True Durability: HIV Virologic Suppression in an Urban Clinic and Implications for Timing of Intensive Adherence Efforts and Viral Load Monitoring (original) (raw)
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Open Forum Infectious Diseases, 2023
Background: Antiretroviral therapy (ART) is recommended for people with HIV (PWH), irrespective of CD4 cell count, to improve their health and reduce the risk of transmission to sexual partners through long-term viral suppression. We identified risk factors for viral rebound among patients with a period of stable viral suppression to inform counseling and monitoring. Methods: We conducted a multi-site, retrospective study of PWH with a two-year period of sustained viral suppression in the United States using the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We used multivariable logistic regression to identify characteristics independently associated with any viral rebound [viral load (VL) ≥200 copies/mL] and sustained viral rebound (VL ≥200 copies/mL followed by a VL that was also ≥200 copies/mL within six months), within two years of follow-up. Results: Among 3,496 eligible patients with a two-year period of sustained viral suppression, most (90%) continued to have viral suppression over two additional years; 10% experienced viral rebound, and 4% experienced sustained viral rebound. In multivariable analyses, Black race, current smoking, integrase strand transfer inhibitor use, and five-to-nine-year duration of ART were positively associated, and being age ≥50 years was negatively associated, with any viral rebound. Only current smoking and five-to-nine-year (vs. two-to-four-year) duration of ART were positively associated, and being age ≥60 years was negatively associated, with sustained viral rebound. Conclusions: Most people retained in clinical care and with HIV viral suppression on ART will have persistent viral suppression. However, some patients may benefit from additional treatment adherence supports.
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.
AIDS Patient Care and STDs, 2005
Clinical trials commonly measure rates of virologic suppression at a specific time point, whereas sustained virologic suppression is the goal of highly active antiretroviral therapy (HAART). We explored factors associated with sustained virologic suppression in an urban clinic population. The study population was drawn from patients who enrolled in Montefiore Medical Center's Infectious Diseases Clinic from 1999 to 2000. A computerized query of the hospital information system generated a list of potential case patients having every HIV-1 viral load (VL) less than 50 copies per milliliter throughout 2002 (at least three VL measurements were required), and a list of potential controls who failed to demonstrate sustained virologic suppression during 2002. Demographic and clinical information were collected by chart review, and case and control patient characteristics were compared by both univariate and multivariate analyses. Sixty-four case patients were compared to 64 controls. There were no significant differences in age, gender, ethnicity, type of antiretroviral therapy, or frequency of clinic visits. During the year of the study, cases experienced a significantly greater rise in CD4 ؉ lymphocyte counts than controls (108 cells per microliter versus 27 cells per microliter). On univariate analysis, factors associated with sustained virologic suppression included risk behavior other than heterosexual contact or injection drug use, being a non-smoker, and hepatitis C seropositivity. On logistic regression analysis, factors independently associated with sustained virologic suppression were risk behavior other than heterosexual contact or injection drug use (IDU), and hepatitis C seropositivity. In this study sample, being a nonsmoker, having a risk behavior for HIV acquisition other than heterosexual contact or IDU, and being seropositive for hepatitis C were associated with sustained virologic suppression. Computerized query of the hospital information system proved to be a powerful tool for the identification of study patients in a real-world clinic environment.
Predictors of Antiretroviral Treatment Failure in an Urban HIV Clinic
Journal of Acquired Immune Deficiency Syndromes, 2007
Background-Predictors of antiretroviral treatment (ART) failure are not well characterized for heterogeneous clinic populations. Methods-A retrospective analysis was conducted of HIV-infected patients followed in an urban HIV clinic with an HIV RNA measurement ≤400 copies/mL on ART between January 1, 2003, and December 31, 2004. The primary endpoint was treatment failure, defined as virologic failure (≥1 HIV RNA measurement >400 copies/mL), unsanctioned stopping of ART, or loss to follow-up. Prior ART adherence and other baseline patient characteristics, determined at the time of the first suppressed HIV RNA load on or after January 1, 2003, were extracted from the electronic health record (EHR). Predictors of failure were assessed using proportional hazards modeling. Results-Of 829 patients in the clinic, 614 had at least 1 HIV RNA measurement ≤400 copies/mL during the study period. Of these, 167 (27.2%) experienced treatment failure. Baseline characteristics associated with treatment failure in the multivariate model were: poor adherence (hazard ratio [HR] = 3.44; 95% confidence interval [CI]: 2.34 to 5.05), absolute neutrophil count <1000/mm 3 (HR = 2.90, 95% CI: 1.26 to 6.69), not suppressed on January 1, 2003 (HR = 2.69, 95% CI: 1.78 to 4.07) or <12 months of suppression (HR = 1.64, 95% CI: 1.10 to 2.45), CD4 count <200 cells/mm 3 (HR = 1.90, 95% CI: 1.31 to 2.76), nucleoside-only regimen (HR = 1.75, 95% CI: 1.08 to 2.82), prior virologic failure (HR = 1.70, 95% CI: 1.22 to 2.39) and ≥1 missed visit in the prior year (HR = 1.56, 95% CI: 1.13 to 2.16). Conclusions-More than one quarter of patients in a heterogeneous clinic population had treatment failure over a 2-year period. Prior ART adherence and other EHR data readily identify patient characteristics that could trigger specific interventions to improve ART outcomes. Keywords adherence; antiretroviral therapy; electronic health record; HIV; treatment failure; virologic failure With the use of combination antiretroviral therapy (ART), HIV mortality has declined dramatically in the United States. 1 However, treatment outcomes in the clinic setting continue to be substantially worse than those in clinical trials. 2 Treatment failure, whether attributable
EClinicalMedicine, 2020
Background: This prospective pilot study explored same-day point-of-care viral load testing in a setting in Ghana that has yet to implement virological monitoring of antiretroviral therapy (ART). Methods: Consecutive patients accessing outpatient care while on ART underwent HIV-1 RNA quantification by Xpert. Those with viraemia at the first measurement (T0) received immediate adherence counselling and were reassessed 8 weeks later (T1). Predictors of virological status were determined by logistic regression analysis. Drug resistance-associated mutations (RAMs) were detected by Sanger sequencing. Findings: At T0, participants had received treatment for a median of 8¢9 years; 297/333 (89¢2%) were on NNRTI-based ART. The viral load was 40 copies/mL in 164/333 (49¢2%) patients and 1000 copies/mL in 71/ 333 (21¢3%). In the latter group, 50/65 (76¢9%) and 55/65 (84¢6%) harboured NRTI and NNRTI RAMs, respectively, and 27/65 (41¢5%) had 1 tenofovir RAM. Among 150/164 (91¢5%) viraemic patients that reattended at T1, 32/150 (21¢3%) showed resuppression <40 copies/mL, comprising 1/65 (1¢5%) subjects with T0 viral load 1000 copies/mL and 31/85 (36¢5%) subjects with lower levels. A T0 viral load 1000 copies/mL and detection of RAMs predicted ongoing T1 viraemia independently of self-reported adherence levels. Among participants with T0 viral load 1000 copies/mL, 23/65 (35¢4%) showed resuppression <1000 copies/mL; the response was more likely among those with higher adherence levels and no RAMs. Interpretation: Same-day point-of-care viral load testing was feasible and revealed poor virological control and suboptimal resuppression rates despite adherence counselling. Controlled studies should determine optimal triaging modalities for same-day versus deferred viral load testing.
The Journal of Infection in Developing Countries, 2013
Introduction: Recently, there has been increasing interest in the role of “treatment as prevention” (TasP). Some of the questions regarding TasP strategies arise from the perceived difficulties in achieving and maintaining viral load (VL) suppression over time and the risk of emergence of viral resistance that could compromise future treatment options. This study was conducted to assess these questions in a resource-limited setting. Methodology: We performed a retrospective observational study of HIV-infected patients diagnosed in the pre-HAART era on follow-up at a private center from Buenos Aires, Argentina. Socio-demographic, clinical, and laboratory data were extracted from clinical charts. Analyses were performed to test for potential associations of selected variables with current virologic failure or use of third-line drugs. Results: Of 619 patients on follow-up, 82 (13.2%) were diagnosed in the pre-HAART era. At the time of our study, 79 (96.3%) patients were on HAART, with ...
PLoS ONE, 2014
In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM) versus routine laboratory (CD4/ haematology/biochemistry) and clinical monitoring (LCM) in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317) participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717), abacavir (n = 300), or nevirapine (n = 300). Of 1896 (81.8%) participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation), 1507 (79.5%) were on first-line and 389 (20.5%) on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (,50 cells/mm 3). Among 1207 (80.1%) first-line participants with viral load measured, HIV RNA was ,400 copies/ml in 963 (79.8%), 400-999 copies/ml in 37 (3.1%), 1,000-9,999 copies/ml in 110 (9.1%), and $10,000 copies/ml in 97 (8.0%). The proportion with HIV RNA ,400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5%) in CDM (76.3%) than in LCM (83.4%). Among 252 (64.8%) second-line participants with viral load measured (median 2.3 years after switch), HIV RNA was ,400 copies/ml in 226 (89.7%), with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.
Antiviral Therapy, 2012
Background: Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. Methods: Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA>1,000 copies/ml following suppression (<500 copies/ml), or >500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting >1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4 + T-cell count, HIV RNA and calendar period at treatment initiation. Results: Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). Conclusions: Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups. Achieving undetectable plasma HIV RNA is the goal of combination antiretroviral therapy (cART) [1-3] and is known to reduce the risk of clinical progression and mortality [4,5]. Maintaining this state is an indication of drug activity, but is challenging given that cART requires lifelong adherence. In reality, drug-related toxicities necessitate regimen changes and treatment interruptions occur or are unavoidable, for example, through drug stockouts in resource-limited settings [6-9]. Furthermore, therapeutic failure is observed if patients have