Abstract supplement: HIV Drug Therapy in the Americas Congress 13–15 June 2013, São Paulo, Brazil

Abstract

Journal of the International AIDS SocietyVolume 16, Issue 2S1 18720 Abstract SupplementOpen Access HIV Drug Therapy in the Americas Congress, 13 – 15 June 2013, São Paulo, Brazil First published: 13 June 2013 https://doi.org/10.7448/IAS.16.2.18720Citations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Keynote Lectures Abstract Introduction Antiretroviral therapy (ART) can sustain suppression of plasma viremia for years. However, if therapy is interrupted, there is a rapid resumption in viremia. Therefore, HIV-1 has the ability to persist in the face of potent ART. Identifying the mechanism through which HIV-1 persists in infected individuals on suppressive therapy is central to the goal of curing infection in these individuals. For this reason, research is focused on establishing tools with which to probe the reservoirs that persist in aviremic individuals as well as clinical protocols with which to perturb those reservoirs. How we measure viral reservoirs in aviremic patients and, as a consequence, how we gauge the impact of treatments on those reservoirs is a contentious issue. Most attention has focused on the role of latently infected T-cells in viral persistence and clinical strategies are geared towards purging of these reservoirs. However, other factors may be contributing to viral persistence including residual viral replication and establishment of non-T-cell reservoirs. In addition, although ART significantly improves health outcomes for the patient, several markers of immunopathogenicity persist in the face of effective viral suppression and drive comorbidities. The underlying cause of ongoing pathogenicity in the face of effective ART is unclear. Studies examining the impact of treatment intensification on markers of viral pathogenicity will be discussed. 10.7448/IAS.16.2.18687 © 2013 Stevenson M; licensee International AIDS Society Published 13 June 2013 Keynote Lectures Citing Literature Abstract The efficiency of transmission of HIV depends on the infectiousness of the index case and the susceptibility of those exposed. Infectiousness is dictated by the concentration of HIV-1 in relevant fluids (regardless of route of transmission) and the viral genotype and phenotype. People newly infected with HIV-1 (i.e. acute infection) and those with STD co-infections excrete such a large concentration of virus as to be “hyperinfectious”. The actual transmission of HIV likely occurs in the first few hours after exposure. The probability of transmission may be as low as 1/10,000 episodes of intercourse or 1/10 sexual exposures when anal intercourse is practiced. The transmission of HIV is generally limited to one or a small number of founder variants which themselves may be “hyperinfectious”. Synergistic behavioural and biologic HIV prevention strategies have been developed and implemented. Safer sex includes limiting the number of sexual partners, use of male latex condoms, and structural interventions to reduce exposure. These strategies appear to have contributed to reduced HIV incidence in many countries. Biological interventions have proven catalytic: these include treatment of inflammatory cofactors, voluntary male circumcision, and use of antiviral agents either for infected people (who can be rendered remarkably less contagious) or as pre- and post-exposure prophylaxis (PrEP and PEP). Ecologic evidence suggests that broader, earlier antiviral treatment of HIV may be reducing incidence in some (but not all) populations. However, maximal benefit of HIV “treatment for prevention” and application of PrEP will likely require a program of universal “test and treat”, where many more infected patients are identified, linked to care, and treated very early in disease and for life. Community randomized trials designed to support this approach are underway in Africa. The “test and treat” prevention strategy is resource intensive and serves to emphasize research that searches for a cure for HIV infection, so that HIV infected people can eventually reduce or stop treatment. Likewise, success in HIV prevention emphasizes the importance of development of an HIV vaccine, which remains focused on agents that may evoke CTL responses, antibody-dependent cytotoxicity, and (perhaps most important) broad neutralizing antibodies. A human clinical trial (RV144) and animal experiments have provided hope, excitement, and a roadmap for development of an HIV vaccine. 10.7448/IAS.16.2.18688 © 2013 Cohen M; licensee International AIDS Society Published 13 June 2013 Keynote Lectures Citing Literature Abstract Latin America is globally recognized for achieving high coverage of antiretroviral treatment. Virtually all countries in the region have been able to achieve this important goal by offering universal access to antiretroviral drugs through their public health systems, despite the fact that antiretrovirals are available for these countries at relatively high prices, compared to other low- and middle-income countries. However, even though it would be fair to say that the access problem has been solved in the region, there are other important challenges that need to be strategically addressed. Both treatment and prevention programmes in our countries urgently need to be optimized, which means that although the infrastructure and capacity to implement highly effective programmes already exist, but the challenge now is to increase quality and efficiency. During this presentation, I will address some of the aspects, both programmatic and economic, that appear to be the most pressing ones requiring our attention, and also discuss some of the alternatives available to us toward improving the performance of our programmes. On the treatment side, I propose that there are likely large potential gains in improving timeliness of treatment initiation and efficiency of treatment regimes. On the prevention side, significantly improving testing efforts and increasing their coverage is probably a good measure toward increasing the health gains of our efforts. Using evidence to address these issues is key, and I wish to put to you that not only have we not done it enough in the past but that we also urgently need to generate evidence upon which to base our decisions. Most of the scientific evidence on the prevention realm comes from Africa. We need to be more creative and innovative and rigorously evaluate approaches to improve access, quality and efficiency. 10.7448/IAS.16.2.18689 © 2013 Bautista S; licensee International AIDS Society Published 13 June 2013 Keynote Lectures Citing Literature Abstract Once a retrovirus infects a eukaryotic cell and integrates within chromosomal DNA, it becomes part of its genome and can be activated/transcribed/translated to produce viral proteins and/or new viral particles. Over the years, some of these retroviruses may lose their pathogenicity and become adapted to the new host. Under these conditions, retroviruses can paradoxically ameliorate the functional portfolio of the infected cell, thus potentially increasing its functionality and/or chances of survival in a difficult environment. Individuals whose cells are infected by retroviruses have acquired, in the last millions of years, innovative functions that, once transmitted to the new generation through germinal cells, have become essential for their homeostasis, or even for their survival. This is the case of some endogenous retroviruses, whose products are mandatory for the proper vascularization of human placenta. To our knowledge, there are no natural means able to selectively eliminate retroviral genes from an infected cell or an individual. Therefore, chances of getting naturally cured by retroviruses, once infection is set and viral genomes are spread into the body, are minimal or absent. HIV is a retrovirus that behaves as all other retroviruses that interacted with humans in the past millennia. Its fate is to remain forever within the infected body. For these reasons, chances of getting rid of HIV infection and being biologically cured (that is, eliminating all viral genomes from the body) are very limited if we consider current knowledge, biotechnology, and available medical tools (yet it cannot be fully excluded in very peculiar cases). The option offered by the so called “functional cure” is different. In this case, medical manipulation may create conditions whereby viral genomes, decreased in number and function by proper therapies/vaccines, are no longer able to harm the host for an indefinite period of time. Patients do remain infected, but viral replicative cycles are absent, and progression of the disease is interrupted. This latter clinical approach may be suitable, and this is where the clinical research is directing its efforts. If achievable, infected persons should cope with the virus and keep it under control for decades, without support of chronic antiviral therapy. In conclusion, the proper knowledge of the biological characteristics of HIV helps in selecting the best strategies aimed at obtaining the maximum achievable clinical result. 10.7448/IAS.16.2.18690 © 2013 Perno C-F; licensee International AIDS Society Published 13 June 2013 Oral Abstracts O11–Update on Antiretrovirals and Treatment Strategies Citing Literature Abstract The collaborative international effort to provide universal access to HIV care and effective antiretroviral therapy (ART) has reached a critical time point. The global economic downturn, changing donor priorities and competing priorities in the health sector threaten the capacity of various agencies to maintain support for the continued scale-up of access toward the UN General Assembly-agreed target of 15 million people with HIV/AIDS receiving ART by 2015. We now know that treatment acts as prevention by reducing the infectiousness of treated individuals. It is now necessary to review the elements of the successes and challenges to date, in order to be able to best use finite resources. These elements include efforts to optimize the delivery of HIV care, including ART, in low- and middle-income countries (LMIC) and the emergence of new agents and drug classes, which have simplified HIV treatment and made broader successful management more achievable. Recent studies have indicated that earlier commencement of HIV therapy is beneficial, leading to changes in the recommended ART initiation threshold in LMIC to <350 CD4 T cells. Forthcoming revised WHO guidelines are anticipated to raise this threshold. Studies currently under way are investigating approaches to second-line ART in LMIC. The results from these studies will better inform the roll-out of effective second-line therapy. In addition, the financial cost of ART makes optimization of dosing an important consideration in LMIC, in order to maximize effectiveness while limiting costs. ART monitoring is also an important priority in LMIC. Efforts to develop simple and reliable technologies that can provide rapid results in the field are underway. In the meantime, a number of recent studies in adults and children point to the way forward and the best use of resources. The final priority is operational optimization, to ensure adequate service delivery. Although the challenges in LMIC are substantial and evolving, considerable inroads have been and are being made into optimizing HIV treatment and its delivery, which is crucial in reducing the global impact of the disease. This abstract is modified from an abstract provided by David Cooper, University of New South Wales, Sydney, Australia, when presented as the Lock Lecture at HIV Drug Therapy in Glasgow, November 2012. 10.7448/IAS.16.2.18691 © 2013 Weller I; licensee International AIDS Society Published 13 June 2013 Oral Abstracts Citing Literature Abstract There currently are 27 antiretroviral drugs approved for the treatment of HIV infection. In choosing the optimal initial regimen, a number of factors should be considered: antiretroviral activity (HIV RNA, CD4 cell, and clinical responses); durability of responses; baseline drug resistance; tolerability and both acute and chronic side effects; convenience (number of pills, dosing interval, food/fasting requirements); preserving future treatment options; patient's stage of HIV disease, concomitant illnesses and medications (and drug-drug interactions); access; and cost. The optimal initial regimen is one that is individualized to the specific patient's situation. Current preferred initial regimens include two nucleoside analogues (NRTI) combined with either a non-nucleoside analogue (NNRTI), a boosted protease inhibitor (PI), or an integrase inhibitor (II). One-pill, once-daily combination regimens have proven particularly popular with patients and providers alike. The most common initial regimen worldwide is two NRTI + an NNRTI. In the event of virologic failure of an initial regimen, multiple causes of failure should be assessed, including: adherence; drug resistance; use of less potent antiretroviral regimens; drug levels and drug-drug interactions; and theoretically, tissue reservoir penetration (central nervous system, genital tract). Of course, any or all of these reasons may be important and the challenge is to address the probable cause(s) of failure and address them in choosing the next regimen, to ensure success. Genotypic drug resistance testing is indicated in the assessment of first (or second) virologic failure and can help optimize the selection of the next regimen. Genotypic and phenotypic testing is recommended following failure of multiple regimens. A common sequence of regimens is two NRTI and an NNRTI, changing to two NRTI + a boosted PI. The availability of drugs with activity against drug-resistant viruses (e.g. newer NNRTIs and PIs) and new classes of drugs (e.g. integrase inhibitors, CCR5 antagonists) offers additional options for constructing successful subsequent ART regimens. 10.7448/IAS.16.2.18692 © 2013 Gulick R; licensee International AIDS Society Published 13 June 2013 Oral Abstracts Citing Literature Abstract HIV resistance to ARV therapy is an unwanted consequence of HAART as it limits future options. The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up, without proper treatment monitoring and drug availability, could compromise the effectiveness of national HIV treatment programmes. Compared to developed countries, most of Latin America do not perform resistance assays before starting ARV treatment and after first line failure, having more resistance as a consequence in some cases and the need for more expensive salvage treatments. Some countries in the region do not have access to resistance tests due to cost and lack of infrastructure. The presentation will include data on the limited increase of transmitted resistance over time in the region compared to other developing countries, especially in Africa, as well as the prevalence of secondary resistance in first line failure and multiexperienced patients, with remark on specific issues with non-B subtypes. The elevated cross-resistance to the entire nucleoside analogue group in countries still using thymidine compounds in first line treatment will be stressed. Moreover, it will include the big limitations for resistance assay interpretations and performance in low level viraemia in Latin America as well as the excellent results of using resistance committees in the optimization of available assays as in the prescription of newer drugs. 10.7448/IAS.16.2.18693 © 2013 Soto-Ramirez L; licensee International AIDS Society Published 13 June 2013 Oral Abstracts Citing Literature Abstract Introduction Access to highly active antiretroviral therapy (ART) is expanding in resource limited settings (RLS), and ART regimens are frequently changed. Outcomes after changes in the first regimen (ART-1) have not been well studied in RLS. CCASAnet is a consortium of adult HIV clinics from seven countries (Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru). Methods Retrospective observational cohort study, assessing rates of death, virologic failure (VF), and change in second ART regimen (ART-2) after modification/changes of ART-1. Rates were computed using Kaplan-Meier methods and hazard ratios (HR)—adjusted for sex, age, CD4, clinical stage, calendar year, time between starting regimens, reasons for changing ART-1, and type of regimen change—were computed using Cox models stratified by site. Results A total of 3,384 patients (25% of total initiating HAART) changed ART-1 by at least one drug and were included in this study, with a median follow-up of 2.8 years from start of ART-2. Median age at start of ART-2 was 37 years, 60% were male, and median CD4 was 181 cells/µL; toxicity was the most common reason for changing ART-1 (48%) and the median time from start of ART-1 was 275 days. After starting ART-2, 319 patients (9.4%) died; the probability of death at years 1, 3, and 5 after ART-2 was 0.06, 0.10, and 0.12, respectively. Risk factors for death were older age (HR = 1.24 for 50 vs. 40 years; p = 0.052), clinical AIDS at first visit (HR 1.30; p=0.027), and lower CD4 at start of ART-2 (HR = 1.67 for 200 vs. 350 cells/µL; p<0.001). While on ART-2, 366 (18%) of patients experienced VF; the cumulative incidences of VF after 1, 3, and 5 years were 0.11, 0.22, and 0.28, respectively. Risk factors for virologic failure were younger age (HR = 1.41 for 20 vs. 40 years; p=0.003), lower CD4 (HR = 1.47 for 200 vs. 350 cells/µL; p<0.001), starting ART in an earlier year (HR = 1.20 for 2004 vs. 2007; p=0.006), and changing to ART-2 due to failure (HR = 2.05 compared to toxicity; p<0.001) or for some other non-toxicity reason (HR = 1.57; p=0.001). The cumulative incidence of changing ART-2 after 1, 3, and 5 years was 0.30, 0.51, and 0.64 respectively. Conclusions In a multi-centre resource-limited setting cohort of patients modifying their first ART regimen, rates of subsequent ART regimen modifications, mortality, and virologic failure were high. Access to expanded ART formularies, especially with newer, safer-profile drugs, is needed. 10.7448/IAS.16.2.18666 © 2013 Wolff M et al; licensee International AIDS Society Published 13 June 2013 Oral Abstracts Citing Literature Abstract Introduction Third-line antiretroviral drugs (ARV) are now indicated for the treatment of multi-resistant HIV/AIDS patients in virological treatment failure. Although being the last and highly effective line of defence, they are almost not present in the South because of their prohibitive cost. Therefore, Brazil, where these drugs have been adopted since 2005, constitutes an ideal laboratory to study next-generation drugs inclusion. Materials and methods Study the Brazilian Program focusing on costs of this new treatment strategy. We monitored the purchases between 2007 and 2009 looking for unitary costs of drugs and the total costs for the Ministry of Health. This research was based on the review of official documents from the Ministry of Health and statistical work on National Health Bank (BPS) and Ministry of Health budget databases. Results The National Program HIV/AIDS now distributes five third-line ARV: Darunavir (introduced in 2007), enfuvirtide (2005), etravirine (2010), raltegravir (2008), tipranavir (2010), all patented and imported at very high prices. Over time, however, a lower purchase price is observable (see Table 1). Thus, the price of darunavir (300 mg tablet) decreased by 19.6% between 2007 and 2009; enfuvirtide (108 mg vial) by 19.3% between 2007 and 2009; raltegravir (400 mg tablet) by 12.8% between 2008 and 2009. Table 1. Informations for third-line ARV in Brazil Total cost (dollar) Average annual price Daily dose price Quantity purchased Darunavir 300 mg tablet 2007 $ 11 357 243,05 $ 4,95 $ 19,81 2 293 200 2008 $ 16 768 434,62 $ 4,98 $ 19,92 3 366 490 2009 $ 51 648 122,75 $ 3,98 $ 15,94 5 659 680 Enfuvirtide 108 mg vial 2007 $ 24 836 274,11 $ 25,87 $ 51,74 960 000 2008 $ 61 612 677,02 $ 24,65 $ 49,31 2 499 000 2009 $ 27 234 536,44 $ 20,87 $ 41,74 1 305 000 Raltegravir 400 mg tablet 2008 $ 7 771 986,41 $ 10,65 $ 21,30 729 600 2009 $ 67 394 879,46 $ 9,29 $ 18,58 7 254 160 In 2008, only three third-line ARVs consumed together approximately 26% of the total budget for the acquisition and distribution of National HIV/AIDS Program (see graphic 1). In 2009, the situation becomes even more significant: almost 40% of the total budget were spent with these three ARVs (see graphic 2). Graphics 1 and 2. Total budget of acquisition and distribution of the National HIV/AIDS Programme (ARVs and other drugs). Source: Data from Brasil (2011b) and BPS (2011). Discussion and conclusion Brazil is considered a middle-income country and therefore cannot be benefited with the low prices offered to low-income countries. However, as ARVs purchases are performed centrally, we expected a greater bargaining power by the Ministry of Health. In practice, there are price reductions when increasing quantity purchases, but this does not seem sufficient to ensure financial sustainability of the rising third-line ARV Program. Today, third-line ARVs are distributed to 5,000 patients (from the universe of 190,000 patients that are currently receiving antiretroviral therapy) and consume 40% of the total ARV procurement. This scenario seems daunting given the strategies of ARV treatment, which already consumes two percent of the total ministerial budget. In fact, it is essential to continue negotiations with the pharmaceutical industry; furthermore, we must not forget the investment in infrastructure and human resources for national production. In the future, Brazil can be benefited by voluntary licenses granted by the patent-pool strategies, but it is necessary to be able to absorb the new technologies involved in the production of third-line drugs. 10.7448/IAS.16.2.18685 © 2013 Zaire C et al; licensee International AIDS Society Published 13 June 2013 Oral Abstracts O21–Hepatitis and HIV Citing Literature Abstract Although co-infection with both hepatitis B and hepatitis C in HIV is a common phenomenon, it should be remembered that the livers with those living with HIV are under attack from various other areas as well. These include the HIV virus itself which may infect stellate cells leading to the generation of fibrosis, antiretroviral therapy, other clinical medications, recreational drug use, other infections as well as traditional risk factors, principally alcohol. Approximately four million individuals are estimated to be co-infected with HIV and hepatitis B. Fortunately, there are agents which are active against both HIV and hepatitis B infection. The majority of individuals will have suppressed hepatitis B replication through receiving HAART containing tenofovir with either lamivudine or entricitabine. Alternative therapeutic options for individuals who are co-infected include pegylated interferon, entecavir, telbivudine and adefovir. Entecavir and telbivudine also have potential anti-HIV activity and therefore should only be administered with highly active antiviral therapy against HIV. Adefovir may be prescribed as monotherapy for hepatitis B alone, although it is less potent than other but at the dose utilised there is no activity against HIV. It is essential that all individuals with hepatitis B are monitored for the development of hepatoma due to an increased frequency of development and progression of this tumour type in those co-infected with hepatitis B. HIV and hepatitis C co-infection is common due to shared routes of transmission and similar geographical distributions. Although hepatitis C does not impact on the prognosis of HIV disease, HIV is associated with more rapid progression of fibrosis and hence hepatic complications associated with hepatitis C infection. Globally there is an epidemic of acute hepatitis C in HIV-infected homosexual men, which is fuelling the numbers who are co-infected. Hepatitis C infection is associated with complications associated with HIV disease including a higher risk of cardiovascular disease, diabetes, renal dysfunction, and osteoporosis with bone fractures. The development of the protease inhibitors telaprevir and boceprevir for the treatment of hepatitis C has translated into improvements in the outcome of therapy in the hepatitis C mono-infected population; although only small studies are available, the results in the co-infected population appear to be similar. In addition, second generation protease inhibitors have been associated with early response rates, even higher than with telaprevir and boceprevir in the co-infected populations. The generation of interferon-sparing regimens is also of great promise, and clinical studies have recently commenced in the HIV-infected population. It is essential that individuals with HIV are tested for hepatitis B and for hepatitis C and vice-a-versa, and that these are repeated frequently, so that individuals who are or do become co-infected can benefit from the positive outcomes associated with these new treatments. 10.7448/IAS.16.2.18694 © 2013 Nelson M; licensee International AIDS Society Published 13 June 2013 Oral Abstracts O21–Hepatitis and HIV Citing Literature Abstract Introduction Recently approved HCV protease inhibitors (PIs) have drug interaction liabilities with key HIV antiretrovirals (ARVs), specifically, ritonavir-boosted PIs. Sofosbuvir (SOF, formerly GS-7977), a NS5B nucleotide inhibitor, is in Phase 3 clinical development for the treatment of chronic HCV infection. We conducted a study to evaluate potential interactions between SOF and common HIV ARVs of varying 3rd agent classes (NNRTI, PI/r and integrase inhibitor-based). Methods In a Phase 1, fixed sequence, 4-cohort study, healthy volunteers received a single dose of SOF 400 mg before and after 14 days of Atripla (ATR, EFV/FTC/TDF 600/200/300 mg QD; n = 17, fasted), or 10 days of rilpivirine (RPV, 25 mg QD, n = 17, fed), darunavir/ritonavir (DRV/r, 800/100 mg QD, n = 19, fed), or raltegravir (RAL, 400 mg BID, n = 19, fasted). Geometric means ratio% (GMR%, combination vs alone) of PK parameters AUCinf and Cmax for SOF and GS-331007 (circulating nucleoside metabolite of SOF), or AUCtau, Cmax, and Ctau for TFV, FTC, EFV, RPV, DRV/r, or RAL were evaluated against a predetermined 70–143% equivalence boundary. Safety assessments were conducted throughout the study. Results A total of 16 and 17 subjects completed the ATR and RPV cohorts, respectively, and 18 subjects completed the DRV/r and RAL cohorts. The most frequent adverse events were dizziness, headache, diarrhea, nausea, and constipation, predominantly during ATR dosing. All but one event were mild and most were consistent with known EFV adverse events. Overall, SOF was well tolerated with very few treatment-emergent events during the administration of SOF with ARVs. Co-administration of HIV ARVs and SOF did not result in clinically significant changes in SOF and/or GS-331007 exposure. ATR slightly decreased SOF and GS-331007 Cmax (~20–23%), RPV, DRV/r, and RAL modestly increased SOF exposure by 21 to 45% with no effect on GS-331007. SOF slightly increased TFV Cmax (~25%), modestly decreased RAL AUCtau (~27%) and Cmax (~43%), but did not affect RAL Ctau, and had no other effect on PK parameters of FTC, TFV, EFV, RPV, or DRV/r. Conclusions No clinically significant DDIs were observed between SOF and EFV, RPV, DRV/r, RAL or the standard-of-care backbone of FTC/TDF. These data support potential use of SOF with a variety of ARV regimens in the HIV/HCV co-infected population. 10.7448/IAS.16.2.18678 © 2013 Kirby B et al; licensee International AIDS Society Published 13 June 2013 Oral Abstracts O22 - Living Longer with Haart and Non-Communicable Diseases and HIV Citing Literature Abstract Life expectancy (LE) is an important indicator of health used widely by government and healthcare agencies to monitor trends over time and to determine resource allocation, as well as by insurance companies and pension providers. LE of the HIV-positive population has increased dramatically since the introduction of combination antiretroviral therapy (cART); indeed, it is now believed that LE may be similar to that of the general population in some subgroups. There are, however, specific subgroups in which LE remains substantially impaired. The impact of HIV and of cART on mortality may be expressed in several ways. LE itself provides an estimate of the average additional number of years that an individual would be expected to live beyond a particular age. However, the detrimental impact of HIV may also be described in terms of the number of years of life lost or the gains in LE if HIV were to be eliminated as a cause of morbidity in the population. My presentation will start with a description of the different methods that researchers have used to describe the mortality outcomes of those with HIV, and the impact of cART on these. I will then consider how LE in the HIV-positive population has changed over time, and will describe the impact of demographic factors (e.g., gender, age, ethnic group) on LE. To investigate