Is long-acting HIV treatment as good as taking daily pills ?

Bobby Ramakant *

Dr Jurgen Kurt Rockstroh, University Hospital Bonn, Germany

Treatment for people living with HIV (antiretroviral therapy) is lifesaving and revolutionary as it has made HIV akin to any other chronic disease. It has been proven that those who are on treatment and remain virally suppressed, live healthy and normal lifespans - comparable to those without the virus – and there is zero risk of any further HIV transmission from them.

But oral HIV treatment has to be taken daily without fail. This could be challenging given the fact that HIV treatment is lifelong.

Recently, long-acting injectable treatment options have been proven to be as effective as the daily oral therapy. However, a very small number of those on long-acting options reported virological failure (and higher risk of HIV virus developing resistance against HIV medicine, also referred to as drug-resistance or antimicrobial resistance/AMR).

But is the long-acting therapy for everyone?

A lot of such questions were answered by Dr Jurgen Kurt Rockstroh, Head of Infectious Diseases, Department of Medicine, University Hospital Bonn in Germany. Dr Jurgen has earlier served as the Chairperson of German AIDS Society, and President of European AIDS Clinical Society (EACS) too. He gave a plenary talk at the 16th National Conference of AIDS Society of India (ASICON 2025) in Ahmedabad, India. Dr Jurgen was conferred upon the ASI Lifetime Achievement Award by the Chief Minister of Gujarat Bhupendra Patel and Dr Ishwar Gilada, Emeritus President, ASI and Governing Council member of International AIDS Society (IAS).

Antiretroviral therapy is lifesaving, revolutionised HIV care

Dr Jurgen said that over 95% of people who are diagnosed positive for HIV and initiated on first-line oral antiretroviral therapy soon achieve viral suppression with undetectable viral load. “An overwhelming body of clinical evidence has firmly established that undetectable HIV viral load means that HIV is untransmittable from these people, which is often referred to as undetectable equals untransmittable or U equals U/ U=U).”

Dr Jurgen added that “near to normal life expectancy for people living with HIV is a reality now if antiretroviral therapy is started early enough and the person stays virally suppressed.” He pointed out that in the rare event of HIV virological failure, there is a risk for drug-resistance development. Less than 2% people who are on antiretroviral therapy discontinue due to adverse events.

If all is good, then why do we need new options?

Yes, HIV treatment – daily oral regimen – is lifesaving and good – access to which is critically important in a rights-based manner for all those with HIV. However, there could be people who might find it difficult to take daily pills or those who want more choices of long-acting options.

Those people with HIV who are unable to adhere to daily oral therapy or face HIV-related stigma and risk of discrimination (for example, 40% of people in a multi-country study said that they fear that their HIV medicines would be found by others and lead to HIV disclosure, stigma and discrimination), or those who are struggling with treatment fatigue of a lifelong therapy or wish for treatment simplification, or those who do not want to be reminded of having HIV every day – day after day (35% of study participants in a multi-country study said this was a concern for them), or those who have difficulties in swallowing pills, are the ones who may consider long-acting treatment options.

Dr Jurgen shared an example of a person who opted for long-acting regimens: a woman living with HIV who is a native of one of the African nations and under his medical care in Germany, has a HIV negative child. She did not want to disclose or risk disclosing her HIV status to her child as she lives in a community-setting where HIV disclosure could mean being forced out of the group. So, it was important for her to ensure that others may not find her medicines. That is why, she opted for long-acting therapy and continues to remain virally suppressed and healthy.

A study published in 2018 gauged interest in potential new ARV therapies back then among 263 people with HIV from clinics in Duke and University of South Carolina. Four-fifths of these study participants came from racial and ethnic minorities, 89% were virally suppressed and, on an average, they were on antiretroviral therapy for around twelve years.

In the study, two-thirds of the respondents (61%) said yes to the choice of "taking a single pill once a week," followed by one-thirds of those (34%) who opted for 2 injectables given in a clinic setting every two months. Lowest interest was towards 2 plastic implants in the forearm every six months as a mode of administering the therapy.

Choice matters

Dr Jurgen Rockstroh said that “Increased flexibility of delivery of antiretroviral therapy is needed to meet the diverse needs of people living with HIV. People continue to face physical, emotional, and psychological challenges with daily oral therapy. These challenges have been associated with poor health outcomes, including low treatment satisfaction, self-reported virological failure, suboptimal self-rated overall health, and poor adherence.”

What is long-acting HIV treatment?

Studies have shown that long-acting injectable HIV treatment regimens of cabotegravir and rilpivirine (intramuscular injection once every month or every two months) are as effective as daily oral regimens. Those people who may find it difficult to adhere to a daily oral therapy or confront HIV disclosure or stigma, may opt for long-acting ones if found eligible. Long-acting regimens are recommended as a preferred option for those people with HIV who are virologically suppressed or those who are on a stable antiretroviral regimen and might be facing challenges with daily oral therapy.

Long-acting regimens are now recommended by several HIV treatment guidelines, including those of US Department of Health and Human Services, EACS, and International Antiviral Society USA, among others.

There are new options of administering long-acting antiretroviral medicines, two of which are:
- Intramuscular injections of cabotegravir and rilpivirine medicines once every two months
- Sub-cutaneous injections of lenacapavir once every six months

Dr Jurgen pointed out that taking intramuscular injections could be a bit challenging as it could be painful and not easy for everyone. Comparatively, subcutaneous injections could be a little easier in this respect.

He said that when supported by intensive follow-up and case management services, injectable cabotegravir and rilpivirine may be considered for people who otherwise meet the criteria - such as, unable to take oral therapy, high risk of HIV disease progression with CD4 below 200 or history of AIDS defining complications, and the virus which is susceptible to both cabotegravir and rilpivirine medicines.

Long-acting injectable antiretroviral therapy options expand the number of choices for those who may be struggling to overcome HIV-related stigma or struggle with HIV disclosure but "there is an existent risk of virological failure even in fully adherent individuals, and virological failure is associated with higher risk of drug-resistance development," said Dr Jurgen.

As more scientific evidence and lessons from the roll-out of long-acting options come forth, we need to ensure that every person living with HIV is able to access the latest regimens of lifesaving antiretroviral therapy - and all choices of treatment delivery options are available and accessible to those who are eligible for them.