The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies

Abstract

Background: HIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.

Methods: Posttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers.

Results: Of the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years.

Conclusions: Posttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission.

Figures

Figure 1.

Changes in CD4+ cells in the initial 24 weeks of treatment interruption in posttreatment controllers (PTCs) versus noncontrollers (NCs). Boxes depict median and interquartile range; whiskers show the 5th and 95th percentile. Dots represent all data not contained within the whiskers. The open blue circle depicts a value of −2163 cells/mm3.

Figure 2.

Highest viral load in posttreatment controllers (PTCs) versus noncontrollers (NCs) over the first 24 weeks of treatment interruption. A, Early viral load peak levels in PTCs versus NCs, also categorized by timing of ART initiation. B, The week of treatment interruption at which an early detectable viral load peak occurred. Boxes depict median and interquartile range; whiskers show the 5th and 95th percentile. Dots represent all data not contained within the whiskers. PTCs with ambiguous timing of ART start were excluded from the analysis that categorized PTCs by early versus chronic ART initiation (3 and 1 participants for A and B, respectively).

Figure 3.

Early viral load peaks during the first 24 weeks of treatment interruption. Proportion of posttreatment controllers (PTCs) (A) and posttreatment noncontrollers (NCs) (B) categorized by viral load peak. C, Proportion of viral load peaks in the PTCs and NCs for participants with weekly versus less frequent viral load measurements. P value represents Fishers exact test of PTCs with viral load peak ≥10000 HIV-1 RNA copies/mL with weekly viral load measurement versus less frequent monitoring. For NCs, the comparison is for the proportion with viral load peak ≥100000 HIV-1 RNA copies/mL. Abbreviation: Cp/mL, HIV-1 RNA copies/mL.

Figure 4.

Rate of viral load decay in posttreatment controllers (PTCs) versus 3 comparator groups. Viral decay rates per day were compared between PTCs versus 3 comparator groups: (1) posttreatment noncontrollers (NCs) after treatment interruption, (2) antiretroviral therapy (ART)-naive participants during natural acute infection, and (3) phase 1 and 2 decay rates in participants initiating first-line nonnucleoside reverse transcriptase inhibitor-based ART from 2 previously published ACTG trials [27, 28].

Figure 5.

Durability of viral control. The solid line depicts the point estimates for the proportion of posttreatment controllers (PTCs) who maintained viral control at each time point. In the numbers under the X axis, the numerator represents PTCs who maintained viral control and the denominator are all PTCs with available data through this time point or were known to have lost viral control prior to this time point. Uncertainty around the point estimates is depicted by an upper and lower bound (dotted lines). For each time point, the upper bound is calculated by assuming that all participants who did not have virologic data maintained HIV control and the lower bound assumed that they had all lost viral control.