All-Cause Mortality and Serious Non-AIDS Events in Adults With Low-level Human Immunodeficiency Virus Viremia During Combination Antiretroviral Therapy: Results From a Swedish Nationwide Observational Study

Abstract

The impact of low levels of human immunodeficiency virus (HIV) RNA (low-level viremia [LLV]) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAEs). We grouped individuals starting cART 1996–2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load, 50–999 copies/mL), and nonsuppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50–199 and 200–999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes. A total of 6956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.3–3.6). This association was also observed for LLV 50–199 copies/mL (aHR, 2.2; 95% CI, 1.3–3.8), but was not statistically significant for LLV 200–999 copies/mL (aHR, 2.1; 95% CI, .96–4.7). LLV 50–999 copies/mL was not linked to increased risk of AIDS or SNAEs, but in subanalysis, LLV 200–999 copies/mL was associated with SNAEs (aHR, 2.0; 95% CI, 1.2–3.6). In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.