Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes

Abstract

Background: Multi-class resistance, intolerance, and drug-drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH.

Methods: Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan-Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described.

Results: A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL < 50 copies/mL; 24-month cumulative probability: 80% [95% Confidence Interval 77-82]) than their non-HTE counterparts (85% [84-86]). No difference was observed in the probability of maintaining VLs < 200 copies/mL over the first 48 months after achieving suppression (< 50 copies/mL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cells/µL (24-month cumulative probability: 95% HTE [91-93]; 97% non-HTE [97-97]), and more likely to change regimens (45% HTE; 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5%; deaths 2%) and non-HTE (ADEs 2%; deaths 1%) PLWH.

Conclusions: HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

Keywords: ART; Characteristics; HIV; HTE; Outcomes; Prevalence.

Fig. 1

Inclusion into the study population and study timeline

Fig. 2

Cumulative probability of (a) achieving virologic undetectability to viral load (VL) < 50 copies/mL among viremic people living with HIV (PLWH) (VL ≥ 50 copies/mL) at baseline and (b) maintaining virologic suppression to VL < 200 copies/mL among viremic PLWH at baseline who achieved virologic undetectability (VL < 50 copies/mL) over follow-up

Fig. 3

Cumulative probability of virologic failure (two consecutive viral loads ≥ 200 copies/mL or discontinuation following a viral load ≥ 200 copies/mL) among people living with HIV with a viral load < 50 copies/mL at baseline

Fig. 4

Cumulative probability of maintaining CD4 cell count ≥ 200 cells/µL among people living with HIV with CD4 cell count ≥ 200 cells/µL at baseline