A single quantifiable viral load is predictive of virological failure in Human Immunodeficiency Virus (HIV)-infected patients on combination antiretroviral therapy: The Austrian HIV cohort study

Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51-199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06-4.55 and HR = 4.21, 95% CI = 2.15-8.22, respectively). In those with VL 51-199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84-5.39 and HR = 2.52, 95% CI = 0.96-6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL

A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997-2000; period 2: 2001-2004; period 3: 2005-2008; period 4: 2009-2011; and period 5: 2012-2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm$^{3}$. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm$^{3}$, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997-2004 and 2005-2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases

Factors associated with low-level viraemia and virological failure: results from the Austrian HIV Cohort Study

BACKGROUND: In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV) and virological failure (VF) under combined antiretroviral therapy (cART). MATERIALS AND METHODS: We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL) measurement below the quantification limit (BLQ) in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models. RESULTS: Of 2276 participants, 1972 (86.6%) were BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI): 4.19 (2.07-8.49); for 10.000-99.999 copies/mL: aOR (95% CI): 2.52 (1.23-5.19)] and shorter cART duration [for <9 months: aOR (95% CI): 2.59 (1.38-4.86)]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI): 2.76 (1.03-7.35); for 30-50 years: aOR (95% CI): 2.70 (1.26-5.79)], people originating from high prevalence countries [aOR (95% CI): 2.20 (1.09-4.42)] and in male injecting drug users [aOR (95% CI): 2.72 (1.38-5.34)]. CONCLUSIONS: For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration

Characteristics of patients stratified by HIV RNA levels below the limit of quantification and low-level viraemia defined as quantifiable HIV RNA levels <200 copies/mL and virological failure defined as HIV RNA levels ≥200 copies/mL.

<p>Abbreviations: LLV, low-level viraemia; VF, virological failure; VL, viral load; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI/r, boosted protease inhibitor; INSTI, integrase inhibitor; BLQ, below the limit of quantification; cART, combination antiretroviral therapy;</p><p>¹ Comparison between quantifiable HIV RNA levels <200 copies/mL (LLV) and HIV RNA levels below the limit of quantification (BLQ).</p><p>² Comparison between HIV RNA levels ≥200 copies/mL (VF) and HIV RNA levels below the limit of quantification (BLQ).</p><p>³ Interruptions prior to 6 months stable cART of the respective cART regimen.</p><p>⁴ Diabetes mellitus prior to 6 months stable cART of the respective cART regimen.</p><p>⁵ cART duration until 6 months stable cART of the respective cART regimen.</p><p>⁶ Whether the respective cART regimen is a first-line cART or not.</p><p>Characteristics of patients stratified by HIV RNA levels below the limit of quantification and low-level viraemia defined as quantifiable HIV RNA levels <200 copies/mL and virological failure defined as HIV RNA levels ≥200 copies/mL.</p

Univariable and multivariable logistic regression results: Association between different factors and low-level viraemia as well as virological failure compared to HIV RNA levels below the limit of quantification.

<p>Abbreviations: LLV, low-level viraemia; VF, virological failure; VL, viral load; CI, confidence interval; OR, odds ratio; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI/r, boosted protease inhibitor; INSTI, integrase inhibitor; cART, combination antiretroviral therapy;</p><p>¹ Interruptions prior to 6 months stable cART of the respective cART regimen.</p><p>² Diabetes mellitus prior to 6 months stable cART of the respective cART regimen.</p><p>³ cART duration until 6 months stable cART of the respective cART regimen.</p><p>⁴ Whether the respective cART regimen is a first-line cART or not.</p><p>Univariable and multivariable logistic regression results: Association between different factors and low-level viraemia as well as virological failure compared to HIV RNA levels below the limit of quantification.</p

AIDS

OBJECTIVE: Hepatitis C Virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS non-liver (NANL) cancers between HCV co-infected PWH who reached SVR and mono-infected PWH. DESIGN: Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at time of ART initiation. METHODS: Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (HR) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. RESULTS: Among 62,495 PWH, 2,756 acquired HCV, of whom 649 reached SVR. For 582 of these, ≥1 mono-infected PWH could be matched, producing a total of 5,062 mono-infected PWH. The estimated HRs comparing HCV co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95%CI 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. CONCLUSION: PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared to mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV co-infected PWH who reached SVR after a DAA-based treatment compared to mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR