ObjectiveAlthough 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.MethodsHIV-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.ResultsLLV 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).ConclusionsIn 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.

Background 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). Methods We grouped individuals starting cART 1996–2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; &lt;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. Results 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). Conclusions In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.

Background It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of &lt;200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort. Methods People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. Results During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL &lt;200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM. Conclusions Both blips and LLV during ART are associated with increased risk of subsequent VF.

Objectives The clinical significance of low‐level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV‐positive adults in relation to LLV or permanent virological suppression during long‐term ART. Methods Plasma levels of C‐reactive protein (CRP), D‐dimer, vascular cell adhesion molecule 1 (VCAM‐1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF‐15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon‐γ‐induced protein 10 (IP‐10) and β‐2‐microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV‐1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow‐up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t‐test and analysis of covariance (ANCOVA) after logarithmic transformation. Log‐rank analysis was applied for markers with concentration values out of range. Results Compared with controls, patients with LLV had significantly higher levels of GDF‐15 [geometric mean 3416 (95% confidence interval (CI) 804–14 516) pg/mL versus 2002 (95% CI 355–11 295) pg/mL in controls; P = 0.026] and D‐dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t‐test, only GDF‐15 was significantly higher and in the log‐rank test, both GDF‐15 and D‐dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF‐15 and D‐dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.