Reduced adherence to antiretroviral therapy is associated with residual low-level viremia (original) (raw)
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Predictors of residual viremia in patients on long-term suppressive antiretroviral therapy
Antiviral Therapy, 2012
Background HIV-1-infected individuals with plasma RNA<50 copies/ml on antiretroviral therapy (ART) may have residual, low-level viraemia detectable by PCR assays that are able to detect a single copy of viral RNA (single-copy assay [SCA]). The clinical predictors of residual viraemia in patients on long-term suppressive ART are not yet fully understood. Methods We evaluated factors associated with residual viraemia in patients on suppressive ART who underwent screening for a raltegravir intensification trial (ACTG A5244). The screened population was HIV-1-infected adults receiving ART for ≥12 months with pre-ART HIV-1 RNA>100,000 copies/ml and on-therapy RNA levels below detection limits of commercial assays for ≥6 months. Results Of 103 patients eligible for analysis, the median age was 46 years and the median duration of viral suppression was 4.8 years. 62% had detectable viraemia (>0.2 copies/ml) by SCA (median 0.2 copies/ml, IQR <0.2–1.8). Younger patients had lower ...
AIDS Patient Care and STDs, 2007
Data from 197 patients for whom highly active antiretroviral therapy (HAART) failed, who started a new regimen chosen under the guide of resistance testing results interpreted by experts, were retrospectively studied, provided that at least 2 determinations of adherence and plasma drug concentrations were performed during the follow-up. Univariate and multivariable logistic regression analyses were conducted, using confirmed virologic response at week 24 as outcome measure (i.e., achievement of undetectable HIV plasma viral load at any time point before week 24 and its maintenance up to week 24). Suboptimal drug concentrations (odds ratio [OR]: 0.3; 95% confidence interval [CI] 0.2-0.7; p ؍ 0.006) and suboptimal adherence (OR: 0.4; 95% CI 0.2-0.8; p ؍ 0.014) were both negative independent predictors of sustained virologic response, while the use of boosted protease inhibitor-containing regimens resulted to be protective (OR: 2.4; 95% CI 1.1-5.3; p ؍ 0.032).
AIDS Research and Human Retroviruses, 2015
Objective: Aim of this study was to evaluate the impact of HIV-1 very low level viremia (<50 copies/ml) on the 2-year risk of virological failure. Methods: A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/mL (outpatient clinic in Italy, first semester of 2010) was performed. HIV RNA was measured through real time Polymerase Chain Reaction (PCR) assay CAP/CTM HIV-1 version 2.0 (detection limit: 20 copies/mL) and stratified as undetectable RNA ("Target Not Detected", TND), <20 copies/mL, 20-50 copies/mL. After 96 weeks virological failure was defined as two consecutive viral loads above 50 copies/mL. Log-rank tests and a multivariate Cox proportional hazard model were used for uni-and multivariate analysis. Results: 1055 patients (71.4% male, 87.4% Caucasian, aged 46.7 years) were included: nadir and current CD4 cell count were 203 cells/mm 3 (106-292) and 554 cells/mm 3 (413-713.5). HIV RNA was undetectable in 781 patients (74%), <20 copies/mL in 190 patients (18%) and 20-50 copies/mL in 84 patients (8%). Virological failure was observed in 81 patients (7.7%); at multivariate analysis detectable RNA at baseline (p=0.017), HCV infection (p=0.020), more than 3 pills in the regimen (p=0.003) and duration of HIV RNA<50 copies/mL below 2 years (p<0.001) were independently associated with virological failure. In 14 patients newly selected resistance-associated mutations were observed. Conclusions: Undetectable HIV RNA by real-time PCR is significantly associated with a lower 2year risk of virological failure along with Ab HCV-negativity, longer viral control and lower pill burden. Studies investigating the management of residual viremia under antiretroviral treatment are warranted.
The Journal of Infectious Diseases, 2007
Background. To identify potential causes and clinical implications of transient increases in plasma viral load (hereafter, "blips"). Methods. M99-056 and M02-418 were prospective, randomized trials evaluating the safety and efficacy of lopinavir/ritonavir (LPV/r) capsules administered twice per day or once per day to subjects infected with human immunodeficiency virus-1 (HIV-1). Plasma viral load was measured every 4 weeks (from baseline through week 24, excluding week 12 and week 20 in M02-418), every 8 weeks (from week 24 through week 48), and every 12 weeks (from week 48 through week 96). Blips were defined by 1 plasma viral load measurement of between 50-1000 copies/mL, immediately preceded and immediately followed by a measurement of Ͻ50 copies/mL. A medication event monitoring system was used to record the date and time subjects administered a dose of LPV/r. Results. Of 228 subject enrolled, event monitor data were available for 223 (98%) subjects (92 of whom received twice-daily LPV/r therapy, and 131 of whom received once-daily therapy). Viral load blips (median plasma viral load, 82 copies/mL [range, 51-858 copies/mL]) were identified in 60 (27%) of the subjects (21 in the LPV/r twice-daily group and 39 in the LPV/r once-daily group). Neither the baseline plasma viral load nor the CD4 ϩ T cell count were associated with blips. During the week prior to a blip, the mean number of days that the subject administered the prescribed number of doses was lower than the number during a matched period for the same subject during which a blip did not occur (5.55 vs. 6.22 days; P ϭ .007). Blips were not associated with virologic failure or the development of drug resistance. Conclusions. Blips were associated with decreased adherence, but not with virologic failure or development of drug resistance in these studies of LPV/r. Trial registration. Clinicaltrials.gov identifier: NCT00043966. "Blips" are defined as intermittent episodes of detectable, low-level increases in plasma HIV-1 RNA (ie, viral load), which return spontaneously to an undetectable range without any change in treatment. Blips are observed frequently in HIV-1-infected individuals who re
AIDS Research and Human Retroviruses, 2008
The relationship between adherence, antiretroviral regimen, and viral load (VL) suppression was assessed through a 1 year prospective follow-up study among 1142 HIV-infected patient. Patients on antiretroviral therapy who attended to the pharmacy during a 6-month period were considered eligible. Those included in the final analysis were patients who had been taking the same antiretroviral therapy for Ն6 months since their inclusion. The cohort included patients taking first line therapy (n ϭ 243) and antiretroviral-experienced patients (n ϭ 899). Naive patients who were included had to have reached undetectable VL at enrollment. Antiretroviral-experienced patients with detectable VL determinations in the previous 6 months were excluded. Adherence was measured by means of announced pill counts and dispensation pharmacy records. Of patients, 58% were taking NNRTI, 31.4% boosted PI, and 10.6% unboosted PI-based regimens. Overall, the relative risk of virologic failure was 9.0 (95% CI 4.0-20.1) in patients with adherence 80-89.9%, 45.6 (95% CI 19.9-104.5) with adherence 70-79.9%, and 77.3 (95% CI 34.2-174.9) with adherence Ͻ70%, compared with adherence of Ն90%. The risk of virologic failure in patients with adherence Ͻ90% taking unboosted PI was 2.5 times higher than the group taking boosted PI (95% CI 1.2-5.3). There were no statistical differences in patients taking boosted PI and those who were taking NNRTI. Less than 95% of adherence is associated with high virologic success. For patients taking NNRTI-or boosted PI-based regimens with adherence rates of 80%, the failure rate is Ͻ10%. These data do not affect the goal of achieving the highest level of adherence possible.
Aids Research and Human Retroviruses, 2008
We evaluated the association between two antiretroviral therapy (ART) adherence measurements-the medication possession ratio (MPR) and patient self-report-and detectable HIV viremia in the setting of rapid service scale-up in Lusaka, Zambia. Drug adherence and outcomes were assessed in a subset of patients suspected of treatment failure based on discordant clinical and immunologic responses to ART. A total of 913 patients were included in this analysis, with a median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had optimal adherence (MPR Ն95%), 306 (34%) had suboptimal adherence (MPR 80-94%), and 76 (8%) had poor adherence (MPR Ͻ80%). Of the 913 patients, 238 (26%) had VL Ն400 copies/ml when tested. When compared to individuals with optimal adherence, there was increasing risk for virologic failure in those with suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based on MPR. During the antiretroviral treatment course, 676 patients (74%) reported no missed doses. The proportion of patients with virologic failure did not differ significantly among those reporting any missed dose from those reporting perfect adherence (26% vs. 26%, p ϭ 0.97). Among patients with suspected treatment failure, a lower MPR was associated with higher rates of detectable viremia. However, the suboptimal sensitivity and specificity of MPR limit its utility as a sole predictor of virologic failure.
HIV Medicine, 2010
The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients. Methods The analysis was performed on the Royal Free HIV Cohort, London, UK. Each 'drug coverage-viral load episode' (DCVL episode) was defined as a 6-month period immediately prior to a VL 50 HIV-1 RNA copies/mL (time-zero), during which the patient had been continuously on HAART, with all measured VLs 50 copies/mL. The next VL after time-zero was used to assess whether VL rebound (defined as 4200 copies/mL) had occurred. Drug coverage, our measure of adherence, was calculated as the proportion of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs. Results A total of 376 (2.4%) VL rebounds occurred in 15 660 DCVL episodes among 1632 patients. Drug coverage was 100% for 32% of episodes, 95-99% for 16% of episodes and 60% for 10% of episodes. The risk ratio of rebound associated with a 10% increase in drug coverage, adjusted for potential confounding variables, was 0.93 (95% confidence interval 0.88-0.98). Conclusions Antiretroviral drug coverage assessed at the time of VL measurement in patients with undetectable VL is potentially clinically useful for predicting VL rebound at the next VL measurement.