Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Cabotegravir demonstrated a statistically significant reduction in HIV acquisition compared to TDF-FTC in the HPTN 083 and HPTN 084 trials, with hazard ratios of 0.34 and 0.12 respectively. This indicates a clear clinical advantage over the standard of care, supported by Phase 3 evidence.
Cost effectiveness
The cost-effectiveness estimates for cabotegravir were within the acceptable range for NHS resources when compared with no PrEP, with an ICER around £20,000 to £30,000 per QALY gained, indicating marginal cost-effectiveness.
Quality of life
No direct HRQoL data was collected in the pivotal trials. The committee assumed a disutility of -0.11 associated with living with HIV, but there were no specific improvements in HRQoL reported for cabotegravir compared to standard care.
Supporting Domains
Safety and Adverse Effects
Cabotegravir was reported to have a very good safety profile with mostly mild or moderate adverse events, and the committee noted that serious adverse events were rare, indicating a favorable tolerability compared to existing therapies.
Comparator Selection
The trials compared cabotegravir against TDF-FTC, which is the standard of care for oral PrEP, and also considered no PrEP as a comparator for those unable to take oral PrEP, making the comparator selection appropriate.
Patient Population and Subgroups
The patient population included high-risk adults and adolescents, and the committee recognized the unmet need for those who cannot take oral PrEP, indicating broad generalizability with minor gaps.
Care Pathway Integration
Cabotegravir can be integrated into existing healthcare pathways with minor adjustments, as it is expected to be administered in level 3 sexual health services, which are already equipped for such treatments.
Resource Use and Cost Implications
The implementation of cabotegravir may lead to a high resource burden due to the need for administration and monitoring, raising concerns about its budget impact, although it is manageable.
Evidence Quality and Robustness
The evidence base is supported by multiple Phase 3 RCTs with low bias, although there are some uncertainties regarding generalizability due to trial locations not being in the UK.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the baseline risk of HIV acquisition and the engagement of underserved populations with healthcare services, which could impact the overall effectiveness of cabotegravir.
