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If a PrEP user’s risk changes, that is, declines, or one wishes Prevenir studies 26,41 that on-demand (i.e. sex or coital based
to stop PrEP for any reason, it should be affirmed that PrEP is dosing of PrEP) is effective for MSM and TG women and can
not a lifelong intervention and that it is fine to stop. It is be used as an alternative to daily dosing.
advised to take PrEP for up to 28 days after the last potential
exposure to HIV (although this is not based on clinical On-demand PrEP involves the so-called ‘2:1:1 strategy’.
evidence and alternative HIV prevention advice and PrEP users are advised to take two pills of TDF-based PrEP
commodities should be discussed). Clients should be invited (i.e. a double dose) 2–24 h before sex. If sex occurs, they
to return to discuss PrEP at any point in future. should follow up with one pill per day for the following
2 days after sex.
Risk disinhibition: Pre-exposure prophylaxis is highly
efficacious and therefore it is unlikely even with more This strategy allows minimisation of unnecessary PrEP
condomless sex that HIV infection will occur. Most studies doses when HIV exposure is unlikely (no sex) and therefore
have shown that increased access to care has resulted in less might decrease the risk of cumulative side effects. The
risky sex but in practice PrEP may result in more STIs and strategy might suit individuals who do not want to take
unintended pregnancies. For effective PrEP services, STI pills daily, allowing prevention doses to be focused around
screening, appropriate treatment and prevention as well as the time of HIV exposure risk. Should someone initiate on-
contraception should be offered as part of an integrated demand PrEP, they should be counselled on the strategy
sexual and reproductive health service at each PrEP clinical and similar initiation precautions and investigations
consultation. should be done. Human immunodeficiency virus status
should be confirmed as negative, they should be considered
for renal function testing and should attend their health
Sexually transmitted infections and pre-exposure provider regularly for STI screening and repeat HIV testing.
prophylaxis: Where feasible, a sexual history and a targeted New prescriptions should be administered as often as
examination is recommended to guide further screening and required.
management, taking into account that STIs occur at all
anatomic sites including oral, vaginal, penile and anal sites.
The frequency of screening should be individualised and Newer pre-exposure prophylaxis options
guided by the sexual history. We recommend that STI A recently added ARV shown to be effective for oral PrEP is
screening should occur at least annually and more frequently a tenofovir (TFV) pro-drug called TAF that is approved in
(6 monthly) in key populations such as MSM, 36,37 pregnant combination with other ARV agents for the treatment of
women 38,39,40 and sex workers. High rates of asymptomatic HIV-1 infection in adults and paediatric patients. Tenofovir
Chlamydia trachomatis (CT) are occurring amongst young alafenamide has PK properties that distinguish it from TDF,
women and MSM in the region. For this reason, where resulting in clinically meaningful benefits that improve
possible, nucleic acid amplification test (NAAT) testing for safety and increase the efficacy of TAF over TDF in PrEP.
gonorrhoea and CT are highly recommended, but these tests The lower levels of circulating TFV have consistently been
are expensive and not always available. Syndromic STI associated with improved measures of renal and bone safety
screening and management should be offered as an laboratory markers. Emtricitabine + TAF fixed dose
alternative. combination pill (F/TAF) was shown in the recently
published Emtricitabine and tenofovir alafenamide vs
emtricitabine and tenofovir disoproxil fumarate for HIV
Post-exposure prophylaxis to pre-exposure prophylaxis: pre-exposure prophylaxis (DISCOVER) trial to be non-
Individuals who frequently require post-exposure inferior to F/TDF and has thus been licensed by the FDA for
prophylaxis (PEP) for HIV exposure may benefit from PrEP. oral PrEP use in men and TG women. An equivalent trial
42
On completion of 28 days of triple ARV PEP therapy, oral is being designed for cisgender women in which TAF use in
PrEP may be continued with ongoing maintenance as before. pregnancy will also be explored.
Individuals who have a break between PEP and PrEP
initiation should initiate as recommended above. Long-acting cabotegravir which is a depot injectable
integrase PrEP agent has just been shown to be non-inferior
Broaden pre-exposure prophylaxis modalities to to oral TDF/FTC in a randomised clinical trial of MSM and
43
include on-demand pre-exposure prophylaxis in TG women (HPTN 083). The companion study of
men who have sex with men and transgender cabotegravir long acting in African women is still underway
women (HPTN 084, the Life Study, NCT03164564). i
On demand pre-exposure prophylaxis i.With regard to long-acting single-agent injectable antiretroviral cabotegravir in the
pre-exposure prevention (PrEP) of HIV infection/transmission to HIV-uninfected
There is now robust evidence from the Intervention Préventive women (Study HPTN 084) and men (Study HPTN 083), both demonstrate superior
efficacy versus standard oral PrEP. In the HPTN 084 Study, cabotegravir given every
de l’Exposition aux Risques avec et pour les Gays (IPERGAY), two months was 89% more effective than daily pills at preventing HIV acquisition.
London, 9 November 2020. https://clinicaltrials.gov/ct2/show/NCT03164564. (HTPN
and Intervention Préventive de l’Exposition aux Risques avec 084); https://clinicaltrials.gov/ct2/show/NCT02720094. (HTPN 083). Editor’s
et pour les Gays (IPERGAY) Open Label Extension (OLE) and comment: Note that this data will still require approval from international and local
agencies. Cabotegravir is not currently registered for use in South Africa.

http://www.sajhivmed.org.za 70 Open Access