Page 266 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 2 of 10 Original Research

recommended for use in non-pregnant women who are AIDS Clinical Society guidelines, there are sufficient data
trying to conceive or during the first trimester of pregnancy from use in pregnancy to recommend RPV as an alternative
because of concerns about a possible increased risk of neural agent in ART-naive pregnant women with viral loads
tube defects, a viable alternative to DTG is needed. There is, ≤ 100 000 copies/mL and CD4+ counts > 200 cells/mm .
3 3,33
9
thus, an unmet need for additional efficacious, well-tolerated
and more affordable alternative ART regimens, particularly This study was, therefore, designed to examine the utility of
in LMICs. 10 switching to the STR of TDF/FTC/RPV in LMIC patients
with suppressed viral loads, who were on an NNRTI-based
Rilpivirine (RPV; TMC278) is a second-generation non- first-line ART.
nucleoside reverse transcriptase inhibitor (NNRTI) with a
good safety profile and convenient once-daily dosing, with Methods
11
a reduced special effort access price of US$40 per patient per
year in sub-Saharan Africa and least developed countries, Switching at Low HIV-1 RNA into Fixed Dose Combinations
12
making it a good candidate component for an affordable (SALIF) was a 48-week, multicentre, phase 3b, randomised,
STR in LMICs. 13,14,15,16,17 RPV, in combination, is indicated in open-label study designed to demonstrate non-inferiority of
treatment-naïve patients 12 years of age and older with a RPV to EFV (both coformulated with TDF and FTC) in
viral load of HIV-1 RNA ≤ 100,000 copies/mL. Tenofovir maintaining HIV-1 RNA suppression (defined as HIV-1 RNA
18
disoproxil fumarate (TDF)/lamivudine (3TC) or emtricitabine < 400 copies/mL) among adult patients in LMICs on first-
(FTC) with RPV is listed as a ‘preferred’ first-line regimen in line NNRTI-based ART (with EFV or NVP) with HIV-1 RNA
3
European guidelines, has recently been adopted as a < 50 copies/mL. The study was conducted at 23 sites in
19
preferred first-line regimen in South African guidelines and Cameroon, Kenya, Senegal, South Africa, Uganda and
is a recommended ‘alternative’ regimen in the United States Thailand from 23 August 2013 to 27 October 2015.
and Thailand. 2,20
Ethics committee approval was obtained at all participating
Approval of RPV was based on findings from two double- centres in accordance with the principles of the 2008
blind, placebo-controlled, phase 3 trials, ECHO and THRIVE, Declaration of Helsinki. Central randomisation was based on
comparing RPV with EFV, most commonly in combination a computer-generated schedule prepared before the study by
with TDF and FTC, in treatment-naive patients. 6,7,21 In a 48- the sponsor. Randomisation was balanced by using randomly
week pooled analysis of these trials, RPV was non-inferior to permuted blocks and stratified by baseline NNRTI. A pre-
EFV both in patients with viral loads ≤ 100 000 copies/mL specified interim analysis was performed once all patients
(90% vs. 84%; 95% confidence interval [CI]: +1.6, +11.5) and
with viral loads > 100 000 to ≤ 500 000 copies/mL (80% vs. had reached week 24 or discontinued earlier, and was
83%; 95% CI: –9.8, +3.7), but non-inferiority was not reviewed by an independent data monitoring committee.
21
34,35
achieved for patients with viral loads > 500 000 copies/mL Data from this study have been presented previously.
(70% vs. 76%; 95% CI: –20.4, +8.30). In addition to these
pivotal trials using the individual agents, the STR of TDF/ All patients remained on study until the last patient reached
FTC/RPV has been evaluated in both treatment-naive the week 48 visit. Patients were then switched to an
patients and virologically suppressed patients, including in investigator-selected treatment according to local prescribing
at least one LMIC setting. In these studies, TDF/FTC/RPV practice. In countries where a RPV-based regimen was not
was found to be non-inferior to several different ART yet available, patients with suppressed HIV-1 RNA levels
regimens, including protease inhibitor (PI)- and NNRTI- receiving TDF/FTC/RPV could continue in post-trial access
based combinations. 22,23,24,25 Hence, in Europe and the United programmes until RPV was publicly available in the country.
States, TDF/FTC/RPV is indicated for use in treatment-naive
patients with HIV-1 RNA ≤ 100 000 copies/mL and for Study patients
patients with suppressed viral load for ≥ 6 months prior to
switching therapy and without known resistance-associated The study included adults (≥ 18 or 21 years of age, depending
mutations to NNRTIs, TDF or FTC. 26,27 on national legislation of patient’s country) with documented
HIV-1 infection, who had been receiving first-line NNRTI-
Preclinical studies of RPV showed no evidence of teratogenicity based ART (defined as two nucleoside reverse transcriptase
RPV and therefore may be an option in populations with inhibitors [NRTIs] with either EFV or NVP) for at least 1 year,
large proportions of HIV-infected women of childbearing and the same ART for at least 8 weeks, before screening.
potential who have access to regular viral load monitoring. Previous changes in NRTI background regimen were
28
Pharmacokinetic studies of RPV in pregnancy reveal that allowed, but patients who had previously switched from
most women achieve effective plasma concentrations of EFV to NVP for toxicity reasons were not eligible. At
RPV. 29,30,31 The Antiretroviral Pregnancy Registry showed no screening, eligible patients had to have suppressed viral
increased risk in birth defects after first trimester RPV loads, commonly accepted to be a plasma HIV-1 RNA < 50
36
3
exposures as of January 2018. Furthermore, according to copies/mL, a CD4+ cell count of more than 200 cells/mm ,
32
both the US Department of Health and Human Services and a preference to change their current ART for reasons of
Recommendations for Use of Antiretroviral Drugs in simplification and/or NRTI toxicity. Patients also needed to
Pregnant HIV-1-Infected Women and the 2017 European have access to at least one meal a day and have a normal
http://www.sajhivmed.org.za 259 Open Access