Modelling study finds benefits to widening PEP access but it's unclear how to implement it
Making the commonly prescribed antiretroviral regimen of tenofovir, lamivudine and dolutegravir available in the community as post-exposure prophylaxis after condomless sex, without a prescription, would reduce HIV acquisition by 31% over 20 years in African countries, according to a modelling study published in Lancet Global Health. Post-exposure prophylaxis (PEP) is the use of antiretroviral drugs after condomless sex to prevent HIV exposure, ideally started within 24 hours and continued for one month. PEP consists of a three-drug combination.
PEP is not available in community settings in eastern and southern Africa. A recent legal ruling allows South African pharmacists registered with a government scheme to provide PrEP or PEP without a prescription, but this remains unusual in the region. Wider community distribution, using the kind of methods employed to distribute condoms and HIV self-tests, has never been tried. Lack of awareness of PEP guidelines among healthcare providers, stigmatising attitudes among healthcare providers towards people in need of PEP, lack of community awareness of PEP and lack of availability outside health facilities are common obstacles to wider PEP uptake.
In the United States, pharmacies in 12 states are permitted to provide a 7-day supply of PEP without a prescription but prescribing laws in others states create barriers to easy PEP access.
Outside the United States, community access to PEP without a prescription is rare and the potential impact of community access to PEP on HIV transmission is uncertain.
To investigate the potential impact of community access to PEP in settings with high and medium HIV prevalence, the HIV Modelling Consortium used the HIV Synthesis model to assess the effects of making tenofovir, lamivudine and dolutegravir available as PEP without a prescription. This regimen was chosen because it is the preferred first-line treatment regimen in most countries in Africa and so the medicines supply system already has the capacity to supply it at scale.
The model compared the impact on HIV incidence and cost-effectiveness of current PrEP policies to the continuation of those policies with the addition of community TLD as PEP. Under current policies, PrEP consists of tenofovir/emtricitabine, long-acting injectable cabotegravir PrEP will be provided when it becomes available, and uptake of PEP is negligible. The model used data from 11 countries in east, central, west and southern Africa to calibrate HIV prevalence and incidence, the proportions diagnosed, on treatment and virally suppressed and the prevalence of unsuppressed HIV among adults.
The model assumed:
PrEP was only used in any three-month period if a person had condomless sex during that period or if the primary partner had unsuppressed HIV.
People would have varying willingness to take the two types of PrEP and varying ability to access services providing PrEP.
Oral or injectable PrEP had an efficacy of 90%-95% and TLD used as PEP had an efficacy of 90%.
TLD would in practice also be used as PrEP by a proportion of people, depending on the frequency of condomless sex.
The modelling showed that over three years, if community TLD was available:
25% of people in need of PEP or PrEP would take it without community TLD, compared to 35% if TLD were available.
Overall, the proportion of HIV-negative people taking PrEP or PEP would increase by 0.5% to 1.6%.
The proportion of people on PrEP who used injectable cabotegravir would fall from 35% to 29%.
The proportion of people with HIV on antiretroviral treatment would rise slightly, by 3% in men and 2% in women.
Over 20 years, HIV incidence would decline by 31% if community TLD was available and HIV prevalence would fall by 27%. The proportion of people with HIV on antiretroviral treatment would increase by 3% and deaths from AIDS would fall by 9%. No increase in the prevalence of resistance to integrase inhibitors or nucleoside/nucleotide reverse transcriptase inhibitors would occur.
Community TLD would save $18 million a year in antiretroviral treatment costs averted over 20 years and was cost-effective in 90% of the scenarios modelled.
Unanswered questions about community TLD
Although the modelling analysis shows that community PEP would be cost effective, it has never been tested as an intervention and there are numerous questions about its feasibility, acceptability and potential drawbacks.
The researchers acknowledge that there is a risk that people who have acquired HIV will start taking TLD without testing for HIV, posing a risk of treatment interruption and, in people with advanced HIV or TB, a risk of immune restoration inflammatory syndrome (IRIS). Although they tried to factor these problems into their model, the likelihood of these events occurring can only be assessed in implementation studies.
The researchers say that pilot implementation studies should be carried out to investigate community distribution. They suggest that PEP packs could be made available in the same way as condoms in public places so that people do not have to approach others for it.
The main barriers to access are regulatory, they acknowledge. In South Africa for example, private medical practitioners took legal action to block pharmacists from prescribing antiretrovirals for treatment or prevention. South Africa’s High Court rejected their case.
Use of PEP requires awareness of an HIV risk, but in a Comment accompanying the article, Dr Linda Stranix-Chibanda and Tsungai Mhembere of the University of Zimbabwe say that community TLD PEP would transfer the decision about whether to use antiretrovirals for prevention from prescribers to the person having condomless sex. This might enable a group of people not currently in contact with HIV services to access a highly effective prevention method.
Furthermore, “community TLD might shift the focus to groups that have disproportionately high HIV acquisition and transmission and extend the utility of currently available drugs before long-acting treatment and prevention becomes available.”
Community TLD might also affect demand for other prevention services, they suggest.
“Of particular interest is how people using community TLD would interact with HIV self-testing kits, and whether the approach would create new opportunities for expanding access to combination self-testing kits for HIV and other sexually transmitted infections,” say the Zimbabwean researchers.
But they warn that more insights are needed into the needs and motivations of people who use PEP and PrEP before developing pilot projects. “Respectful community consultations should formulate the proof-of-concept pilot projects, driving the communication strategy and implementation approach, to have the best shot at community TLD becoming a transformative and sustainable HIV response,” they advise.
References Phillips AN et al. Potential cost-effectiveness of community availability of tenofovir, lamivudine and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis. Lancet Global Health, 11: e1648-e1657, 2023. Published online 19 September 2023. Stranix-Chibanda L, Mhembere T. Unrestricted access to tenofovir, lamivudine and dolutegravir as pre-exposure or post-exposure prophylaxis in community settings. Lancet Global Health, 11: e1494-e1495, 2023. Published online 19 September 2023. Full image credit: Fighting NTDs in Cross River State, Nigeria. Image by RTI International/Ruth McDowall. Available at www.flickr.com/photos/rtifightsntds/35590031472 under a Creative Commons licence CC BY-NC-ND 2.0.