Oral anti-retroviral therapy (ART) has been used in the treatment of HIV since the early 1990s. Recently, scientists have been working to develop long-acting methods of treatment and prevention of HIV. Oral treatment currently consists of a three-drug therapy which is sometimes combined to create a one pill, once-a-day regimen. When taken as prescribed, these drugs can suppress the viral load of a person living with HIV. Adequate suppression of viral load results in the virus being untransmittable (1). This means a person living with HIV on adequate treatment cannot pass the virus to another person. Pre-exposure prophylaxis (PrEP) is ART given to an uninfected person who is at risk of HIV infection. In Scotland, PrEP is available through the NHS and more information about eligibility can be found at https://prep.scot/.

A key factor in successful HIV treatment and prevention is adherence to a medication regimen. This means a person must take the treatment as it is prescribed by a healthcare professional and not miss any doses. Doing this allows the drug to work effectively to suppress a person’s viral load. Not adhering to a treatment regimen as it is prescribed or missing doses makes it more likely that the virus will develop resistance to a drug, meaning that that drug may no longer work. There are many reasons why a person may not be able to adhere to a treatment or prevention regimen. These include: experience of side effects; interactions with other medications which a person may be taking; difficulties in accessing services which provide treatment; pill fatigue; and the stigma associated with HIV (2).  Pill fatigue is common in people living with chronic conditions which require everyday medication therapy and is reported by some living with HIV (3).

Long-acting therapies have revolutionised contraception, particularly in low and middle-income countries. In some countries in Sub-Saharan Africa, 60-80% of women on contraception are on long-acting therapies (2,4). For many, these increase adherence and make it less likely that they miss a dose. Since this is a key factor in successful viral load suppression in HIV treatment, it is hoped that long-acting therapy would increase treatment success. Most importantly, long-acting therapies may be preferred by people living with HIV or at risk of HIV infection. A US study found that over 80% of survey respondents would definitely or probably consider switching from oral therapy to parenteral (non-oral) therapy where injection frequency would be once per month; interest decreased as injection frequency increased (5). People living with HIV participating in current trials of long-acting therapies reported benefits such as: increased convenience and flexibility, reduction in daily reminder of HIV status and an alternative route for those who cannot take oral medication (6).

The progress of research into long-acting injectable treatment and preventative therapies was presented at the AIDS2020 conference. For the treatment of HIV, the FLAIR, ATLAS and ATLAS-2M trials have shown success in treating patients with 4 and 8 weekly injections of ART (7–9) . As well as this, long-acting injectable PrEP has shown to be as effective as oral PrEP in men who have sex with men and transgender women in clinical trials (10).

As with every medication, there are factors which might make an injectable method less suitable for some. Since these drugs are long-acting, they will stick around in the body for longer. This means if a person experiences side effects, it will be more difficult to stop the drug compared to an oral form (although the drugs being trialled are generally well-tolerated: cabotegravir and rilpivirine). Additionally, this may cause problems with drug resistance as concentrations begin to decrease in the body if a person misses a dose or stops therapy. Adherence to injectable treatment regimen would be as important as it is for an oral regimen. Researchers are aware of these challenges and are working to overcome them (2). As well as this, a person may find the injection painful and may experience injection site reactions. However, participants of the ATLAS and FLAIR trials found this to be ‘very acceptable’ or ‘totally acceptable’ and reported a higher degree of treatment satisfaction with long-acting methods (6). Ultimately, different regimens work for different people. Research is also underway to create alternatives to oral and injectable methods of treatment and prevention. These include implants which are placed under the skin, patches placed on the skin and vaginal rings, similar to current contraceptive devices (2,11). This would potentially overcome some of the challenges of long-acting injectable medications as they could be removed from the body if no longer suitable for a person. For example, because of side effects, pregnancy or interactions with other medication a person is taking.

As a medical student, I was really excited to hear about the trials of long-acting medication. Throughout university, I have learnt about the importance of choice when living with a health condition and think that every person should have a choice of treatment where possible, allowing them to have the best quality of life. Each individual’s needs are different with different things which are important to them in managing their health and health conditions. Giving people choice and continuing to research and develop drugs which suit the needs of people living with HIV supports this and is essential in delivering person-centred healthcare. I hope that we continue to ask and respond to the needs of people living with HIV in healthcare and in our wider society. I believe this is key to ensuring progress in treating and managing HIV and ensuring people live well.

@SophieCorbett

References:

  1. WHO | Viral suppression for HIV treatment success and prevention of sexual transmission of HIV [Internet]. WHO. World Health Organization; [cited 2020 Aug 6]. Available from: http://www.who.int/hiv/mediacentre/news/viral-supression-hiv-transmission/en/
  2. Gulick RM, Flexner C. Long-Acting HIV Drugs for Treatment and Prevention. Annual Review of Medicine. 2019;70(1):137–50.
  3. Claborn KR, Meier E, Miller MB, Leffingwell TR. A Systematic Review of Treatment Fatigue among HIV-infected Patients Prescribed Antiretroviral Therapy. Psychol Health Med. 2015 Apr;20(3):255–65.
  4. Rattan J, Noznesky E, Curry DW, Galavotti C, Hwang S, Rodriguez M. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo. Glob Health Sci Pract. 2016 Aug 11;4(Suppl 2):S5–20.
  5. Williams J, Sayles HR, Meza JL, Sayre P, Sandkovsky U, Gendelman HE, et al. Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients. Nanomedicine (Lond). 2013 Nov;8(11):1807–13.
  6. Murray M, Antela A, Mills A, Huang J, Jäger H, Bernal E, et al. Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks. AIDS Behav [Internet]. 2020 May 23 [cited 2020 Aug 6]; Available from: https://doi.org/10.1007/s10461-020-02929-8
  7. ViiV Healthcare reports positive 48-week results for first pivotal, phase III study for novel, long-acting, injectable HIV-treatment regimen [Internet]. [cited 2020 Aug 6]. Available from: https://viivhealthcare.com/en-us/us-news/us-articles/2016/viiv-healthcare-reports-positive-48-week-results-for-first-pivotal-phase-iii-study-for-novel-long-acting-injectable-hiv-treatment-regimen/
  8. ViiV Healthcare presents positive, 48-week data from phase III study showing every-two-month regimen of investigational long-acting, injectable cabotegravir and rilpivirine has similar efficacy to once-monthly dosing [Internet]. [cited 2020 Aug 6]. Available from: https://viivhealthcare.com/en-gb/media/press-releases/2020/march/viiv-healthcare-presents-positive--48-week-data-from-phase-iii-s/
  9. ViiV Healthcare presents positive long-term data from phase III study demonstrating efficacy and safety of cabotegravir and rilpivirine, its investigational, long-acting HIV-treatment regimen in adults living with HIV-1 [Internet]. [cited 2020 Aug 6]. Available from: https://viivhealthcare.com/en-gb/media/press-releases/2020/march/viiv-healthcare-presents-positive-long-term-data-from-phase-iii-/
  10. Exciting new results from long-acting PrEP study show it to be effective in preventing HIV acquisition in men who have sex with men and transgender women [Internet]. [cited 2020 Aug 6]. Available from: https://www.who.int/news-room/detail/20-05-2020-exciting-new-results-from-long-acting-prep-study-show-it-to-be-effective-in-preventing-hiv-acquisition-in-msm-and-transgender-women
  11. Vaginal ring for HIV prevention receives positive opinion from European regulator [Internet]. National Institutes of Health (NIH). 2020 [cited 2020 Aug 6]. Available from: https://www.nih.gov/news-events/news-releases/vaginal-ring-hiv-prevention-receives-positive-opinion-european-regulator