Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria.
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ABSTRACT:
SUBMITTER: Fajnzylber J
PROVIDER: S-EPMC8490281 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria.
Fajnzylber Jesse J Sharaf Radwa R Hutchinson John N JN Aga Evgenia E Bosch Ronald J RJ Hartogensis Wendy W Jacobson Jeffrey M JM Connick Elizabeth E Volberding Paul P Skiest Daniel J DJ Margolis David D Sneller Michael C MC Little Susan J SJ Gulick Roy M RM Mellors John W JW Gandhi Rajesh T RT Schooley Robert T RT Henry Keith K Tebas Pablo P Deeks Steve S Chun Tae-Wook TW Collier Ann C AC Hecht Frederick M FM Li Jonathan Z JZ
AIDS (London, England) 20211101 13
Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC. ...[more]
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Project description:BACKGROUND: Although considered an essential tool for monitoring the effect of combination antiretroviral treatment (CART), HIV-1 RNA (viral load, VL) testing is greatly influenced by cost and availability of resources. OBJECTIVES: To examine whether HIV infected patients who were initially successfully treated with CART have less frequent monitoring of VL over time and whether CART failure and other HIV-disease and sociodemographic characteristics are associated with less frequent VL testing. METHODS: The study included patients who started CART in the period 1999-2004, were older than 18 years, CART naive, had two consecutive viral load measurements of <400 copies/ml after 5 months of treatment and had continuous CART during the first 15 months. The time between two consecutive visits (days) was the outcome and associated factors were assessed using linear mixed models. RESULTS: We analyzed a total of 128 patients with 1683 visits through December 2009. CART failure was observed in 31 (24%) patients. When adjusted for the follow-up time, the mean interval between two consecutive VL tests taken in patients before CART failure (155.2 days) was almost identical to the interval taken in patients who did not fail CART (155.3 days). On multivariable analysis, we found that the adjusted estimated time between visits was 150.9 days before 2003 and 177.6 in 2008/2009. A longer time between visits was observed in seafarers compared to non-seafarers; the mean difference was 30.7 days (95% CI, 14.0 to 47.4; p<0.001); and in individuals who lived more than 160 kilometers from the HIV treatment center (mean difference, 16 days, p = 0.010). CONCLUSIONS: Less frequent monitoring of VL became common in recent years and was not associated with failure. We identified seafarers as a population with special needs for CART monitoring and delivery.
| S-EPMC2991345 | biostudies-other
Project description:BackgroundAs many as 40% of the 1 million children living with HIV (CLHIV) receiving antiretroviral treatment (ART) in resource limited settings have not achieved viral suppression (VS). Kenya has a large burden of pediatric HIV with nearly 140,000 CLHIV. Feasible, scalable, and cost-effective approaches to ensure VS in CLHIV are urgently needed. The goal of this study is to determine the feasibility and impact of point-of-care (POC) viral load (VL) and targeted drug resistance mutation (DRM) testing to improve VS in children on ART in Kenya.MethodsWe are conducting a randomized controlled study to evaluate the use of POC VL and targeted DRM testing among 704 children aged 1-14 years on ART at health facilities in western Kenya. Children are randomized 1:1 to intervention (higher frequency POC VL and targeted DRM testing) vs. control (standard-of-care) arms and followed for 12 months. Our primary outcome is VS (VL < 1000 copies/mL) 12 months after enrollment by study arm. Secondary outcomes include time to VS and the impact of targeted DRM testing on VS. In addition, key informant interviews with patients and providers will generate an understanding of how the POC VL intervention functions. Finally, we will model the cost-effectiveness of POC VL combined with targeted DRM testing.DiscussionThis study will provide critical information on the impact of POC VL and DRM testing on VS among CLHIV on ART in a resource-limited setting and directly address the need to find approaches that maximize VS among children on ART.Trials registrationNCT03820323.
| S-EPMC7644580 | biostudies-literature
Project description:ObjectivesIn low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.DesignMathematical model.MethodsWe developed a stochastic mathematical model representing the course of individual viral load, immunological response and survival in a cohort of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in southern Africa. We calculated cohort viral load (CVL; sum of individual viral loads) and used a mathematical relationship between individual viral load values and transmission probability to estimate the number of new HIV infections. Our model was parameterized with data from the International epidemiologic Databases to Evaluate AIDS Southern African collaboration. Sensitivity analyses were performed to assess the validity of the results in a universal 'test and treat' scenario, wherein patients start ART earlier after HIV infection.ResultsIf CD4 cell count alone was regularly monitored, the CVL was 2.6 × 10 copies/ml and the treated patients transmitted on average 6.3 infections each year. With routine viral load monitoring, both CVL and transmissions were reduced by 31% to 1.7 × 10 copies/ml and 4.3 transmissions, respectively. The relative reduction of 31% between monitoring strategies remained similar for different scenarios.ConclusionAlthough routine viral load monitoring enhances the preventive effect of ART, the provision of ART to everyone in need should remain the highest priority.
| S-EPMC3750130 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To estimate the diagnostic accuracy of point‐of‐care tests to detect high viral load levels in HIV‐positive people on ART.
| S-EPMC6517249 | biostudies-literature
Project description:The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of 'placebo' controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis. In total, 24 eligible prospective studies with 382 individuals with ≥5 plasma HIV RNA viral loads (pVLs) within the first 84 days post-ATI were included. Early-ART was defined as ART initiation within 6 months of HIV acquisition; others were classified as late-ART or unknown. Median age was 42 years, 91% male, 75% white, 45% received early-ART. Median time to pVL >50, >400, and >10,000 copies/mL was 16 days (interquartile range [IQR]:13-25), 21 (IQR:15-28), and 32 (IQR:20-35), respectively. PTC defined as pVL <50 copies/mL at day 84 occurred in 4% (n = 14) of participants (6% early-ART and 1% late-ART). Sustained PTC of pVL <50 copies/ml after 84 days is rare in PWH, especially in those starting ART late. Our findings inform future interventional HIV cure/remission trials on study size and design.
| S-EPMC11751076 | biostudies-literature
Project description:OBJECTIVES:WHO recommends HIV viral load (VL) testing 6 months after antiretroviral therapy (ART) initiation and every 12 months thereafter, but cost prohibits routine, universal VL testing in many developing countries. We sought to devise a targeted approach to routine VL monitoring that could reduce cost and identify those at low risk for virologic failure (VF). METHODS:We analysed screening data from a clinical trial enrolling adults on ART in Malawi. We identified risk factors associated with VF and employed the Knill-Jones method to assign summary score identifying persons at lower risk for VF. RESULTS:Among 957 adults, prevalence of VF was 9.4%. Factors independently associated with VF included age <38 years (OR 3.44, 95% CI 2.01-5.89), ART duration >2.5 years (OR 2.98, 95% CI 1.79-4.96), ART adherence <95% (OR 1.76, 95% CI 1.06-2.94), CD4 count <200 cells/μl (OR 5.94, 95% CI 3.27-10.78), haemoglobin <13 g/dl (OR 2.76, 95% CI 1.70-4.50) and CD8 count >885 cells/μl (OR 2.10, 95% CI 1.28-3.44). Our VF prediction summary score included all factors above except CD8 count and was fairly accurate with validated area under receiver operating characteristic curve of 0.76. Implementation could reduce VL testing by 65%. CONCLUSION:A simple score incorporating age, ART duration and adherence, and CD4 count can accurately identify adults at low risk for VF in a sub-Saharan African setting. In areas with high ART utilisation and limited VL testing capacity, a targeted approach could optimise routine VL monitoring while identifying adults in need of alternate ART regimens.
| S-EPMC5932246 | biostudies-literature
Project description:IntroductionHIV surveillance programs do not typically collect comprehensive data on antiretroviral therapy (ART). We validated a population-based measure of ART initiation that uses HIV viral load (VL) results in the absence of data on ART.MethodsWe used CD4/VL data reported to NYC HIV Surveillance for persons aged ≥13 years and diagnosed with HIV from 2006 to 2012 to validate estimates of ART initiation date based on 3 ART initiation definitions: (1) ≥1-log decline in copies per milliliter between 2 VLs over 3 months; (2) ≥2-log decline in copies per milliliter between 2 VLs over 3 months; and (3) the earliest of either a ≥1-log decline in VL over 3 months, or a change from detectable VL to undetectable VL (<400 copies/mL) over any interval. We plotted median CD4 counts by quarter before and after ART initiation to compare estimated initiation date with nadir of the CD4 trajectory.ResultsA total of 24,348 persons were diagnosed with HIV in NYC from 2006 to 2012. In all, 12,123 persons had probable ART initiation based on ≥2-log decline, 12,719 based on ≥1-log decline, and 14,311 based on ≥1-log decline or detectable-undetectable change. Lowest median CD4 count occurred at the estimated ART initiation date for all 3 definitions. The definition based on a ≥1-log VL decline or a change from detectable to undetectable VL captured more ART initiations and identified earlier initiation dates.ConclusionsSerial VL measures are a valid source for estimating ART initiation. A definition that includes a ≥1-log VL decline or a change from detectable to undetectable VL performed best.
| S-EPMC5584788 | biostudies-literature
Project description:Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.
| S-EPMC4934908 | biostudies-literature
Project description:BackgroundHaving 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is 1 of the 90:90:90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first 3 years after ART initiation.MethodsPatients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (<1000 copies/mL) were estimated using (1) strict intention to treat (ITT)-loss to follow-up (LTFU) and dead patients counted as having detectable VL; and (2) modified ITT-LTFU and dead patients were excluded. Logistic regression was used to identify predictors of viral suppression at 1 year after ART initiation using modified ITT.ResultsA total of 35,561 adults from 38 sites/16 countries and 2601 children from 18 sites/6 countries were included. When comparing strict with modified ITT methods, the proportion achieving VL suppression at 3 years from ART initiation changed from 45.1% to 90.2% in adults, and 60.6% to 80.4% in children. In adults, older age, higher CD4 count pre-ART, and homosexual/bisexual HIV exposure were associated with VL suppression. In children, older age and higher CD4 percentage pre-ART showed significant associations with VL suppression.ConclusionsLarge increases in the proportion of VL suppression in adults were observed when we excluded those who were LTFU or had died. The increases were less pronounced in children. Greater emphasis should be made to minimize LTFU and maximize patient retention in HIV-infected patients of all age groups.
| S-EPMC5634924 | biostudies-literature
Project description:BackgroundHIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.MethodsWe analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.FindingsBetween Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022 men who have sex with men and 14,481 people who inject drugs. Median incidence of HIV was 0·87% (IQR 0·40-1·17) in men who have sex with men and 1·43% (0·60-4·00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0·81, 95% CI 0·62-0·91; p<0·0001) than all other measures, although correlation was significant with aware viral load (0·59, 0·27-0·79; p=0·001), population viral load (0·51, 0·16-0·74; p=0·007), and population ART coverage (-0·54, -0·76 to -0·20; p=0·004). In-care viral load was not correlated with HIV incidence (0·29, -0·10 to 0·60; p=0·14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4·34%, and ART use in HIV-positive individuals would need to increase by 19·5%.InterpretationPrevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.FundingUS National Institutes of Health, Elton John AIDS Foundation.
| S-EPMC4863069 | biostudies-literature