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

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.