Sustained Virologic Suppression Research Articles

Ex vivo sensitivity to broadly neutralizing antibodies and anti-CD4 antibody UB-421 of infectious viral isolates from people living with multidrug-resistant HIV

People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking. We examined levels of immune activation and exhaustion markers on CD8+ T cells and the intact HIV proviral DNA burden in 11 PLWH with MDR viruses. For comparison purposes, we included a control group consisting of 27 ART-naïve viremic PLWH. In addition, we determined the sensitivity of infectious viral isolates obtained from the participants against eight bNAbs (3BNC117, 10-1074, VRC01, VRC07, N6, 10E8, PGDM1400, and PGT121) and two anti-CD4 antibodies (ibalizumab and UB-421) using a TZM-bl-based neutralization/suppression assay. The level of intact HIV proviral DNA was comparable between the two groups (P=0.29). The levels of activation and exhaustion markers PD-1 (P=0.0019), TIGIT (P=0.0222), 2B4 (P=0.0015), CD160 (P=0.0015), and CD38+/HLA-DR+ (P=0.0138) were significantly lower in the MDR group. The infectious viral isolates from each study participant with MDR HIV were resistant to at least 2 bNAbs; however, they were sensitive to at least one of the CD4-binding and non-CD4-binding site antibodies. The majority of participants had ibalizumab-sensitive viruses although the isolates from some participants showed reduced sensitivity to ibalizumab. Notably, none of the 93 viral isolates obtained from the participants were resistant to UB-421. Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Rapid Start of Antiretroviral Therapy in a Large Urban Clinic in the US South: Impact on HIV Care Continuum Outcomes and Medication Adherence.

Rapid start of antiretroviral therapy (ART) has been associated with improvement in several HIV-related outcomes in clinical trials as well as demonstration projects, but how regional and contextual differences may affect the effectiveness of this intervention necessitates further study. In this study of a large, urban, Southern US clinic-based retrospective cohort, we identified 544 patients with a new diagnosis of HIV during 2016 to 2019 and compared HIV care continuum outcomes for the first 12 months of care before and after rapid start implementation. Kaplan-Meier time-to-event curves were used to summarize time to virologic suppression, and stepwise Cox, linear, and logistic regression models were used to create multivariate models to evaluate the association between rapid start and time to virologic suppression, medication adherence, and retention in care and sustained virologic suppression, respectively. We found that rapid start was significantly associated with improved medication adherence scores (+15.37 points, 95% confidence interval [CI] 9.36-21.39, P < .01) and retention in care (adjusted odds ratio = 1.51, 95% CI 1.05-2.19, P = .03). Time to virologic suppression (median 2.46 months before, 2.56 months after rapid start) and sustained virologic suppression were not associated with rapid start in our setting. Though rapid start was associated with improved medication adherence and retention in care, more support may be needed to achieve the same outcomes seen in other studies and sustained over the entire HIV care continuum, especially in settings with significant patient and systemic barriers to care such as unstable housing, lack of Medicaid expansion, and frequent coverage interruptions.

The Determinants of Elevated Pathobiological Determination of Atherosclerosis in Youth Risk Score in Perinatally HIV-Infected Adolescents in South Africa.

Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease. We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non-high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY. Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9-17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8-14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09). A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health.

Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland

The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March2023. Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664ng/mL. Exploratory statistical analyses found 35% (p<0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. This work was funded by the Swiss National Science Foundation, grant number N◦ 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).

HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study

Infants born with HIV-1 require lifelong antiretroviral therapy (ART). We aimed to assess whether very early ART in neonates might restrict HIV-1 reservoirs, an important step towards ART-free remission. IMPAACT P1115 is an ongoing, phase 1/2, proof-of-concept study in which infants were enrolled at 30 research clinics in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the USA, Zambia, and Zimbabwe) into two cohorts. Infants at least 34 weeks' gestational age at high risk for in-utero HIV-1 with either untreated maternal HIV-1 (cohort 1) or who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (maternal ART permissible; cohort 2) were included. All infants initiated treatment within 48 h of life. Cohort 1 initiated three-drug nevirapine-based ART, and cohort 2 initiated three-drug nevirapine-based prophylaxis then three-drug nevirapine-based ART following HIV diagnosis by age 10 days. We added twice-daily coformulated oral ritonavir 75 mg/m2 and lopinavir 300 mg/m2 from 14 days of life and 42 weeks postmenstrual age. We discontinued nevirapine 12 weeks after two consecutive plasma HIV-1 RNA levels below limit of detection. We tracked virological suppression, safety outcomes, and meeting a predetermined biomarker profile at age 2 years (undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage) to assess qualification for analytical treatment interruption. This study is registered with ClinicalTrials.gov, NCT02140255. Between Jan 23, 2015, and Dec 14, 2017, 440 infants were included in cohort 1 and 20 were included in cohort 2. 54 of these infants (34 from cohort 1 and 20 from cohort 2) had confirmed in-utero HIV-1 and were enrolled to receive study ART. 33 (61%) of 54 infants were female and 21 (39%) were male. The estimated probability of maintaining undetectable plasma RNA through to 2 years was 33% (95% CI 17-49) in cohort 1 and 57% (28-78) in cohort 2. Among infants maintaining protocol-defined virological control criteria through to study week 108, seven of 11 (64%, 95% CI 31-89) in cohort 1 and five of seven (71%, 29-96) in cohort 2 had no detected HIV-1 DNA. Ten of 12 (83%, 52-100) in cohort 1 and all seven (100%, 59-100) in cohort 2 tested HIV-1 antibody-negative at week 108. Among 54 infants initiated on very early ART, ten (19%; six in cohort 1 and four in cohort 2) met all criteria for possible analytical treatment interruption. Reversible grade 3 or 4 adverse events occurred in 15 (44%) of 34 infants in cohort 1 and seven (35%) of 20 infants in cohort 2. Very early ART for in-utero HIV-1 can achieve sustained virological suppression in association with biomarkers indicating restricted HIV-1 reservoirs by age 2 years, which might enable potential ART-free remission. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks.

Human immunodeficiency virus type 1 (HIV-1) infection is treated with antiretroviral therapy (ART), usually consisting of 2-3 different drugs, referred to as combination ART (cART). Our recent randomized clinical trial comparing a switch to dolutegravir monotherapy with continuation of cART in early-treated individuals demonstrated sustained virological suppression over 48 weeks. Here, we characterize the longitudinal landscape of the HIV-1 reservoir in these participants, with particular attention to potential differences between treatment groups regarding evidence of evolution as a proxy for low-level replication. Near full-length HIV-1 proviral polymerase chain reaction and next-generation sequencing was applied to longitudinal peripheral blood mononuclear cell samples to assess proviral evolution and the potential emergence of drug resistance mutations (DRMs). Neither an increase in genetic distance nor diversity over time was detected in participants of both treatment groups. Single proviral analysis showed high proportions of defective proviruses and low DRM numbers. No evidence for evolution during dolutegravir monotherapy was found in these early-treated individuals.

Sustained viral suppression with dolutegravir monotherapy over 192 weeks in patients starting combination antiretroviral therapy during primary HIV infection (EARLY-SIMPLIFIED): a randomized, controlled, multi-site, non-inferiority trial.

Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a four-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144 and 192 weeks; noninferiority margin 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group vs 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13,308 and 4,897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. This trial suggests that early cART initiation during primary HIV-infection allows sustained virological suppression after switching to DTG monotherapy. NCT02551523.

Patient perspectives of antiretroviral pharmacy services: A cross-sectional cohort study.

Adherence to antiretroviral therapy (ART) remains the main predictor of sustained HIV virologic suppression for people with HIV (PWH). Mail-order pharmacy services are often offered to patients as an alternative option to traditional pharmacy services. Some payers mandate ART to be dispensed from specific mail-order pharmacies regardless of patient choice complicating ART adherence for patients affected by social disparities. Yet, little is known about patient perspectives regarding mail-order mandates. Eligible patients of the HIV program at University of Nebraska Medical Center with experience receiving ART from both a local and mail-order pharmacy were invited to complete a 20-question survey with three core sections: experiences/perspectives on local and mail-order pharmacy settings; pharmacy attributes rankings; and pharmacy preference. Paired t-tests and Mann-Whitney tests were used to compare the agreement scores of pharmacy attributes. Sixty patients (N = 146; 41.1%) responded to the survey. Mean age was 52 years. Most were male (93%) and White (83%). The majority of participants were on ART for HIV treatment (90%) and 60% were using mail-order pharmacies for their prescription services. Significant scoring differences (p<0.05) were observed for all pharmacy attributes favoring local pharmacies. Refilling ease was the most important attribute noted. More respondents (68%) preferred local pharmacies versus mail-order pharmacies. Payer associated mail-order pharmacy mandates were experienced by 78% with half believing the mandates impacted their medical care negatively. In this cohort study, respondents preferred local pharmacies compared to mail-order pharmacy for ART prescription services and noted ease of refilling as the most important pharmacy attribute. Two-thirds of respondents believed mail-order pharmacy mandates negatively affected their health. Insurance payers should consider the removal of mail-order pharmacy mandates to allow patient choice of pharmacy, which may help remove barriers to ART adherence and improve long-term health outcomes.

Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks.

We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study. Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m2, and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis). At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4+ cell count (<200 cells/mm3; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1-2); no serious drug-related AEs occurred. Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting.

HIV Infection Indicator Disease-Based Active Case Finding in a University Hospital: Results from the SHOT Project

In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as "the three 95": 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4+ cells/µL and 60% with less than 350 CD4+ cells/µL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count <100/mm3, one (9.1%) <200/mm3, and one (9.1%) <300/mm3. Regarding risk factors, 81.8% declared having had unprotected sexual intercourse and 54.5% were heterosexual. All patients promptly started a combination antiretroviral regimen and 10 (90.9%) obtained an undetectable HIV-RNA status. Eight of the eleven (72.7%) patients are currently on follow-up in our outpatient clinic. A proactive indicator disease-guided screening can help avoid missed opportunities to diagnose HIV infection in a hospital setting. Implementing this kind of intervention could favor early diagnosis and access to treatment.

Virological failure of antiretroviral therapy and associated social and clinical factors in children and adolescents living with HIV

According to the World Health Organization, sustained virological suppression of 90 % should be achieved among children and adolescents living with HIV / AIDS, which makes it important to assess the prevalence of virological failure of antiretroviral therapy. The aim of this study was to determine the prevalence of virological failure and the clinical factors associated with it, as well as therapeutic drug monitoring in groups divided by the viral load level among children and adolescents with HIV. Materials and Methods: A retrospective analysis of the medical records of 184 children and adolescents receiving antiretroviral therapy and registered at the Irkutsk Regional Center for the Prevention and Control of AIDS and Infectious Diseases, Irkutsk, was carried out. The study included 172 children aged 1-18 years with perinatal HIV infection. Patients were divided into groups depending on the level of viral load: group 1 – 21 patients with viral load &gt; 1000 copies/ml of plasma, group 2 – 42 patients with viral load 50– 1000 copies/ml of plasma, group 3 – 109 patients with undetectable viral load (&lt; 50 copies/ml). All patients underwent standard tests in accordance with clinical guidelines for the treatment of HIV infection in children, as well as therapeutic drug monitoring. Results. Against the background of ongoing antiretroviral therapy, a significant number of patients 21 / 172 (12,2 %) experienced virological failure. The proportion of children and adolescents with incomplete suppression of HIV replication is 42 / 172 (24,4 %). Statistically significant differences were obtained by changing the ART regimen (p = 0,031). In the first group, the proportion of patients who changed the therapy regimen is 7 / 21 (33,3 %), which is two times less than in the group with a zero viral load of 70 / 109 (64,2 %). There are differences in the proportion of children and adolescents with zero concentrations of ritonavir and lopinavir (p = 0,020 and p = 0,012) in the three compared groups. The distribution of patients with zero concentrations was as follows: for ritonavir in the first group 3 / 17 (17,6 %), in the second – 8/37 (21,6 %), in the third group – 4/80 (5 %); for lopinavir – 4/17 (23,5 %), 6/36 (16,7 %), 3/80 (3,8 %), respectively. Conclusion. This study demonstrates that the prevalence of virological failure among children and adolescents receiving ART remains high. To achieve sustained virological suppression in children and adolescents taking a protease inhibitor regimen, adherence to therapy must be increased. As one of the methods for assessing adherence, therapeutic drug monitoring can be used.

1103. Virologic and Immunologic Outcomes in People Living with HIV in a Correctional Setting During the SARS-CoV-2 Pandemic

Abstract Background It is known that the pandemic increased the risk of severe illness from SARS-CoV-2 infection in immunocompromised patients as compared to the general public. To combat this issue, telemedicine was utilized in various settings, but there is very little data on the adequate continuity of care (COC) and sustainability of telehealth throughout the pandemic. There is even less data on the effects of the pandemic in special populations, such as people living with human immunodeficiency virus (PLWH) and within the correctional setting. The purpose of this study was to investigate rates of HIV virologic suppression (VS) and the sustainability of telemedicine throughout the SARS-CoV-2 pandemic. Methods This was a retrospective, pre-post cohort study of PLWH who received antiretroviral therapy (ART) within Illinois Department of Corrections (IDOC) / University of Illinois Chicago telemedicine clinic between 3/2019 and 3/2021. Patients who were released from IDOC or reincarcerated during the study period were excluded. The primary endpoint compared the rate of HIV VS pre-, peri- and post-SARS-CoV-2 restrictions. Secondary endpoints included change in immunologic function pre-, peri- and post-SARS-CoV-2 restrictions, incidence of SARS-CoV-2 infection, number of hospitalizations, development of virologic failure, and change in ART post-pandemic. Other factors known to influence COC were also collected. Results Of 320 patients screened, 225 were included. The majority were Black males (73.7%) and 95.1% had a CD4 T-cell count &amp;gt; 200 cells/mm3 at baseline. Approximately 88% of patients were on a single tablet regimen, with most receiving bictegravir/emtricitabine/tenofovir alafenamide. Rates of HIV VS are summarized in Figure 1 and secondary outcomes are summarized in table 1. Factors associated with disruption of COC included non-adherence to appointments (62.6%) and ART (4.4%). Figure 1Rates of HIV viral suppression (&amp;lt;200 copies/mL), n(%) Table 1 Secondary outcomes Conclusion Results demonstrated that PLWH within IDOC had sustained VS and COC throughout the SARS-CoV-2 pandemic with telemedicine. These results describe how the pandemic impacted PLWH in a correctional setting and future studies could contribute to creating national guidance for telemedicine models to streamline clinical practice. Disclosures All Authors: No reported disclosures.

1278. Real World Treatment Experience of Single Tablet Dolutegravir/Lamivudine in Those Naïve to Treatment with Baseline Viral Loads ≥ 100,000 copies/mL in the US

Abstract Background Treatment for people living with HIV-1 (PLWH) continues to advance with a two-drug regimen (2DR) approach. Dolutegravir/lamivudine (DTG/3TC) is indicated as a 2DR for both treatment-naïve and virally suppressed PLWH. Despite high and sustained virologic efficacy for DTG-based 2DRs observed in clinical trials, there is limited evidence in US real world clinical settings. This study characterizes prescribing behaviors and treatment outcomes for DTG-based 2DR in the real world. Methods TANDEM was a retrospective medical chart review conducted across 24 US sites. Eligible PLWH were adults initiated on single tablet DTG/3TC or DTG/rilpivirine prior to Sept/30/2020 with a minimum clinical follow-up of six months. Treatment-naïve PLWH had no prior history of HIV therapy. Clinical characteristics, treatment history and outcomes were abstracted. Analyses were descriptive. Reported here are viral outcomes for the DTG/3TC cohort of treatment-naïve PLWH with baseline viral loads (VLs) ≥ 100,000 (c/mL). Results From an overall sample of 469 PLWH on DTG-based 2DR, 318 received DTG/3TC. Of the DTG/3TC cohort, 126 were treatment-naïve. Of the treatment-naïve, 58 PLWH had known VLs available at DTG/3TC initiation. For those with baseline VLs ≥ 100,000 c/mL, 9 had values 100,000-250,000 c/mL while 7 were &amp;gt; 250,000 c/mL. Characteristics of this sub-cohort are described in Table 1. Overall, the most common reason for DTG/3TC initiation in this sub-cohort was patient preference (n=5), followed by avoidance of long-term toxicities and convenience (both n=3). For those with VLs between 100-250k, median CD4 count was 312 while 8/9 became virally suppressed (HIV-1 RNA &amp;lt; 50c/mL) and 1 PLWH had missing data. For those with VLs &amp;gt; 250k, median CD4 count was 114 while 6/7 became virally suppressed and 1 PLWH had missing data. One of these 6 PLWH experienced virologic rebound yet remained on DTG/3TC. Table 1:Clinical Characteristics Conclusion These real world results reflect data from clinical trials, demonstrating DTG/3TC is effective and well tolerated in the real world. Nearly all DTG/3TC users, regardless of baseline VL, experienced sustained virologic suppression with few treatment discontinuations. Caution should be used when extrapolating these results due to limited population size of the sub-cohorts. Disclosures Paul Benson, DO, AAHIVS, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Speakers Bureau and Advisory Boards Cindy Donovan, PharmD, Johnson &amp; Johnson: Stocks/Bonds|ViiV Healthcare: Employee/Salary|ViiV Healthcare: Stocks/Bonds Gavin Harper, BA, ViiV Healthcare: Adelphi Real World were paid consultants (CRO) to conduct the observational research study on behalf of ViiV Healthcare.|ViiV Healthcare: Adelphi Real World were paid consultants (CRO) to conduct the observational research study on behalf of ViiV Healthcare Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Salaried employee|ViiV Healthcare: Stocks/Bonds Katie L. Mycock, MChem, ViiV Healthcare: Adelphi Real World were paid consultants (CRO) to conduct the observational research study on behalf of ViiV Healthcare|ViiV Healthcare: Adelphi Real World were paid consultants (CRO) to conduct the observational research study on behalf of ViiV Healthcare Alan Oglesby, MPH, GlaxoSmithKline (GSK): Employment|GlaxoSmithKline (GSK): Stocks/Bonds Jimena Patarroyo, PharmD, AAHIVP, ViiV Healthcare: Salaried employee|ViiV Healthcare: Stocks/Bonds|ViiV Healthcare: Stocks/Bonds Aimee Metzner, PharmD, AAHIVP, ViiV Healthcare: Salaried employee|ViiV Healthcare: Stocks/Bonds.

Missed opportunities for HIV counselling and testing service delivery among pregnant women in Nigeria: Evidence from the 2018 National nutrition and health survey.

According to UNAIDS, the 90-90-90 strategy calls for 90% of HIV-infected individuals to be diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and 90% of whom will achieve sustained virologic suppression. HIV counselling and testing (HCT) is an important entry point for effective prevention of mother-to-child transmission of HIV. However, evidence abounds that HCT is often missed by pregnant women during antenatal care in Nigeria. We used secondary data from the 2018 Nigerian National Nutrition and Health Survey (NNHS) to determine the pattern of missed opportunities within the HCT algorithm and the factors associated with the missed opportunities. Of the 8,329 eligible women, 2,327 (27.9%) missed HCT because of lack of antenatal care; 1,493 (24.9%) missed HIV pre-test counselling; 180 (4.0%) missed HIV testing after participating in pre-test counselling, while 793 (18.2%) missed collection of HIV result and post-test counselling. Generally, most of the women that missed HCT were from the North West (43.3%) and had their antenatal care with traditional birth attendants. The odds of missing ANC were higher in women in the Northern and Southern regions. Concerning pre-test HIV counselling, the odds of missing it were higher among women in the Northwest and Southeast while the odds of missing post-test counselling of HIV test were higher among women in the Northeast and Southeast relative to other regions. Using TBA as a care provider was associated with higher odds of women missing pre-test and post-test counselling of HIV during ANC compared to those that used doctors or midwives or CHEWs. Missed opportunities are common in different stages of HIV counselling and testing pathway in Nigeria, particularly in the Northern regions. Future studies would need to identify the specific reasons for these missed opportunities, enabling the targeting of more specific policy reform and interventions.

Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth.

The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.

Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale.

Tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy program in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care simplified amplification-based assays (Diagnostics for the Real World, Sunnyvale, CA, USA) at Chidamoyo Christian Hospital and rate of virological suppression (VS) on TLD (VL <1,000 copies/mL) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median [interquartile range (IQR)] age was 15 (11-19) years, above half of the participants were female (57%). Before switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ≥1,000 copies/mL on TLD, 90% (9/10) were failing on their previous regimens, 6 of 9 (67%) having been on boosted protease inhibitor-based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virological failure and emergence of resistance in Africa. However, longer follow-up might be needed to ascertain sustained VS in this vulnerable population. Randomized Control Trial NCT03986099.

Can simplified antiretroviral drug combination therapies resist resistance?

Can simplified antiretroviral drug combination therapies resist resistance?

Combination anti-HIV antibodies provide sustained virological suppression.

Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)1. However, eradication of the virus in individuals with HIV has not been possible to date2. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication3. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24 weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43 weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.

Kinetics in HBsAg after Stopping Entecavir or Tenofovir in Patients with Virological Relapse but Not Clinical Relapse.

This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders.

Determinants of suboptimal immune recovery among a Chinese Yi ethnicity population with sustained HIV suppression

ObjectivesDespite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence.MethodsThis retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/μL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery.ResultsThere were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/μL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/μL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients.ConclusionsOur study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART.Trial registration None