Low-level HIV viraemia during antiretroviral therapy: Longitudinal patterns and predictors of viral suppression.

OBJECTIVES: Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low-level viraemia (LLV) during antiretroviral therapy (ART). METHODS: We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51-199 copies/mL 30-365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression. RESULTS: Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow-up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2-2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0-2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log10 copies/mL; 95% CI 0.37-0.89), injecting drug use (aOR 0.67; 95% CI 0.47-0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49-0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32-0.85). CONCLUSION: Most people with LLV did not experience sustained viral suppression during 24-month follow-up, supporting the association between LLV and inferior treatment outcome.

Is low-level HIV-1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

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 ß-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.