IAS 2025: Switching to injectable CAB/RPV-LA with detectable viral load: results from the OPERA cohort

28 July 2025. Related: Conference reports, Antiretrovirals, Treatment strategies, IAS 13th Kigali 2025.

Simon Collins, HIV i-Base

IAS 2025 included results from two studies from the large US OPERA cohort in people who started injectable CAB/RPV-LA when their viral load was still detectable. [1, 2]

It also included results from the ANRS IMPALA study which looked at the same approach in a randomised study in Uganda, Kenya and South Africa. [3]

These results are important because even though CAB/RPV-LA is only approved as a switch option in people with viral load <50 copies/mL on oral ART, it is perhaps most likely to benefit people whose viral load is still detectable due to adherence difficulties with oral treatment.

Results in 368 people were presented by Ricky Hsu from AIDS Healthcare Foundation, New York in an oral presentation.

The OPERA cohort includes medical records of almost 152,000 adults living with HIV attending more than 100 clinics across the US. Of these, 3304 (less than 3%) started CAB/RPV-LA between January 2021 and December 2023 and were not enrolled in a clinical study – and 368/3304 (11%) started injectable ART with viral load >50 copies/mL on oral therapy.

Baseline characteristics, only provided for these 368 participants, included 27% older than 50 years, 30% women, 57% African-American, 18% Hispanic, 49% gay and bisexual men and 63% were living in the US South.

Clinical characteristics included 29% with BMI >30, 80% had a comorbidity and one-third had a history that included an AIDS-defining infection. There was a median 9 years since HIV diagnosis (IQR: 3 to 17) with time on current oral ART of 17 months (IQR: 8 to 37 months). This was INSTI-based in 68%, PI-based in 9%, NNRTI-based in 8% and >1 of these core drugs was used by 12%. These details are important because of the potential of resistance at baseline to injectable ART. Although detectable, the median viral load was still low: 120 copies/mL (IQR: 61 to 2535) and the median CD4 count was roughly 575 cells/mm³ (IQR: 350 to 800).

Adherence results were based on a window of one week either side of the planned injection time, but were complicated by the presentation combining monthly and twice-monthly schedules. Roughly 80% of people started on a two-monthly injection schedule which increased to 93% by the end of follow-up.

Adherence was reported at 90% for the first two injections, with 37/368 people taking longer than 67 days before the second injection. Only 59% of subsequent injections were categorised as being on time, with 33% being either at 38-52 days (monthly) or 68-112 days (two-monthly), and 38/368 participants missed an injection completely.

Overall, only 258 of the total 368 participants (70%) remained on injectable ART for a median of 12 cumulative months (IQR: 8 to 19 months).

Virological results were also complicated by missing data. Only 306/368 had a viral load test result within six months and of these, 259/306 had at least one viral load result <50 copies/mL and 30/313 (12%) with any viral load result never suppressed to <50 copies/mL.

Only three participants were reported to have confirmed viral failure defined, although this was only among those with viral load results available. Viral failure was defined as two consecutive results >200 copies/mL. These three cases were presented in detail. All 3/3 achieved undetectable viral load at some point. Of these, 2/3 rebounded with two-class resistance and the third resuppressed on monthly CAB/RPV-LA using an unusual high-dose (600/900 mg) with fostemsavir.

The study concluded that 259 participants achieved undetectable viral load within 6 months of starting CAB/RPV-LA.

This was 70% by ITT analysis rather than the 85% reported based on available data, and understanding the outcomes for the remaining 30% is more difficult.

A second analysis from the OPERA cohort included a subset of 105 women from the above study presented as a poster. [2]

In this group, the median viral load when switching to injectable ART was 1090 copies/mL (IQR: 89 to 24,700). Of these, 69/105 (65%) were on CAB/RPV-LA at the time of the analysis after a median follow-up of 19 months (IQR: 13 to 25). Roughly 39% received all injections on time, 33% had at least one delayed injection and 17% missed at least one injection. Of note, only 66 women had at least one viral load test available for the analysis and this included several cases of viral failure after a median of 13 months (IQR: 9 to 17).

Comment

The results are encouraging for people who switch with a relatively low viral load and who are able to adhere to the schedule of injections.

However, the lack of viral load data for many of the participants is a significant limitation of both studies, especially as viral load should be routinely checked at every visit. Collecting this real-world data is also complicated by this being a vulnerable population, who for other complex reasons may not have a stable connection to HIV care.

This makes it important to clearly define the denominator in each analysis and to compare long-term outcomes from long-acting injections compared to similar people who continue on failing oral ART. 

Although a growing number of people achieved and maintained undetectable viral load, many of whom are likely to have had a complex HIV history, these are still very small numbers – similar to other studies reporting outcomes from people with detectable viral load when switching to CAB/RPV-LA. [4, 5, 6]

It is therefore good that ViiV is currently recruiting for the randomised phase 3b CROWN study in Spain and the US. This open-label study will enrol adolescents and adults with viral load >1000 to <100,000 copies/mL and documented adherence difficulties with oral ART. [7]

CID also published results of another US cohort switching to all injectable ART in people struggling with adherence to oral ART. [8]

References

1. Hsu R et al. Real-world effectiveness of CAB+RPV LA in individuals with HIV viremia at therapy initiation. IAS 2025. 13-17 July 2025. Oral abstract.
   https://conference.ias2025.org/media-1144-art-strategies (webinar, login required)
2. Altamirano J et al. Clinical outcomes among women in the OPERA cohort initiating CAB+RPV LA with viral loads ≥ 50 copies/mL. IAS 2025), 13-17 July, Kigali. Poster abstract WEPEB036.
   https://programme.ias2025.org/Abstract/Abstract/?abstractid=2079
3. IAS 2025: Long-acting CAB/RPV in people with suboptimal adherence: IMPALA study results at 48 weeks. HTB July 2025.
   https://i-base.info/htb/51876
4. Spinelli MA et al. HIV Viral Suppression With Use of Long-Acting Antiretroviral Therapy in People With and Without Initial Viremia. JAMA. 2025;333(16):1451–1453. doi:10.1001/jama.2025.0109
   https://pubmed.ncbi.nlm.nih.gov/40048173
5. Sension MG et al. Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. Infect Dis Ther. 2023;12:2807-2817.
   https://pubmed.ncbi.nlm.nih.gov/37966701
6. Hickey MD et al. Suppression Rates at 48 Weeks in People With HIV Starting Long-Acting Cabotegravir/Rilpivirine With Initial Viremia. Clin Infect Dis. 2025 Apr 30;80(4):864-870. doi: 10.1093/cid/ciae500.
   https://pubmed.ncbi.nlm.nih.gov/39367871
7. Clinicaltrials.gov. A Study to Evaluate the Effectiveness of Long-acting (LA) Cabotegravir CAB) + Rilpivirine (RPV) LA When Given to Participants With Detectable HIV-1
   https://clinicaltrials.gov/study/NCT06694805
8. Switching to long-acting injectable ART with detectable viral load in people struggling with oral ART. HTB 8 August 2025).
   https://i-base.info/htb/52279