Control of HIV viral load (VL) is effective prevention of perinatal transmission. Antiretroviral therapies (ART) include nucleoside reverse transcriptase inhibitors (NRTIs), but these can have side effects in the fetus. We evaluated a strategy with no NRTI during pregnancy, intrapartum and post-partum prophylaxis in women at low risk of HIV perinatal transmission. Our objective was to estimate, in women switching to darunavir/ritonavir monotherapy (DRV/r) early in pregnancy, the proportion maintaining a VL < 50 copies/mL at delivery, with no need of treatment reintensification.
A one-arm, open-label, phase 2 clinical trial was performed in 24 French centers. Women with virological suppression and CD4 ? 250 cells/?L were enrolled to treatment simplification with DRV/r (600/100 mg bid) in the 1st trimester of pregnancy. Plasma VL was monitored monthly and ART was reintensified in case of viral rebound (>50 copies/mL). Tolerance issues were managed per usual guidelines. Neonates received prophylaxis with nevirapine qd for 14 days. The trial was designed to investigate the virological success rate, with a 2-sided alpha=5% for the exact test comparing the observed proportion of VL<50 copies/mL on monotherapy against a minimum success rate set at p0=85% and an expected success rate of p1=95%, requiring 80 evaluable patients.
Of 91 women enrolled, 89 switched to DRV/r monotherapy ; 83 were evaluable, 4 miscarried before 22 weeks’ gestation, and 2 changed because of elevated liver enzymes. Treatment was reintensified with NRTIs for viral rebound in ¬6/83 (median VL 193 copies/mL; range 78-252), including 2 patients whose rebound occurred on triple ART after screening but before switching to DRV/r. Another 2 patients with VL missing at delivery were considered as failures in the primary per-protocol analysis, resulting in a success rate of 75/83, 90.4% (95%CI, 81.9-95.7%), not significantly above p0=85% (p=0.22). The 2 patients with missing delivery VL had undetectable values on DRV/r until 33 days and 13 days before delivery. If considering them as successes, success was 77/83 = 92.8% (95%CI, 84.9-97.3%), which was significantly higher than 85% (p=0.045). In an intent-to-treat analysis, all 89 women who switched to DRV/r monotherapy had their last VL before delivery < 50 copies/mL. There was no case of perinatal HIV transmission.
This pilot study suggests that a NRTI-free strategy with careful viral load surveillance can maintain viral suppression during pregnancy.