Follow-up Viral Load Research Articles

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

Impact of enhanced adherence counselling on viral re-suppression among adolescents and young persons with persistent viremia.

Kenya ART guidelines recommend three sessions of enhanced adherence counselling (EAC) following detectable viral load. The objective of this study was to assess completion of EAC sessions and factors associated with viral re-suppression amongst adolescents and young persons (AYPs) with persistent viremia in Western Kenya. A retrospective analysis of routinely collected data abstracted from viral load registers was done. AYP with persistent viremia (consecutive viral load ≥1000 copies/ml) between October 2017 to September 2019 were followed for 12 months; those with more than one follow-up viral load results were analyzed. EAC was satisfactory if at least three sessions attended, barriers identified and addressed. Morisky scores 0 and at least 1 indicated optimal and sub-optimal adherence, respectively. Logistic regression models were used to assess predictors of viral load suppression (VLS). Of 124 AYPs with persistent viremia, 118 (95.2%) had documented follow-up viral load results and 119 (96%) completed three EAC sessions. Overall, 55 (47%) clients re-suppressed during the study period. AYPs who had satisfactory EAC sessions had higher odds of achieving VLS [odds ratio (OR) = 3.7, 95% confidence interval (CI): 1.6-8.1]. Similarly, AYPs with an optimal adherence had eight times (OR = 8.1, 95% CI: 3.5-18.5) higher odds of achieving VLS, and those who were suppressed at 6 months post-ART initiation had higher odds of achieving VLS at 12-months (OR = 2.5, 95% CI: 1.1-5.8). Satisfactory EAC sessions and optimal ART adherence was strongly associated with viral re-suppression among AYPs with persistent viremia. Continued support to EAC intervention is critical to improve treatment outcome among AYP living with HIV.

Longitudinal viral load outcomes of adults with HIV after detectable viremia on tenofovir, lamivudine, and dolutegravir.

To inform optimal management of HIV viremia on tenofovir, lamivudine, and dolutegravir (TLD), we examined viral load (VL) outcomes of a large cohort of adult PWH on TLD in Nigeria. We conducted a retrospective study of adult PWH who had ≥1 VL after initiating TLD during January 2017-February 2023. VLs were categorized as undetectable (≤50 copies/ml), low low-level viremia (LLV, 51-199 copies/ml), high LLV (200-999 copies/ml), virologic nonsuppression (VLNS, ≥1000 copies/ml), and virologic failure (VF, ≥2 consecutive VLNS results). Among patients with ≥2 VLs on TLD, we described how viremia changed over time and examined virologic outcomes after VF. We identified predictors of subsequent VLNS using mixed-effects logistic regression and conducted planned contrasts between levels of VL result and regimen types. Analysis of 82,984 VL pairs from 47,531 patients demonstrated viral resuppression to ≤50 copies/ml at follow-up VL in 66.7% of those with initial low LLV, 59.1% of those with initial high LLV, and 48.9% of those with initial VLNS. Of 662 patients with a follow-up VL after VF, 94.6% stayed on TLD; of which 57.8% (359/621) were undetectable at next VL without regimen change. Previous low LLV [adjusted odds ratio (aOR) 1.74, 1.56-1.93], high LLV (aOR 2.35, 2.08-2.65), and VLNS (aOR 6.45, 5.81-7.16) were associated with increasingly higher odds of subsequent VLNS, whereas a previously undetectable VL (aOR 1.08, 0.99-1.71) on TLD was not. Despite increased odds of subsequent VLNS, most PWH with detectable viremia on TLD, including those with VF, will resuppress to an undetectable VL without a regimen change.

Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.

Virological, weight, and drug resistance outcomes among patients initiating a dolutegravir-based first-line antiretroviral therapy regimen in Zimbabwe.

Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up in Africa. However, clinical experience with DTG and patterns of HIV drug resistance (HIVDR) are sparse in Zimbabwe. We assessed virological, weight, and HIVDR outcomes among individuals initiating on a DTG-based ART. We conducted a prospective cohort study among HIV-infected adult (≥18 years old) individuals attending care at Parirenyatwa hospital, Harare, Zimbabwe between October 2021 and April 2023. Viral load and weight were assessed at both baseline and follow-up (≥24weeks) visits. HIVDR genotyping was performed by Sanger sequencing among participants with virological failure (viral load ≥1000 copies/ml) at follow-up visit. Factors associated with weight gain were determined using logistic regression analysis on STATA 17.0. One hundred and seventy-two participants were enrolled in the study. The median [interquartile range (IQR) age was 39 (29-48)] years whilst the median (IQR) CD4 + cell count and log 10 viral load at enrolment was 175 (58-328) cells/μl and 5.41 (4.80-5.74), respectively. After a median (IQR) duration of 27 (25-30) weeks on DTG, of the 131 participants with follow-up viral load data available, 129 (98%) had viral load less than 1000 copies/ml and among the 2 (2%) participants with viral load at least 1000 copies/ml, no emergent HIVDR was detected. We observed a significant increase in weight among the participants. The average weight gain was 5.25 kgs ( P < 0.0001). Baseline CD4 + cell count at least 200 cells/μl was significantly associated with at a smaller weight gain [odds ratio (OR) = 0.26; 95% confidence interval (CI) 0.12-0.58, P = 0.001]. We found high virological suppression and an increased weight among people initiating on DTG in a resource-limited setting. Encouragingly, HIVDR to DTG remains rare.

Clinical outcomes after extended 12-month antiretroviral therapy prescriptions in a community-based differentiated HIV service delivery programme in South Africa: a retrospective cohort study.

There is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) versus standard 6-month prescriptions and consultations (6M scripts) and clinical outcomes. We performed a retrospective cohort study using routine, de-identified data from 59 public clinics in KwaZulu-Natal, South Africa. We included PLHIV aged ≥18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12-month retention-in-care (≤90 days late for all visits) and viral suppression (<50 copies/ml) between prescription groups. Among 27,148 PLHIV referred for community ART during Jun-Dec 2020, 57.4% received 12M scripts. The median age was 39 years and 69.4% were women. Age, sex, prior community ART use and time on ART were similar across groups. However, more of the 12M script group had dolutegravir-based regimens (60.0% vs. 46.3%). The median (interquartile range) number of clinic visits in the year of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention was 94.6% (95% confidence interval [CI]: 94.2%-94.9%) among those receiving 12M scripts and 91.8% (95% CI: 91.3%-92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 92.4% (95% CI: 92.0%-92.9%) in the 12M group and 91.4% (95% CI: 90.8%-92.0%) in the 6M group were suppressed. After adjusting for age, sex, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI: 1.01-1.05) and suppression (aRR: 1.00, 95% CI: 0.99-1.01) were similar across groups. Among PLHIV referred for community ART with a recent suppressed VL, the use of 12M scripts reduced clinic visits without impacting short-term clinical outcomes. 12M scripts should be considered for differentiated service delivery programmes.

Point-of-care viral load testing to manage HIV viraemia during the rollout of dolutegravir-based ART in South Africa: a randomised feasibility study (POwER).

Data is required regarding the feasibility of conducting a randomised trial of point-of-care viral load (VL) testing to guide management of HIV viraemia, and to provide estimates of effect to guide potential future trial design. Two public South African clinics during the dolutegravir-based antiretroviral therapy (ART) rollout. We randomised adults receiving first-line ART, with recent VL ≥1000 copies/mL, in a 1:1 ratio to receive point-of-care Xpert HIV-1 VL versus standard-of-care laboratory VL testing, after 12 weeks. Feasibility outcomes included proportions of eligible patients enrolled and completing follow-up, and VL process outcomes. Estimates of effect were assessed using the trial primary outcome of VL <50 copies/mL after 24 weeks. From August 2020-March 2022 we enrolled 80 eligible participants, an estimated 24% of those eligible. 47/80 (58.8%) were women, and median age was 38.5 years (IQR 33-45). 44/80 (55.0%) were receiving dolutegravir and 36/80 (465.0%) were receiving efavirenz. After 12 weeks, point-of-care participants received VL results after median 3.1 hours (IQR 2.6-3.8), versus 7 days (IQR 6-8, p<0.001) in standard-of-care. 12-week follow-up VL was ≥1000 copies/mL in 13/39 (33.3%) point-of-care participants and in 16/41 (39.0%) standard-of-care participants; 11/13 (84.6%) and 12/16 (75.0%) switched to second-line ART respectively. After 24 weeks, 76/80 (95.0%) completed follow-up. 27/39 (69.2% [95%CI 53.4-81.4]) point-of-care participants achieved VL <50 copies/ml versus 29/40 (72.5% [57.0-83.9]) standard-of-care participants. Point-of-care participants had median 3 (IQR 3-4) clinic visits versus 4 (IQR 4-5) in standard-of-care (p<0.001). It was feasible to conduct a trial of point-of-care VL testing to manage viraemia. Point-of-care VL lead to quicker results and fewer clinical visits, but estimates of 24-week VL suppression were similar between arms.

Risk of Sexual Transmission of HIV with Antiretroviral Therapy and Variable or Suppressed Viral Load

&#x0D; The absolute risk of HIV transmission through sexual activity, reported as incidence rates of observed seroconversions across person-years of follow-up, ranged widely across the included studies of sex partners living with HIV with variable (or unreported) viral loads.&#x0D; Two studies included sex partners living with HIV with suppressed viral loads of fewer than 200 copies/mL, reporting no phylogenetically linked seroconversions in either study.&#x0D; Most studies in this report included data from heterosexual serodiscordant sex partners and did not report follow-up viral loads of sex partners living with HIV.&#x0D; The included studies incorporated variable methods, investigated a broad variety of populations and exposures, and demonstrated a wide range of methodological strengths and limitations.&#x0D;

Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana.

Individuals living with human immunodeficiency virus (HIV) who experience virological failure (VF) after combination antiretroviral therapy (cART) initiation may have had low-frequency drug resistance mutations (DRMs) at cART initiation. There are no data on low-frequency DRMs among cART-naïve HIV-positive individuals in Botswana. We evaluated the prevalence of low-frequency DRMs among cART-naïve individuals previously sequenced using Sanger sequencing. The generated pol amplicons were sequenced by next-generation sequencing. We observed low-frequency DRMs (detected at <20% in 33/103 (32%) of the successfully sequenced individuals, of whom four also had mutations detected at >20%. K65R was the most common low-frequency DRM detected in 8 individuals. Eighty-two of the 103 individuals had follow-up viral load data while on cART. Twenty-seven of the 82 individuals harbored low-frequency DRMs. Only 12 of 82 individuals experienced VF. The following low-frequency DRMs were observed in four individuals experiencing VF: K65R, K103N, V108I, and Y188C. No statistically significant difference was observed in the prevalence of low-frequency DRMs between individuals experiencing VF (4/12) and those not experiencing VF (23/70) (P = .97). However, individuals with non-nucleoside reverse transcriptase inhibitors-associated low-frequency DRMs were 2.68 times more likely to experience VF (odds ratio, 2.68; 95% confidential interval, 0.4-13.9) compared with those without (P = .22). Next-generation sequencing was able to detect low-frequency DRMs in this cohort in Botswana, but these DRMs did not contribute significantly to VF.

Viral load monitoring for people living with HIV in the era of test and treat: progress made and challenges ahead – a systematic review

BackgroundIn 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs.MethodsA literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure).ResultsThe search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12–93% median: 74% IQR: 46–82%) and study populations (adults (range: 25–96%, median: 67% IQR: 50–84%), children, adolescents/young people (range: 2–94%, median: 72% IQR: 47–85%), and pregnant women (range: 32–82%, median: 57% IQR: 43–71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed.ConclusionsSubstantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the “failure cascade” in PLHIV on ART who fail to achieve viral suppression.

COVID-19 impact on testing, diagnosis and care of people with sexually transmitted infections in a low human development region, Minas Gerais, Brazil

This study aimed to analyze the impact of the COVID-19 pandemic on the care of people with Sexually Transmitted Infections (STIs) in a region of low human development, located in Minas Gerais, Brazil. Methods: The number of monthly procedures during pandemic period, January to December 2020, and comparison period, January to December 2019, in a SUS regional clinic, a reference for STIs, were analyzed. Visits were categorized into follow-up appointments, rapid tests, viral loads and first appointment due a recent diagnosis. Comparison between both periods was performed by frequency analysis, difference in the mean monthly attendances (DM) and prevalence ratios (PR), considering ratio between the proportion of attendances in the pandemic period/proportion of attendances in the comparative period. During the pandemic period, the average number of monthly consultations reduced for all consultations (DM = -105.25) and categories. Proportion of consultations reduced for rapid tests (PR = 0.46; 95% CI = 0.41-0.52) and first consultation due recent diagnosis (PR = 0.90; 95% CI = 0.65-1, 25), procedures that are usually scheduled by the user. There was an increase in the proportion of follow-up visits (PR = 1.18; 95% CI = 1.09-1.27) and viral load tests (PR = 1.41; 95% CI = 1.32-1, 88), monitoring procedures usually scheduled by the clinic. There was a trend to maintain risk exposure for STIs. Conclusion: These findings may guide better strategies to care for individuals with STIs.

886. The Impact of the COVID-19 Pandemic on Clinical Follow-Up, Monitoring and Regimen Discontinuation for People Living with HIV in the US

BackgroundThe COVID-19 pandemic has disrupted health care services for people living with HIV (PLWH). This study aimed to compare rates of clinical visits, viral load monitoring and antiretroviral therapy (ART) regimen discontinuation among virally suppressed PLWH in the US before and during the COVID pandemic.MethodsThe study population consisted of ART-experienced PLWH ≥18 years of age and active in care in the OPERA cohort within 2 years prior to 31OCT2020. Virally suppressed PLWH (i.e., viral load < 200 copies/mL) were included if they switched to either dolutegravir/lamivudine or a dolutegravir- or bictegravir-based 3-drug regimen between 01MAY2019 and 30APR2020. The study periods spanned from 01MAY2019 to 28FEB2020 (pre-COVID) and 01MAR2020 to 31OCT2020 (during COVID). Incidence rates of clinical visits, viral load measurements and regimen discontinuation were estimated using univariate Poisson regression for both study periods. In-person visits comprised any scheduled or walk-in outpatient, inpatient, emergency or laboratory visit. Telehealth visits comprised any phone or video encounters.ResultsThe study included 4806 PLWH in the pre-COVID and 4992 in the COVID period. Rates of in-person visits were reduced almost 2-fold during COVID, while telehealth visits increased almost 9-fold, resulting in an overall reduction in any visits rates from 10.07 visits per person-year (95% CI: 9.93, 10.21) pre-COVID to 7.10 (95% CI: 7.01, 7.19) during COVID [Fig 1]. Rates of viral load measurements dropped from 2.99 viral loads per person-year (95% CI: 2.92, 3.07) pre-COVID to 1.97 (95% CI: 1.92, 2.02) during COVID [Fig 2]. Regimen discontinuation rates were also reduced from 14.3 discontinuations per 100 person-years pre-COVID (95% CI: 12.7, 16.1) to 9.6 (95% CI: 8.6, 10.8) during COVID [Fig 3]. In both study periods, virologic failures were detected in < 1% of PLWH with ≥ 1 viral load.Figure 1. Incidence rates for overall, in-person, and telehealth visits during the pre-COVID (open circle) and the COVID (filled circle) study periods Incidence rates for viral load measurements during the pre-COVID (open circle) and the COVID (filled circle) study periods Incidence rates for regimen discontinuation during the pre-COVID (open circle) and the COVID (filled circle) study periods ConclusionThe COVID pandemic has led to an important reduction in the frequency and type of clinical follow-up visits and viral load monitoring among virally suppressed PLWH in the US. A reduction in regimen discontinuation rates was also observed, presumably associated to less frequent follow-up. The long-term impact of the pandemic on HIV care remains uncertain.Disclosures Gerald Pierone, MD, Epividian (Board Member) Jennifer S. Fusco, BS, Epividian, inc (Employee) Laurence Brunet, PhD, Epividian, inc (Employee) Cassidy Henegar, PhD, GSK (Shareholder)ViiV Healthcare (Employee) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Supriya Sarkar, PhD, GSK (Shareholder)ViiV Healthcare (Employee) Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee) Andrew Zolopa, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael B. Wohlfeiler, MD, Epividian, inc (Board Member)ViiV Healthcare (Research Grant or Support) Gregory Fusco, MD, MPH, Epividian, inc (Employee)

873. A Retrospective Cohort Study on Treatment Outcomes of Patients on Third-Line Therapy at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia

BackgroundIn Zambia, third-line regimens consist of a switch to darunavir/ritonavir (DRV/r) and/or raltegravir (RAL) and/or etravirine (ETV), and as of 2017, dolutegravir (DTG), from a failing second-line therapy.5 We assessed virologic suppression (HIV viral load (VL) ≤1000 copies/ml per Zambian national guidelines), immunological response, and patterns of HIV drug resistance mutation among patients on third-line ART at the University Teaching Hospital (UTH) in Lusaka, Zambia.MethodsA retrospective evaluation of adults ≥18 years old on third-line ART regimens at UTH between January 2012 to June 30, 2020 was conducted. Patients were referred for second-line virologic failure defined as HIV RNA VL > 1000 copies/mL on two consecutive measurements after 6 months on second-line ART.5 We assessed virologic suppression VL ≤1000 copies/ml, CD4, mutations, and third-line regimens of this cohort. Patients were excluded if they were on third-line ART < 6 months or received RAL and/or ETV and/or DTG before starting third-line ART. ResultsA total of 539 patients were included; 231 males (42.9%) and 308 (57.1%) females. The mean age of third-line initiation was 29.8 years; mean time from ART initiation to third-line initiation was 9.9 years. Out of 25 combination 349 (64.7%) received DTG, 272 (50.5%) DRV/r, 85(15.8%) ETR, and 49 (9.1%) RAL. There were 215 (39.9%) genotypes; common mutations were to zidovudine (80%), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (78%), and protease inhibitors (PIs) (41%). Patients with at least one viral load and CD4 upon third-line initiation was 296 (54.9%) and 350 (64.9%), respectively. Among patients with sufficient data (21%, n=115), VL suppression increased from 44 (38%) patients at baseline to 53 (46%) at next available follow-up; with mean baseline VL and follow-up VL of log10 3.60 and 3.33, respectively. The immunologic response revealed 49 (56.3%) had CD4 increase with mean increase of 61.1 cells/mm3. (See Table 1.) ConclusionWe found moderate improvements in VL suppression and immunologic response. Nearly all third-line patients had genotypic resistance to first-line NNRTI and nearly half to second-line PI regimens. Quality improvement measures are needed to improve viral load timing following ART changes to better assess regimen efficacy.Disclosures All Authors: No reported disclosures

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal

BackgroundSecond-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal.MethodsHIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges.ResultsWe enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding.ConclusionsThe RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges.Trial registrationClinicalTrials.govNCT03394196. Registered on January 9, 2018.

The Suboptimal Pediatric HIV Viral Load Cascade: Multidistrict Cohort Study Among Children Taking Antiretroviral Therapy in Lesotho, Southern Africa.

Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

Universal Screening for Hepatitis C Virus in the ED Using a Best Practice Advisory.

IntroductionIn 2019 the United States Preventive Services Task Force (USPSTF) released draft guidelines recommending universal hepatitis C virus (HCV) screening for individuals aged 18–79. We aimed to assess the efficacy of an emergency department-based HCV screening program, by comparing screening practices before and after its implementation.MethodsWe performed a retrospective cohort analysis of two temporally matched, 11-month study periods, corresponding to before and after the implementation of a best practice advisory (BPA). Patients were screened for anti-HCV antibody (Ab), and positive results were followed by HCV viral load (VL) testing. The primary implementation outcome was ED testing volume (number of tests performed/month). The primary screening outcomes were the seroprevalence of anti-HCV Ab and HCV VL. We describe data with simple descriptive statistics.ResultsThe median age of patients was similar between periods (pre: 50 years [interquartile range [IQR] 34–62], post: 47 years [IQR 33–59]). Patients screened were more likely to be males in the pre-BPA period (Male, pre: 60%, post: 49%). During the pre-BPA study period, a total of 69,604 patients were seen in the ED, and 218 unique patients were screened for HCV (mean 19.8 tests/month). During the post-BPA study period, a total of 68,225 patients were seen in the ED, and 14,981 unique patients were screened for HCV (mean 1361.9 tests/month). Anti-HCV Ab seroprevalence was 23% (51/218) and 9% (1340/14,981) in the pre-BPA and post-BPA periods, respectively. In the pre-BPA period, six patients with a positive anti-HCV Ab level had follow-up VL testing (detectable in three). In the post-BPA period, reflex VL testing was performed in most patients (91%, 1225/1,340), and there were 563 patients with detectable VLs, indicating active infection.ConclusionOur study shows that using a universal BPA-driven screening protocol can dramatically increase the number of patients screened for HCV and increase the number of new HCV diagnoses.

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

BackgroundProgress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar.MethodsWe conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure.ResultsWe included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates.ConclusionsVL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

Emergence of Human Immunodeficiency Virus-1 Drug Resistance During the 3-Month World Health Organization-Recommended Enhanced Adherence Counseling Period in the CART-1 Cohort Study.

BackgroundIn resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (≥80 c/mL) after EAC.MethodsWe included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL ≥80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant’s antiretroviral therapy (ART) regimen (range, 0–3; 3 indicates complete susceptibility).ResultsAmong 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL ≥1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL ≥80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25–) to 0.25 (IQR = 0.25–1) during the EAC period (P = .16).ConclusionsDespite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC.

Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania

BackgroundGlobally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART).MethodsGIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up.DiscussionThis randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART.Trial registrationThis trial is registered with ClinicalTrials.gov (NCT04233242; registered 18.01.2020). More information: www.givemove.org.

Modelling drugs interaction in treatment-experienced patients on antiretroviral therapy

Understanding pharmacology and drug resistance patterns plus appropriate use of laboratory testing is vital for managing treatment-experienced patients with new agents. While we acknowledge that patients with extensive drug resistance now have multiple options for suppressive therapy, and expert care is essential to avoid the rapid emergence of resistance to these new agents, clinicians are unaware of the inherent (hidden) patterns created by combined drug regimens that could trigger adverse drug reactions. This paper proposes a novel hybrid system framework that combines soft computing techniques, for drugs interaction modelling and precise patient response optimisation. A Fuzzy Logic system was developed to address the uncertainty in treatment change episodes (TCEs). A weighted least-squares cost function was then employed to auto-tune hyperparameters for training the neural network. After acceptable tuning, the final hyperparameters served the neural network—to efficiently learn the ensuing patterns for precice drug interaction classification. The proposed framework was experimented with clinical data of TCEs from two disparate sources: a publicly available HIV database (the Stanford HIV database: https://hivdb.stanford.edu ), and clinical data collected from 13 health centers managing HIV cases in Akwa Ibom State of Nigeria (the Akwa-Ibom HIV database). In both databases, a correlation of prognostic markers suggests strong association between first line CD4 and follow-up CD4 counts; while a moderately weak association was observed for first line and follow-up viral loads. Correlation of physiological feature gave very strong association between first line and follow-up body mass index in Akwa-Ibom database. Analysis of the patients progress explains the decreased potency of CD4 count and body mass index as HIV predictors. The root mean square error (RMSE) and classification accuracy were used as performance metrics for measuring the precision of our hybrid framework. Results obtained showed improved RMSE and classification accuracy for both databases, when compared with existing works.