Lower Incidence of HIV-1 Blips Observed During Integrase Inhibitor–Based Combination Antiretroviral Therapy

Suzan Dijkstra, MD; L. Marije Hofstra, MD, PhD; Tania Mudrikova, MD, PhD; Annemarie M. J. Wensing, MD, PhD; Patrick G. A. Oomen, MD; Andy I. M. Hoepelman, MD, PhD; Berend J. van Welzen, MD, PhD

Disclosures

J Acquir Immune Defic Syndr. 2022;89(5):575-582. 

In This Article

Results

Study Population

A total of 2056 PLWH with VL measurements in the study period were assessed, and 1661 were eligible for analysis (Figure 1). After a review of the physicians' documented conclusion on treatment adherence, PI-based treatment courses were more likely to be excluded based on documented nonadherence than were other courses (9.1% versus 3.2%; P < 0.001). No difference in documented nonadherence was found between NNRTIs and INSTIs (3.4% versus 3.0%; P = 0.549). All 3405 eligible treatment courses were analyzed, resulting in a total of 8902 person-years of follow-up including 24,081 VL measurements after the initial VL < 50 copies/mL required for virologic suppression. The mean duration of treatment follow-up was 2.6 years. PI-based treatment courses were the most frequent (n = 1275; 37.4%), followed by NNRTI-based (n = 1121; 32.9%) and INSTI-based courses (n = 1009; 29.6%) (see Table S1, Supplemental Digital Content 1, https://links.lww.com/QAI/B780 for specifications of the drugs used as anchor, NRTI backbone, and booster). The demographic and clinical characteristics of all PLWH and subgroups with the different ART combinations are presented in Table 1. The included PLWH were predominantly men (n = 1343; 80.9%), and the mean age at start of follow-up was 43.4 years. Baseline characteristics differed between the 3 cART groups. Follow-up of the 3405 analyzed treatment courses most commonly ended because of regimen switches (n = 1694; 49.8%) or ending of the study period (n = 1263; 37.1%).

Figure 1.

Flowchart of identification of eligible PLWH and treatment courses.

Correlates of Viral Blips

Throughout the follow-up period, a total of 308 blips occurred in 247 PLWH (14.9% of the study cohort). Overall blip incidence rate was 3.46/100 person-years of follow-up. Most of the PLWH experienced 1 blip (n = 199; 80.6%), 38 PLWH experienced 2 nonconsecutive blips (15.4%), and 10 PLWH experienced 3 or more blips (4.0%). The blip VL ranged from 50 to 496 copies/mL (mean 114). Most blips were of low level (ie, 50–199 copies/mL) (n = 268; 87.0%). Blips that occurred during treatment with NNRTI-based or INSTI-based treatment courses had a significantly higher mean VL than blips that occurred during PI-based courses (Figure 2). No differences in blip rates were found when the different drugs within the anchor groups were compared (see Table S2, Supplemental Digital Content 2, https://links.lww.com/QAI/B780 for within-anchor group comparisons).

Figure 2.

Scatterplot of blip viral load by cART anchor. Horizontal black lines represent the mean values. P values are indicated for each pairwise comparison of the mean values (the Mann–Whitney U test).

The number of blip occurrences per cART anchor was 124 for NNRTIs, 147 for PIs, and 37 for INSTIs, accounting for 3.22, 4.67, and 1.95 blips per 100 person-years of follow-up, respectively. In unadjusted negative binomial models, significant associations with blips were cART anchor, age at diagnosis, time since ART initiation, zenith VL, and VL test frequency (Table 2). These factors, together with Fiebig stage, lowest available CD4+ count, and sex, were included in the multivariable model. When compared with NNRTI-based treatment courses, the incidence of blips was significantly higher during the use of PI-based courses (IRR 1.37; 95% CI: 1.05 to 1.78; P = 0.020) and significantly lower during INSTI-based courses (IRR 0.64; 95% CI: 0.43 to 0.96; P = 0.029). Higher zenith VL, shorter time since ART initiation, and higher VL test frequency were significant correlates of blips as well. Results remained consistent in several sensitivity analyses that were performed (see Table S3–S7, Supplemental Digital Content 3, https://links.lww.com/QAI/B780 for results of the sensitivity analyses). Twenty treatment courses (0.6%) ended with a single VL 50–499 copies/mL immediately before anchor switch and were censored at the last undetectable VL because the VL elevation did not meet the blip criterion regarding anchor changes. Their clinical characteristics did not differ from the other courses (see Table S8, Supplemental Digital Content 4, https://links.lww.com/QAI/B780 for clinical characteristics of PLWH that switched anchor after a single VL 50–499 copies/mL), and counting these elevations as blips did not significantly change the results (see Table S6, Supplemental Digital Content, https://links.lww.com/QAI/B780).

PLLV and Virologic Failure

PLLV occurred in 65 cases and virologic failure in 37 cases. PLWH experiencing blips were more likely to demonstrate PLLV at some point during follow-up (IRR 2.62; 95% CI: 1.57 to 4.38; P < 0.001), but no association with virologic failure was found (IRR 0.84; 95% CI: 0.35 to 1.99; P = 0.684). Occurrence of a blip was not associated with an increased rate of subsequent PLLV or virologic failure within that same treatment course (P ≥ 0.193). PLLV was encountered more frequently during PI-based cART than during NNRTI-based cART (IRR 3.24; 95% CI: 1.76 to 5.96; P < 0.001) and INSTI-based cART (IRR 2.90; 95% CI: 1.31 to 6.45; P = 0.009). No difference was found in this regard between NNRTIs and INSTIs (P = 0.804). The occurrence of virologic failure did not differ significantly between the studied anchors (P ≥ 0.544). Furthermore, no different rates of PLLV and virologic failure were found when comparing PLWH experiencing moderate-level blips with PLWH experiencing none or only low-level blips (P ≥ 0.120).

Clinical Burden

The mean time between a blip and the following VL measurement was 11.2 weeks (11.8 and 7.7 weeks for low-level and moderate-level blips, respectively), compared with 19.0 weeks in PLWH without blips (P < 0.001). In 10 years, the 308 blips led to a total of 165 extra VL measurements, 189 extra telephonic consultations, 37 extra outpatient visits, 34 drug level measurements, 1 lumbar puncture to exclude viral escape in the central nervous system, and 1 hospital admission for a 24-hour pharmacokinetic curve.

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