Page 70 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 5 of 7 Opinion Paper

those for whom oral tenofovir-based PrEP is not an exposure prophylaxis (PEP). Most data supporting the use of
appropriate option, either on account of contraindications to PEP are derived from animal transmission models, prevention
the drug itself, or on account of other factors related to oral of mother-to-child transmission trials, observational studies
formulation or the requirement to take pills regularly. For of healthcare workers receiving PEP following occupational
such individuals, alternative PrEP options are essential. HIV exposure, and observational cohorts and case studies of
PEP following potential sexual exposure.
Early studies of long-acting rilpivirine (alone or in combination
with a long-acting integrase inhibitor, cabotegravir) confirmed Adherence to the full 28-day course of PEP has been shown
the initial safety, acceptability and pharmacokinetic to be poor, with only 56.6% (95% CI 50.9–62.2%; t 0.25) of
2
characteristics of the formulation. 53,54 Plasma, rectal and those eligible completing the course, and lower in
60
cervical fluid sampling and limited rectal and vaginal biopsies adolescents than in adults. A significant proportion of PEP
after single doses of 300 mg – 1200 mg long-acting rilpivirine discontinuation is related to adverse events, indicating that
in one of these studies demonstrated prolonged rilpivirine better tolerated PEP regimens are needed. A systematic
exposure in plasma as well as the genital tract for 84 days. In review of observational data concluded that tenofovir-based
this study, one female participant subsequently experienced PEP regimens were better tolerated than those using
incident HIV-1 (wild-type virus) infection after a single episode zidovudine, while the optimal third drug to use was a little
of unprotected vaginal intercourse approximately 41 days less clear. While raltegravir was well tolerated, other factors
after she received the 300 mg rilpivirine injection. Viraemia such as twice daily dosing, availability and cost were
peaked on day 115, and at this point, a mixed population of identified as limitations to the use of raltegravir as the third
101 K/E was detected and ART was initiated. Resistance was drug, particularly in resource-limited settings. 61
selected by high levels of viral replication in the face of low
rilpivirine concentrations. The viral population reverted to Subsequently, a number of PEP observational studies using
predominantly wild-type by day 199. This incident infection newer antiretrovirals have been undertaken. One single-arm
illustrates the risk of subtherapeutic concentrations of long- study and one observational cohort used rilpivirine for PEP.
acting agents that are not high enough to prevent infection but The single arm study used a STR of rilpivirine combined
are sufficient to select for resistance. 56
with TDF and FTC for 28 days in 100 HIV-uninfected
men who have sex with men. Post-exposure prophylaxis
A subsequent phase 1 study enrolled 36 HIV-negative completion rates were high at 92% and adherence rates
participants and alternately assigned them to receive one
intramuscular dose of long-acting rilpivirine, either 1200 mg at 98.6% (standard deviation [s.d.], 2.4) by pill count.
62
or 600 mg. The safety and acceptability findings were in line Discontinuations for adverse events were low (1%). These
with previous studies. These findings were confirmed in a results are similar to the findings of a French observational
multiple dose phase of this study. 57 cohort study including 129 participants, which evaluated the
safety, tolerability, adherence and efficacy of a 28-day course
HPTN 076 is a double-blind, randomised study, which of single-tablet RPV/TDF/FTC commenced within 48 hours
compared the safety of long-acting rilpivirine1200 mg every 8 of potential exposure to HIV. 63
weeks to placebo, following a 4-week run-in oral phase, for
PrEP in low-risk, sexually active HIV-uninfected women. The In these studies, adverse events were commonly reported by
study demonstrated no significant differences between the participants but were of low grade, and there were no
two arms with respect to adverse events. It also showed that seroconversions. With the high number of participants
for 92% of participants, plasma rilpivirine concentrations were completing their PEP regimens in these studies, rilpivirine is
above the protein-adjusted IC . Currently, HPTN 076 study an attractive option as a third drug for PEP regimens, offering
90
has only reported safety, acceptability and pharmacokinetic the advantages of cost and coformulation (although the
findings, 58,59 and the long-acting rilpivirine will not be taken coformulation is not available in many countries). With more
forward into PrEP efficacy studies at this stage. lower- and middle-income countries introducing dolutegravir
into first-line ART, another potential advantage of rilpivirine-
To date, no studies using rilpivirine oral formulations as PrEP based PEP is the lack of overlapping resistance profiles
have been conducted, except where it has been used as an between rilpivirine and dolutegravir.
initial run-in phase to establish tolerability prior to progressing
onto the administration of injectable formulations. Ethical consideration

The role of rilpivirine in HIV This article followed all ethical standards for a research
without direct contact with human or animal subjects.
prevention: Post-exposure
prophylaxis Conclusion

While a number of PrEP randomised controlled trials have Many lower- and middle income countries use efavirenz-
been conducted with various drug regimens, there are no based regimens for first-line ART. Efavirenz has good efficacy
randomised studies on antiretroviral regimens for post- and relatively good tolerability, is available in fixed-dose

http://www.sajhivmed.org.za 63 Open Access