RESUMO
BACKGROUND: Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa. METHODS: CARES is a randomised, open-label, non-inferiority trial being conducted at eight sites in Uganda, Kenya, and South Africa. Participants with HIV viral load below 50 copies per mL on oral antiretroviral therapy and no history of virological failure were randomly assigned (1:1; web-based, permuted blocks) to receive cabotegravir (600 mg) and rilpivirine (900 mg) by intramuscular injection every 8 weeks, or to continue oral therapy. Viral load was monitored every 24 weeks. The primary outcome was week 48 viral load below 50 copies per mL, assessed with the Food and Drug Administration snapshot algorithm (non-inferiority margin 10 percentage points) in the intention-to-treat exposed population. This trial is registered with the Pan African Clinical Trials Registry (202104874490818) and is ongoing up to 96 weeks. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 512 participants (295 [58%] female; 380 [74%] previous non-nucleoside reverse transcriptase inhibitor exposure). Week 48 viral load was below 50 copies per mL in 246 (96%) of 255 participants in the long-acting therapy group and 250 (97%) of 257 in the oral therapy group (difference -0·8 percentage points; 95% CI -3·7 to 2·3), demonstrating non-inferiority (confirmed in per-protocol analysis). Two participants had virological failure in the long-acting therapy group, both with drug resistance; none had virological failure in the oral therapy group. Adverse events of grade 3 or greater severity occurred in 24 (9%) participants on long-acting therapy and ten (4%) on oral therapy; one participant discontinued long-acting therapy (for injection-site reaction). INTERPRETATION: Long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programmes. FUNDING: Janssen.
RESUMO
There are limited data on the prevalence of risky sexual behaviours in individuals failing first-line antiretroviral therapy (ART) and changes in sexual behaviour after switch to second-line ART. We undertook a sexual behaviour sub-study of Ugandan adults enrolled in the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial. A standardized questionnaire was used to collect sexual behaviour data and, in particular, risky sexual behaviours (defined as additional sexual partners to main sexual partner, inconsistent use of condoms, non-disclosure to sexual partners, and exchange of money for sex). Of the 79 participants enrolled in the sub-study, 62% were female, median age (IQR) was 37 (32-42) years, median CD4 cell count (IQR) was 79 (50-153) cells/µl, and median HIV viral load log was 4.9 copies/ml (IQR: 4.5-5.3) at enrolment. The majority were in long-term stable relationships; 69.6% had a main sexual partner and 87.3% of these had been sexually active in the preceding six months. At enrolment, around 20% reported other sexual partners, but this was higher among men than women (36% versus 6.7 %, p < 0.001). In 50% there was inconsistent condom use with their main sexual partner and a similar proportion with other sexual partners, both at baseline and follow-up. Forty-three per cent of participants had not disclosed their HIV status to their main sexual partner (73% with other sexual partners) at enrolment, which was similar in men and women. Overall, there was no significant change in these sexual behaviours over the 96 weeks following switch to second-line ART, but rate of non-disclosure of HIV status declined significantly (43.6% versus 19.6%, p <0.05). Among persons failing first-line ART, risky sexual behaviours were prevalent, which has implications for potential onward transmission of drug-resistant virus. There is need to intensify sexual risk reduction counselling and promotion of partner testing and disclosure, especially at diagnosis of treatment failure and following switch to second- or third-line ART.