The feasibility of lopinavir/ritonavir (LPV/r) monotherapy as a treatment option in patients failing first-line ART in resource-limited settings remains unclear. Further defining viral response to protease inhibitor monotherapy remains important to help guide recommendations.
This was a prospective, single-arm, non-randomized, open-label, proof-of-concept study evaluating the efficacy of LPV/r mono-therapy over 48 weeks in patients with evidence of treatment failure in Jos, Nigeria. The primary outcome of interest was sustained virologic response(VR) [HIV-1 RNA (VL) <400 copies/mL] measured at monthly intervals.
30 patients were enrolled, with mean VL and CD4 at study entry of 135,549 copies/ml and 274 cells/mL. 28 (93%) achieved VL < 400 of any duration on LPV/r. Mean time to VL < 400 was 7 wks, with mean duration of initial viral suppression of 10 wks. 96% experienced low-level viremia after achieving initial suppression. 73% self-reported adherence of >95% throughout the entire study period.
In the intention to treat(ITT) analysis, only 9 (30%) met the primary outcome of sustained VR until trial completion. The majority of study failures were due to virologic failure (2 consecutive VLs > 1000 ). The mean VL at study failure was 151,554 and occurred at a mean of 22.7 weeks.
In logistic regression, baseline VL and CD4 count were not associated with treatment failure in either group, nor was historic CD4 nadir. A detectable VL (>400) at 12 weeks had a statistically significant association with odds of either ITT failure (OR=8.75, p=0.01) or on treatment failure (OR=6.11, p=0.02), as compared to those who were undetectable. VLs at 24 wks were also strongly predictive of treatment failure at 48 weeks(all with RNA > 400 at 24 wks failed). Resistance was not detected in the virologic failures.
Low-level viremia was common among all patients. LPV/r monotherapy as second-line treatment succeeded in only 30% by ITT criteria. VLs at 12 and 24 weeks were strongly indicative of treatment success at 48 weeks. All patients who had a detectable VL at 24 weeks were ITT failures. These data suggest a high adherence threshold of LPV/r monotherapy. To use this regimen successfully, more intensive adherence interventions are likely needed..
C. Claassen, None