Efficacy and safety by baseline HIV-RNA and CD4 count in treatment-naive patients treated With atazanavir/r and lopinavir/r in the CASTLE study

Purpose of the study

In the CASTLE study, lower response rates were observed in patients with baseline HIV-RNA ≥100,000 copies/mL in both arms and were associated with lower baseline CD4 cell count for LPV/r but not ATV/r.

Methods

Randomized, open-label, prospective study comparing once-daily ATV/r with twice-daily LPV/r, both with fixed-dose TDF/FTC in 883 treatment-naive patients. Treatment outcomes of HIV-RNA <50 c/mL at week 48 using confirmed virologic response (CVR) and grade 2–4 treatment-related AEs through week 48 are presented by pre-specified baseline HIV-RNA and CD4 cell count strata.

Summary of results

The proportion of responders (CVR HIV-RNA <50 c/mL, ITT) at week 48 by baseline HIV RNA strata (<100,000, 100,000–<500,000, and ≥500,000) were 83%, 76%, and 64% for ATV/r and 80%, 74%, and 61% for LPV/r (Table 1).

Table 1 CVR Treatment Outcomes of HIV RNA <50 c/mL at Week 48 by Baseline CD4 Cell Count, n (%).

In patients with both baseline CD4 <100 and HIV-RNA ≥100,000, 60/83 (72%) on ATV/r and 40/64 (63%) on LPV/r achieved HIV RNA <50 c/mL (CVR, ITT). Incidence of grades 2–4 treatment-related AEs through week 48 by baseline HIV-RNA strata (<100,000, 100,000–<500,000, and ≥500,000) were 29%, 26%, and 15% for ATV/r; and 31%, 27%, and 30% for LPV/r. (Table 2.)

Table 2 Grade 2–4 Treatment-Related AEs through Week 48 by Baseline CD4 Cell Count (cells/mm3), n (%).

Conclusion

Lower response rates at higher baseline HIV-RNA were seen for both ATV/r and LPV/r. The trend for lower response rates at lower baseline CD4 cell counts for LPV/r observed in the ITT analysis did not appear to be present in the on-treatment analysis. ATV/r and LPV/r had consistent adverse event (AE) profiles within each arm by baseline HIV-RNA. More AEs, most commonly diarrhea and nausea, were observed with LPV/r at low baseline CD4 cell counts.