By Mercy Kachenge
Injectable treatment with cabotegravir and rilpivirine proved just as effective in maintaining viral suppression as standard oral antiretroviral treatment in a large trial in Africa, despite less intensive viral load monitoring than previous studies.
According to a study titled ‘Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial’ reveals that long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programs.
“This trial provides crucial evidence for the efficacy, safety, acceptability and potential feasibility of switching from standard oral therapy to long-acting therapy in the public health approach, the essential first step for considering possible use of long-acting therapy in treatment programs,” The study reads in part.
According to the study the trails aim to evaluate the effectiveness of switching to long-acting therapy (Cabotegravir & Rilpivirine injections every 8 weeks) compared to maintaining daily oral therapy in adults with established virological suppression in Sub Saharan Africa, Conducted at Uganda, Kenya and South Africa.
The study is the first test of injectable treatment in people with HIV in Africa. The first injectable regimen, consisting of the integrase inhibitor cabotegravir and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, is already approved for use in Europe and North America. Treatment is given by intramuscular injection at a health facility every two months.
The trial which is registered with Pan African Clinical Trials recruited adult participants who have been on a specific antiretroviral regimen with stable load suppression.
Participants were randomly assigned in ratio of 1:1 to either long-acting therapy or oral therapy that entails using a web based on the third drug class at screening.
The trial management team was blinded to unmasked data except for serious adverse events and pregnancy reports.
At first 4 weeks post, participants in the long-acting group either take oral Cabotegravir `rilpivirine or continue their current regimen to assess tolerability.
Participants received injections of cabotegravir ` rilpivirine at 4, 16, 24, 32,40,48 weeks. The participants who missed an injection were given oral options since World Health Organization (WHO) recommended for oral therapy participants was used.
Primary study outcome was to achieve a viral load below 50 copies per ML at week 48 using a modified FDA snapshot algorithm that allowed for temporary regimen changes within 31 days.
Secondary outcomes entailed confirmed virological failure (two consecutive values at least 200 copies per ML by week 48 and other measure of viral suppressions or failure. Additional post hoc analyses looked at incident of obesity and hypertension by week 48.
Laboratory parameters` incidence of grade 3 or higher events, HIV disease progression, injection site ` treatment discontinuation events.
Primary outcome was analyzed in the intention to treat exposed population (all those who received a dose assigned intervention).
The between group difference was estimated using the Cochran- Manteln-Haenszel weighted Miettinen `Nurminen method adjusting for the drug class screening.
Non inferiority of long-acting therapy was determined if the lower limit of the two-sided 95percent confidence interval for the difference between groups in viral suppression was at least -10percent.
A total of 1039 participants were screened ` 512 were randomly assigned to the long-acting therapy ` 257 to the oral therapy. All participants took at least one dose of the randomly assigned study medication were included in the intention to treat exposed population. Four (1percent) of 512 withdrew from follow up before week 48.
Baseline characteristics were similar between randomized groups and broadly representative of people receiving HIV treatment in Sub Saharan Africa of the 512 participants,295 (58percent) were female ,108 (21percent) had obesity ` 380 (74percent) had previous (non-nucleoside reverse transcriptase inhibitors (NNRTI) exposure. Of these with sequence available from DNA in peripheral blood monocular stored cells at baseline 223 (54percent of the 414 had subtype A1 virus 51(14percent 0 of 377 had archived rilpivirine resistance mutations 1and 29 (16percent) of 180 had archived cabotegravir resistance mutations.
“The study found out that switching to long-acting therapy with cabotegravir and rilpivirine injections every 8 weeks was non inferior to continuing daily oral therapy. Virological suppression was maintained in over 96percent exceeding the 95percent WHO target considered necessary to reduce HIV population incidence.”
The main advantage of long-acting therapy for people living with HIV appears to be increased treatment satisfaction, observed in this and all previous trials. This is driven by increased convenience by reduced fear of disclosure which is also a major consideration in Sub Saharan Africa.
The limitation of this trial is use of open label treatment but masking would have required both placebo injections and pills, decreasing feasibility and preventing meaningful assessment of participants perception; the high retention rate and laboratory based primary outcome reduce like hood of substantial bias in assessment of efficacy outcomes.
The study confirmed the previous trials done mainly in North America and Europe, enrolling people with viral suppression on various oral regimens which shown that switching to a two-drug regimen of cabotegravir (an INSTI) and rilpivirine (an NNRTI) given by intramuscular injection once every 4 weeks or 8 weeks, maintains viral suppression and increases treatment satisfaction.
“This is one of the recommended individualized treatment options for virologically suppressed people in treatment guidelines for these settings, with the exception of those with hepatitis B virus (HBV) infection who need to maintain NRTIs in their regimen for activity against both infections,” the study reveals.
HIV treatment guidelines recommend an HIV viral load test to be done within 4–8 weeks after switching to long-acting therapy, and 8-weekly thereafter.
