HIV During Dapivirine Vaginal Ring Use Unlikely to Affect Long-Term Management

Seroconversion to positive HIV status during dapivirine vaginal ring use does not increase the risk for poor outcomes of subsequent antiretroviral therapy in women.

Seroconversion to HIV positivity during dapivirine vaginal ring use does not increase the risk for poor outcomes of subsequent antiretroviral therapy (ART) in women, according to results of a post hoc analysis published in Clinical Infectious Diseases.

Data for this analysis were sourced from The Ring Study and the DREAM open-label extension trial. Women who experienced HIV seroconversion during the 2 trials were offered to enroll into the IPM 007 study conducted between 2012 and 2019 in South Africa, which was an observational study of women who were referred to local treatment clinics for HIV management and ART. The primary outcomes for this analysis were clinical presentation and outcomes of subsequent ART among women who had been previously randomly assigned in a 2:1 fashion to receive either the dapivirine vaginal ring or placebo.

Among the 330 patients who developed HIV infection during the parent studies, 53.0% of placebo recipients and 31.8% of DVR recipients seroconverted during The Ring Study and 15.2% of DVR recipients seroconverted during the DREAM study.

Of the 151 patients included in this analysis, all were Black, the mean age was 26.6 years, and 17.9% were receiving ART at the time of enrollment. The time from HIV seroconversion to enrollment in this analysis (range, 128.9-140 days) did not significantly differ between patients assigned to the ring vs placebo groups in either of the previous parent studies.

These results demonstrate that becoming HIV infected while using the DVR is unlikely to have any deleterious effect on management of HIV infection in the longer term.

Analysis among patients receiving ART (n=132) at the 12-month follow-up visit showed 43.9% had a HIV viral load of less than 40 copies/mL and 52.3% had a viral load of at least 200 copies/mL. Of patients who were not receiving ART (n=64), 96.9% had an HIV viral load of at least 200 copies/mL at this time. Stratified by study treatment, the percentage of patients with high HIV viral loads among patients receiving vs not receiving ART was 44.6% and 94.9% for those in the ring group and 70.5% and 100% for those in the placebo group, respectively.

The median CD4+ T-cell count among all patients was 570.0 (range, 199.0-1378.0) and 493.5 (range, 199.0-13780) cells/µL for those receiving and not receiving ART, respectively. Stratified by treatment, the median CD4+ T-cell counts were higher for patients in the ring group who were receiving (605 cells/µL) and not receiving ART (497.0 cells/µL) compared with those in the placebo group receiving (486.0 cells/µL) and not receiving ART (477.0 cells/µL).

Overall, HIV viral load measurements of more than 40 copies/mL were observed among 75.6% of the 78 patients at 6 months after ART initiation, 83.2% of the 95 patients at 12 months after ART initiation, and 73.9% of the 69 patients at 24 months after ART initiation. As with CD4+ T-cell counts, the number of patients who were virologically suppressed at a follow-up visit was increased among those in the ring vs placebo groups.

Overall, the most advanced World Health Organization (WHO)-defined HIV disease stage remained at stage 1 for more than 80% of all patients for the study duration, and staging rates did not differ between those in the ring vs placebo groups.

Among patients with available genotype data (n=147), sequence variations with resistant to any non-nucleoside reverse transcriptase inhibitor (NNRTI) were observed in 16.6%, of which E138A (7.3%), A98G (2.6%), K103N (2.0%), and K101E (1.3%) were the most prevalent. In addition, sequence variations with resistant to any NRTI1 were observed in 1 patient, and 3 patients had sequence variations with resistant to protease inhibitor (PI) treatment. Stratified by treatment arm, the rate of NNRTI-resistant sequence variations was 19.4% for patients in the ring group and 10.4% for those in the placebo group. Of note, all NRTI- and PI-resistance sequence variations were observed among only patients in the ring group.

Limitations include potential selection bias, the use of patient-reported data to determine ART initiation and adherence, and changes in WHO ART guidelines that occurred during the study.

According to the researchers, “These results demonstrate that becoming HIV infected while using the DVR [dapivirine vaginal ring] is unlikely to have any deleterious effect on management of HIV infection in the longer term.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

References:

Steytler J, van der Ryst E, Craig C, et al. Clinical presentation, treatment response and virology outcomes of women who seroconverted in the dapivirine vaginal ring trials – The Ring Study and DREAM. Clin Infect Dis. Published online October 3, 2022. doi:10.1093/cid/ciac804