Page 272 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 8 of 10 Original Research

Discussion compared with EFV seen in treatment-naive patients.
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However, the subgroup analysis of patients who switched
SALIF examined the effect of switching to TDF/FTC/RPV from NVP to either RPV or EFV showed tolerability
in patients from LMICs with suppressed viral loads who differences in favour of RPV.
were on an NNRTI-based first-line ART. This study is
important because it provides additional data on the utility The strength of this study is that it illustrates the benefit of
of TDF/FTC/RPV as a viable alternative for virologically STRs for patients in resource-limited settings who have
suppressed patients on first-line NNRTI-based regimen in tolerability issues with currently available NNRTIs and who
LMICs and in a study population that is predominantly are already virologically suppressed. The main limitation of
female because women comprised > 60% of the patients the study was that all patients entering the TDF/FTC/RPV
enrolled. arm changed the previous NNRTI component of their
regimen, while > 50% of the patients in the TDF/FTC/EFV
The SALIF data add to the evidence from the SPIRIT study, arm had previously received an EFV-based regimen.
which examined TDF/FTC/RPV STR as a switch option Switching to a new regimen may confer a potential risk for
from a PI-based regimen in mostly Caucasian men in high- new tolerability or safety issues. Furthermore, the treatment-
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income settings, and the NEAR-RWANDA study, which emergent neuropsychiatric events in the subgroup of
demonstrated non-inferior efficacy and comparable safety of patients switching from EFV are discordant with general
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a TDF/FTC/RPV STR versus NVP-based ART in Rwanda. tolerability data (that show that EFV is associated with
Taken together, these data support the use of RPV-based STR higher rates of neuropsychiatric events compared with
regimens in virologically suppressed patients. Given that other NNRTIs, including NVP). This suggests that our
48
viral load measurements prior to ART initiation are not safety findings are subject to some inherent bias of the study
routinely conducted in many LMICs, RPV-based STR design. This negative bias might explain why the ITT
regimens are an appropriate switch option for patients with analysis showed no differences in tolerability, while other
suppressed viral loads. These patients have demonstrated studies in treatment-naive patients have demonstrated a
sufficient adherence and might benefit from a switch, generally more favourable tolerability profile of RPV
particularly given concerns around the safety profile of EFV- compared with EFV. 6,7,21,22,24,47 A control group of non-
and NVP-based regimens.
switchers (or deferred switchers) staying on their original
ART might help address such inherent biases in future
Recent reports from Europe have provided encouraging switch studies. Another limitation of the study is the open-
data on the tolerability of TDF/FTC/RPV in clinical label design, which may influence the reporting of side
practice, which may be transferable to the LMIC effects and discontinuation rates. For instance, QT
settings. 38,39,40,41,42 In addition, the introduction of STRs prolongations were reported in three patients on TDF/
containing tenofovir alafenamide (TAF) 25 mg instead of FTC/RPV and three patients receiving TDF/FTC/EFV;
TDF 300 mg, or an STR of DTG/RPV, could potentially offer while two of the three patients receiving TDF/FTC/RPV
increased long-term tolerability at lower dosing and, discontinued their regimen, none in the EFV arm
eventually, lower costs. 43,44,45 For virologically suppressed discontinued. A caveat to the generalisability of the study
patients such as those in the SALIF trial, who are stable on results is that trial candidates with CD4 cell counts < 200
ART and have already demonstrated high adherence, the cells/mm were excluded. Also, it should be noted that the
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risk of virologic failure is considered low. Therefore, definition of viral suppression used in the study was < 400
switching to an STR may further motivate patients to stay copies/mL rather than < 50 copies/mL; this was chosen to
on therapy while leading to fewer medication errors and reflect real-life practice in LMICs and to account for blips,
supporting long-term adherence. This is in line with current and is within the recommended WHO guidance to use a
normative guidance for mature ART programmes, which definition < 1000 copies/mL in LMICs. Finally, our study
recommends differentiated models of care for patients who required participants, as an inclusion criterion, to have
are stable on ART. access to at least one meal a day, a situation that does not
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necessarily always pertain in sub-Saharan Africa and other
Increased rates of rash and neuropsychiatric events have LMIC regions.
been reported following RPV and EFV treatment; 21,47
therefore, patients in SALIF were closely monitored for these Conclusion
AEs. In studies in treatment-naive patients, most rash events
(3% with RPV vs. 14% with EFV) occurred during the first In adults from LMICs with suppressed viral load on first-line
48 weeks of treatment, with few additional patients NNRTI-based therapy, switching to an STR of TDF/FTC/
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experiencing rashes during the second year. SALIF included RPV was non-inferior to an STR of TDF/FTC/EFV in
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patients who had already been successfully treated with maintaining high rates of viral suppression, with comparable
NNRTIs, and rashes were rarely seen. EFV can cause safety at 48 weeks. Our findings support the use of TDF/
neuropsychiatric side effects, which often resolve within the FTC/RPV as a viable alternative to both EFV- and NVP-
first weeks of treatment. This study could not confirm based regimens in LMICs, where access to a wider variety of
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the improved central nervous system tolerability of RPV affordable ART options is urgently needed.

http://www.sajhivmed.org.za 265 Open Access