, applying new systems biology tools may provide an opportunity to identify the sources of this “noise” as novel, biologically distinct sub-classes of CD8+ T cell response to HIV.
HIV; heterogeneity; genomics; single-cell
Purpose of Review
Failure to control viral infections such as HIV, results in TCR and inhibitory receptor driven exhaustion of antigen-specific T cells. Persistent signaling by these receptors during chronic viral infection sculpts the transcriptional regulatory programs of virus-specific T cells. The resulting gene expression profile is tailored to temper the potentially damaging effector functions of cytotoxic T cells and adapt them to an antigen and inflammation rich environment. Here we review recent studies investigating mechanisms of transcriptional regulation of effector, functional memory, and exhausted T cell functions during acute versus chronic infections.
Patterns of gene expression in virus-specific CD8 T cells are a result of a combination of pro and inhibitory signals from antigen presentation (TCR-mediated) and co-inhibitory receptor ligation (PD-1, 2B4). Further, memory-specific transcriptional regulation of 2B4 expression and signaling impose a self-limiting secondary effector response to a prolonged viral infection. Additionally, differentiation of functional memory CD8 T cells is coupled to acquisition of a repressive epigenetic program for PD-1 expression. However, chronic infection provides a signal which blocks the acquisition of these epigenetic modifications reinforcing the suppression of CTL functions in exhausted cells.
Current findings suggest that the mechanism(s) that delineate functional memory versus exhaustion are coupled to acquisition of transcriptional programs at the effector stage of differentiation, reinforced by cessation or persistence of TCR signaling.
Chronic Infection; CD8 T cell; Exhaustion; Transcription Factor; Epigenetic
Purpose of review
Major roadblocks persist in the development of vaccines that elicit potent neutralizing antibodies targeting diverse HIV-1 strains, similar to known broadly neutralizing HIV-1 human monoclonal antibodies. Alternatively, other types of anti-HIV-1 envelope antibodies that may not neutralize HIV-1 in traditional neutralization assays but have other anti-HIV-1 activities (hereafter termed HIV-1 inhibitory antibodies) can be elicited by current vaccine strategies, and numerous studies are exploring their roles in preventing HIV-1 acquisition. We review examples of strategies for eliciting potentially protective HIV-1 inhibitory antibodies.
Heterologous prime-boost strategies can yield anti-HIV immune responses; although only one (canarypox prime, Env protein boost) has been tested and shown positive results in an efficacy trial (RV144). Although the immune correlates of protection are as yet undefined, the reduced rate of acquisition without a significant effect on initial viral loads or CD4+ T cell counts, have raised the hypothesis of an RV144 vaccine-elicited transient protective B cell response.
In light of the RV144 trial, there is a critical need to define the entire functional spectrum of anti-HIV-1 antibodies, how easily each can be elicited, and how effective different types of antibody effector mechanisms can be in prevention of HIV-1 transmission.
Vaccines; B-cells; Neutralizing Antibodies; Inhibitory Antibodies; Mucosal
Purpose of review: describe why this review is timely and relevant
An estimated 33 million people are living with Human Immunodeficiency Virus (HIV) and Universal Access remains a dream for millions of people. By end 2008, 4 million people were on treatment, however, over 5 million needed treatment and in 2007 there were 2.7 million new infections. Without significant improvement in prevention, we are unlikely to meet universal access targets including the growing demand for highly active antiretroviral treatment (HAART). This review examines HAART as a potential tool for preventing HIV transmission
Recent findings: describe the main themes in the literature covered by the article
We discuss recent scientific evidence regarding the treatment and prevention gap, importance viral load and HIV transmission, HAART and HIV transmission, when to start, HIV counseling and testing, modeling results and next steps.
Summary: describe the implications of the findings for clinical practice or research
HAART has considerable treatment and prevention benefits and it needs to be is considered as a key element of combination prevention. To explore HAART as an effective prevention strategy we recommend further evaluation of human rights and ethical considerations, clarification of research priorities and exploration of feasibility and acceptability issues.
HAART; HIV; prevention; universal access; modeling
Purpose of Review
Highly active antiretroviral therapy (HAART) use has markedly reduced AIDS-related mortality and opportunistic illness. With improved survival, cardiovascular disease (CVD) has emerged as an important non-infectious chronic co-morbidity among antiretroviral (ARV)-treated HIV-infected persons.
HIV infection can impact CVD and co-morbidiities known to increase CVD risk. Untreated HIV can cause proatherogenic elevations in serum lipids. Chronic HIV viremia results in increases in systemic inflammation, hypercoagulation, and reductions in endovascular reactivity, all of which are at least partially reversible with virally suppressive HAART. Chronic T cell activation can also result in adverse vascular effects. Use of some ARV drugs can impact CVD risk by causing pro-atherogenic serum lipid elevations, induction of insulin resistance, increases in visceral adiposity or subcutaneous fat loss. Abacavir use may increase myocardial infarction risk by reducing vascular reactivity and/or increasing platelet activation. Traditional risk factors such as advancing age, smoking, hyperlipidemia, and hypertension remain important predictors of CVD among HAART-treated HIV-infected persons.
HIV in the HAART era is a chronic manageable condition. CVD is an important cause of morbidity among HIV-infected persons. Untreated HIV can increase CVD risk in several ways and these effects are at least partially reversible with successful treatment. Use of specific ARV’s can adversely impact CVD risk but the multiple long-term benefits of chronic HIV suppression and immune reconstitution achievable with potent HAART outweigh the adverse impact upon CVD risks that they may have. Standard CVD screening and risk-reducing interventions should be routinely undertaken for HIV-infected persons.
Cardiovascular disease in HIV infection; Inflammation; hypercoagulation; vascular functioning; Effects of antiretroviral drugs; Hyperlipidemia