Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

Abstract

Objective: Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.

Methods: HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner.

Results: LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09).

Conclusions: In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

Fig 1. Flowchart of patient inclusion and exclusion.

Abbreviations: ART–Antiretroviral treatment.

Fig 2. Flowchart illustrating patients changing viremia categories during follow-up.

The top of the figure represents viremia categories at inclusion and the lower part shows how patients changed categories during the follow-up time. Reclassification was only made to higher viremia strata, and the reclassified subjects remained in that strata for the remaining follow-up period (unless progression to a higher viremia stratum occurred). Abbreviations: PSV–permanently suppressed viremia; LLV-I–low-level viremia 50–199 copies/mL; LLV-II–low-level viremia 200–999 copies/mL; HLV–high-level viremia.

Fig 3. Extended Kaplan-Meier estimate for virological failure, stratified by viremia category (n = 992).

Abbreviations: PSV–permanently suppressed viremia; LLV-I–low-level viremia 50–199 copies/mL; LLV-II–low-level viremia 200–999 copies/mL; HLV–high-level viremia.

Fig 4. Extended Kaplan-Meier plot for death stratified by viremia category (n = 1015).

Abbreviations: PSV–permanently suppressed viremia; LLV-I–low-level viremia 50–199 copies/mL; LLV-II–low-level viremia 200–999 copies/mL; HLV–high-level viremia.