Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection

Abstract

Objective: Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI).

Design: This was a prospective, single-arm evaluation of once-daily, co-formulated emtricitabine/tenofovir/efavirenz initiated during AHI.

Methods: The primary endpoint is the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression and CD8 cell activation in relation to baseline participant characteristics. We compared time to viral suppression and viral dynamics using linear mixed-effects models between acutely infected participants and chronically infected controls.

Results: Between January 2005 and May 2009, 61 AHI participants were enrolled. Of participants whose enrollment date allowed 24 and 48 weeks of follow-up, 47 of 51 (92%) achieved viral suppression to less than 200 copies/ml by week 24, and 35 of 41 (85.4%) to less than 50 copies/ml by week 48. The median time from ART initiation to suppression below 50 copies/ml was 93 days (range 14-337). Higher HIV RNA levels at ART initiation (P = 0.02), but not time from estimated date of infection to ART initiation (P = 0.86), were associated with longer time to viral suppression. The median baseline frequency of activated CD8+CD38+HLA-DR+ T cells was 67% (range 40-95), and was not significantly associated with longer time to viral load suppression (P = 0.15). Viremia declined to less than 50 copies/ml more rapidly in AHI than chronically infected participants. Mixed-model analysis demonstrated similar phase I HIV RNA decay rates between acute and chronically infected participants, and more rapid viral decline in acutely infected participants in phase II.

Conclusion: Once-daily emtricitabine/tenofovir/efavirenz initiated during AHI achieves rapid and sustained HIV suppression during this highly infectious period.

Conflict of interest statement

Potential Financial Conflicts of Interest: C.G. has received research support from Bristol Myers Squibb, Gilead Sciences, Abbott and Tibotec Therapeutics. C.H. has received grant support and/or consulting/honoraria from BMS, GSK, Merck, Tibotec, Gilead, Myriad Pharmaceuticals, Pfizer. D.M. has received research support from Bristol Myers Squibb, Gilead Sciences, Merck, Abbott, and Roche, and is a honoraria for professional services to Bristol Myers Squibb, Merck, Chimerix, and Tibotec Therapeutics. J.E. receives research support from Merck and GlaxoSmithKline and is a consultant to Bristol Myers Squibb, Merck, and Tibotec Therapeutics. A.M., A.B., J.K., K.M., M.K., S.F., G.F. - No conflicts.

Figures

Figure 1

Time to viral load suppression among acutitely-infected participants who initiated antiretroviral therapy during acute HIV infection compared with chronically infected patients starting an efavirenz-based regimen. The black line in Figure 1A shows the time-to-viral-suppression to <50 copies/mL among all acutely infected participants started on antiretroviral therapy during the acute period. The blue and red lines show the time-to-viral-suppression <50 copies/mL stratified by baseline HIV RNA levels among acutely-infected subjects who started antiretroviral therapy. Figure 1B shows the comparison of time-to-viral-suppression with a NNRTI-based regimen between participants starting antiretroviral therapy during acute HIV infection and chronically-infected participants starting treatment during established HIV infection.

Figure 1

Time to viral load suppression among acutitely-infected participants who initiated antiretroviral therapy during acute HIV infection compared with chronically infected patients starting an efavirenz-based regimen. The black line in Figure 1A shows the time-to-viral-suppression to <50 copies/mL among all acutely infected participants started on antiretroviral therapy during the acute period. The blue and red lines show the time-to-viral-suppression <50 copies/mL stratified by baseline HIV RNA levels among acutely-infected subjects who started antiretroviral therapy. Figure 1B shows the comparison of time-to-viral-suppression with a NNRTI-based regimen between participants starting antiretroviral therapy during acute HIV infection and chronically-infected participants starting treatment during established HIV infection.

Figure 2

Estimates of log10HIV RNA from a nonlinear mixed model from 0 to 11 months following ART initiation among acutely- and chronically-infected participants with one inflection point at 10 days.

Figure 3

Figure 3A shows immune activation dynamics among acutely-infected participants from the time of antiretroviral initiation. Figure 3B compares levels of immune activation among acutely-infected individuals by time since antiretroviral initiation with a seronegative cohort.

Figure 3

Figure 3A shows immune activation dynamics among acutely-infected participants from the time of antiretroviral initiation. Figure 3B compares levels of immune activation among acutely-infected individuals by time since antiretroviral initiation with a seronegative cohort.