To Be Or Not To Be? Daily Oral Versus Long-Acting Injectable Medicines For HIV Prevention

Scientific research has gifted us with a range of evidence-based options to protect ourselves from getting infected with HIV. In 2012, US FDA had first approved Pre-Exposure Prophylaxis (PrEP) daily oral medicines for HIV prevention. More recently, long-acting injectable options of PrEP are also approved. We at CNS listened to the experts on both of these PrEP options so that we can make an informed choice.

A lively debate was organised at the recently concluded 10th Asia Pacific AIDS and Co-Infections Conference (APACC 2025) in Tokyo, Japan, on "Should Long-Acting Injectables (LAIs) Replace Oral Antiretrovirals for Biomedical HIV Prevention in the Asia-Pacific Region?" Also, 13th International AIDS Society Conference on HIV Science (IAS 2025) and 2nd Asia Pacific Conference on Point-of-Care Diagnostics for Infectious Diseases (POC25) will open soon.

Arguments in favour of long-acting injectable PrEP dwelt upon the current dismally low use of oral PrEP in the Asia Pacific Region - as of end 2023, around 204,000 individuals were actively using PrEP - just 2% of the 8.2 million target set for 2025. Also a significant number of individuals discontinue PrEP within a relatively short period of time after initiation. For example, in Thailand, a programme serving over half of all PrEP users, saw 47% of clients discontinuing within 12 months, according to the Institute of HIV Research and Innovation (IHRI).

"I don't fear the side effects. I fear the side eyes"

Varied reasons were put forward by debater Jennifer Ho, a global health advocate from Thailand, included "Oral PrEP is not reaching those most at risk. Transgender women navigating stigma in clinics, sex workers who cannot safely carry pills; men who have sex with men and young men hiding their PrEP from family; persons who use drugs facing criminalisation - all of these find it difficult to take daily oral PrEP. Pill shaming keeps people from starting or leads them to quietly stop, because of 'I don't fear the side effects. I fear the side eyes.' On the other hand, long-acting injectables remove structural and behavioural barriers and can reach people outside formal systems. We need prevention tools that meet people's needs. Prevention works when it does not depend upon disclosure, disability or perfect routine. Oral PrEP stigmatises life because you have to take a pill daily. Long-acting injectables are discreet, there is no daily pill to remember, there is no need to hide. Long-acting injectables are a prevention strategy that is realistic, respectful and responsive."

Dr Nagalingeswaran Kumarasamy, a well known infectious disease expert from India gave a doctor’s perspective on the necessity of long-acting injectable PrEP. He serves as Chief and Director of Infectious Diseases Medical Centre at Voluntary Health Services Hospital in Chennai, India. He is also the Secretary General of AIDS Society of India (ASI) - a nationwide network of medical experts and researchers on HIV, co-infections and co-morbidities.

Dr Kumarasamy said that daily PrEP pill is not a suitable or desirable prevention strategy for everyone. We need more options as well as expanded access or use by key populations (people who are at a heightened risk of HIV). Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives. Cost effectiveness is different from cost of sale. Long-acting injectables will be cost effective in the long run. It is too much to expect daily adherence from people who are not sick. Also studies have found that long-acting injectables like cabotagravir and lenacapavir to be superior to oral PrEP.

It is not about 'either/or' but expanding options for HIV prevention

While conceding that long-acting injectable PrEP is promising, Danvic Rosadiño, Co-Chair, WHO Guidelines Development Group on Long-acting Injectable Cabotegravir for HIV Prevention, firmly argued that replacing oral PrEP is premature, impractical and inequitable. Danvic heads programmes and innovations at LoveYourself in the Philippines.

"It is not a question of ‘either’, ‘or’. It is about expanding options, and not eliminating them. In a socially, economically and politically diverse region like the Asia Pacific, this will risk undermining progress. The three core reasons why oral PrEP should not be replaced is cost, convenience and confidence," he said.

"Long-acting injectable PrEP is far more expensive than generic oral PrEP. How many governments of this region will be able to afford long-acting injectables? If we replace oral PrEP, we will be leaving the most vulnerable behind. We have been able to roll out PrEP in a very de-medicalised manner. We have built our systems which allow oral PrEP to be accessed in community clinics, in mobile clinics, in peer outreach facilities. It is easy, discreet and empowering, especially for those avoiding judgmental or stigmatising healthcare settings. However long-acting injectables might bring us to clinical dependence, and many of our clients do not feel welcome in clinical facilities. We set up communities for giving oral PrEP because the mainstream system was not built for us. It excluded and stigmatised the community. We have created alternate spaces where people could feel safe, respected and seen not just as patients but as people. If we shift HIV prevention back to clinical systems, we risk destroying those safe spaces. Long-acting injectables might require clients to go back to those places which they actively avoided. Granted that long-acting injectables are very promising, replacing oral PrEP with them would create barriers and not bridges. We must protect choice. Different people need different things-some will prefer pills, some will prefer injectables. Let us invest in building a system where these options co-exist and where everyone- no matter where they live - can access HIV prevention that works for them," said Danvic.

Do not forget stigma, inequity and costs

Dr Rayner Kay Jin Tan, an Assistant Professor at the Saw Swee Hock School of Public Health, National University of Singapore, supported Danvic. He opined that “Stigma, inequity and costs are very important considerations when we think about PrEP and other HIV prevention products. Keeping these things in mind, we should not replace oral PrEP with long-acting injectables. Oral PrEP has been de-medicalised to a large extent and distribution is community driven, thus bringing access to communities. And the cost of long-acting injectables is still not known. No generic manufacturer has given any idea of what it would cost. And most of the HIV infections are in countries that will not be able to meet the high cost of long-acting injectables. Except for Australia, no other countries in the Asia-Pacific have approved any long-acting injectable PrEP.

However, both sides agreed that not everyone needs the same prevention options, but everyone deserves what works best for them. Speed, scale, implementation, and equity must be at the core of translating exciting scientific tools into public health impact.

Give real choices to people to choose from full range of HIV combination prevention options

It is now for the readers to decide which premise do they support- long-acting injectables or daily oral PrEP -till science develops more exciting HIV prevention tools. And above all, expanding the range of prevention options to protect ourselves from HIV should always remain the mainstay - and trusting people to have real choices if all combination prevention options are offered to them.

Oral PrEP or pre-exposure prophylaxis is an HIV medicine taken daily by HIV negative individuals that reduces their risk of acquiring HIV through sex by about 99% and from injection drug use by at least 74%. PrEP should be used with condoms when possible. There are newer approved PrEP options that also protect us against few STIs, like Doxy PrEP (which provides reasonable protection against getting infected with STIs like syphilis, chlamydia, and gonorrhoea).

Know more about long-acting injectable PrEP

Since 2022, one of the long-acting injectable PrEP has a medicine called cabotegravir which has shown high efficacy in protecting us from HIV. It involves injections administered intramuscularly, with the first two injections given four weeks apart, followed thereafter by an injection every 8 weeks.

Studies have shown it to be safe and superior to daily oral PrEP (which uses medicines like tenofovir and emtricitabine) for HIV prevention among cisgender women, cisgender men who have sex with men, and transgender women who have sex with men. It offers a promising alternative to daily oral PrEP, particularly for individuals who may face challenges with adherence to daily medication. It was recommended by the WHO in 2022 as an additional HIV prevention option for people at substantial risk of HIV infection.

However, its current high cost of US$ 22,000 per year per user jeopardises its potential for public health benefits. In July 2022, its manufacturer ViiV Healthcare announced a voluntary license with the Medicines Patent Pool, allowing 90 countries to buy generic versions of cabotegravir for HIV prevention. The cost of generic version is expected to be potentially around US$ 16-34 per person per year. However, generic versions will not be out before 2027.

Long-acting Lenacapavir

Long-acting lenacapavir PrEP given as a subcutaneous injection once every 6 months, has been found to be highly effective. In 2024, two landmark clinical studies- PURPOSE 1 and PURPOSE 2- showed it to be 100% efficacious in preventing HIV among cisgender women and 96% efficacious among men who have sex with men, transgender and gender non-binary individuals, and was found superior to oral PrEP.

It is currently priced at US$ 42,250 per year per person in the US, but is expected to become much more affordable to around US$ 200-300 per year per person with the introduction of generic versions, that are expected to be available by 2027.

Shobha Shukla – CNS (Citizen News Service)

(Shobha Shukla is the award-winning founding Managing Editor and Executive Director of CNS (Citizen News Service) and is a feminist, health and development justice advocate. She is a former senior Physics faculty of prestigious Loreto Convent College and current Coordinator of Asia Pacific Regional Media Alliance for Health and Development (APCAT Media) and Chairperson of Global AMR Media Alliance (GAMA received AMR One Health Emerging Leaders and Outstanding Talents Award 2024). She also coordinates SHE & Rights initiative (Sexual health with equity & rights).

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