Future of HIV Management

Ask the Expert: Aadia Rana, MD, on the Future of HIV Management

Take Note

• Antiretroviral therapy (ART) will continue to become safer and better-tolerated, with more choices among fixed-dose combination single-tablet regimens and the development of long-acting injectables that may allow patients to receive treatment once every 1-2 months.
• As patients live longer with HIV, the emergence of non-AIDS-related conditions increases the role of primary care physicians in monitoring for metabolic complications such as cardiovascular disease and kidney problems.
• HIV prevention has undergone dramatic advances in recent years with the advent of treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP).

Management of human immunodeficiency virus (HIV) infection has long been a rapidly evolving field, with incremental but important changes in the approach to testing, treatment, and prevention. Aadia Rana, MD, Assistant Professor of Medicine at the Warren Alpert Medical School of Brown University, recently sat down with MedPage Today to share her insights into the future of HIV management. Dr. Rana cares for patients as an internal medicine and infectious disease physician at Miriam Hospital and Rhode Island Hospital, major teaching affiliates of the Warren Alpert Medical School in Providence. She completed a combined clinical and research fellowship in infectious diseases and HIV Health Services Research.
MedPage Today: What is the future of antiretroviral therapy (ART)?
Dr. Rana: In the immediate future, we are seeing further development and release of better-tolerated fixed-dose combination therapies (1 pill-once-a day). Just this past month, a new formulation of tenofovir disoproxil fumarate (TDF), known as tenofovir alafenamide, was approved by the Food and Drug Administration (FDA) as part of a fixed dose combination with emtricitabine-cobicistat-elvitegravir. Tenofovir alafenamide has been shown to have less of an impact on kidney and bones compared with TDF.¹
Additionally, there is research underway on the use of long acting injectable antiretroviral therapy where, after some time on oral therapy with adequate response, patients may be able to remain on maintenance therapy with antiretroviral injections either monthly or every 2 months.
Overall, the new United States (US) Department of Health and Human Services (DHHS) April 2015 HIV treatment guidelines are revolutionary in that they now recommend 5 initial regimens: 4 integrase inhibitor-based regimens (including 2 fixed-dose combinations) and only 1 boosted protease inhibitor-based regimen. The gold standard NNRTI-based fixed-dose combination (still recommended in all other nations) is no longer a recommended regimen, in part because of inferiority to newer regimens, with increased risk of side effects and toxicity.
MPT: What is the future of primary care beyond ART for people living with HIV?
Dr. Rana: Over the past two decades, ART has radically altered the natural history of HIV infection. More than 50 percent of deaths in HIV-infected patients receiving ART are now related to conditions other than AIDS.² HIV infection appears to increase the risk of non-AIDS–related cardiovascular disease, renal disease, liver disease, and malignancies. Data from a recent study showed a 39% reduction of non-AIDS related conditions in those started on antiretroviral therapy with high CD4 counts (>500) compared with those who waited until the CD4<350.³
The emergence of non-AIDS-related conditions highlights the important role of the primary care physician in ensuring patients are monitored regularly for metabolic complications such as cardiovascular disease and kidney problems. Particularly, one must mention the recent developments in hepatitis C treatment that will significantly impact co-infected patients, as liver disease contributes to substantial morbidity and mortality among HIV-infected patients.
MPT: What is the future of HIV testing?
Dr. Rana: Continuing to remove barriers to HIV testing by modifying policies, addressing stigma, and improving outreach to hard to reach populations remains a top priority for HIV prevention researchers and policy makers. This will require continued collaboration among policy makers and researchers on implementing these strategies to ensure that individuals have access to rapid HIV testing in an accessible and comfortable environment, as well as corresponding immediate access to care and treatment.
MPT: What is the future of HIV prevention?
Dr. Rana: HIV prevention has undergone dramatic advances in recent years with two new prevention strategies: first, treatment as prevention (TasP); and second, pre-exposure prophylaxis (PrEP). TasP is the idea that HIV-positive people on ART with viral suppression are highly unlikely to transmit virus, so early treatment not only benefit the individual being treated, but also limits the spread of infection to other people.⁴
PrEP has been shown to be highly effective in randomized clinical trials (such as the PARTNERS PrEP study⁵) and in observational cohorts (such as the PROUD⁶and IPERGAY⁷ studies). There are also additional studies in development using potentially new agents for PrEP such as a long acting injectable antiretrovirals.
MPT: How do you think policy initiatives like the UNAIDS 90-90-90 initiative or the National HIV/AIDS Strategy in the US will impact the future of HIV testing, treatment, and prevention?
Dr. Rana: Both strategies have the potential to significantly impact the HIV epidemic nationally and internationally by highlighting awareness as well as creating benchmarks that can be tracked by health departments as well as members of the community. The UNAIDS 90-90-90 initiative issued at last year’s United Nations (UN) General Assembly were the UNAIDS targets for 2020 (the so-called 90/90/90 goals), aiming for 90% of HIV-positive people to know their status; 90% of those aware of their status to be on treatment, and 90% of those on treatment to be virally suppressed. Achieving these goals would result in an approximate doubling of people aware of their HIV status and a doubling of the number of people receiving treatment, which would considerably reduce rates of transmission globally. This initiative has already engaged over 30 cities on 5 continents to achieve 90/90/90 targets by the end of 2030. It is expected these cities will report on their progress at least annually, and cities are encouraged to produce quarterly internal reports and make them available to local stakeholders, particularly affected communities. So we should know relatively quickly what kind of progress we are making on the goals and gain insights on which strategies are working and which may need some adjustment to make them more successful.
With Michael Broder, PhD

Published: 12/21/2015
References:

1. Sax PE, Saag MS, Yin MT, et al. Renal and bone safety of tenofovir alafenamide vs tenofovir disoproxil fumarate. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 143LB.
2. Mocroft A, Brettle R, Kirk O, et al. Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study. AIDS. 2002 Aug 16;16(12):1663-71.
3. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. doi: 10.1056/NEJMoa1506816. Epub 2015 Jul 20.
4. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.
5. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399-410. doi: 10.1056/NEJMoa1108524. Epub 2012 Jul 11.
6. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2015 Sep 9. pii: S0140-6736(15)00056-2. doi: 10.1016/S0140-6736(15)00056-2. [Epub ahead of print]
7. Molina J-M, Capitant C, Spire B, et al. On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 23LB.