Viral Blips Research Articles

High efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in Black adults in the United States, including those with pre-existing HIV resistance and suboptimal adherence.

BRAAVE (NCT03631732), a Phase 3b, multicenter, open-label US study, demonstrated the efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) among Black individuals with suppressed HIV through 48 weeks. Here, 72-week resistance, adherence, and virologic outcomes are presented. Enrollment criteria permitted nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistance (R), protease inhibitor (PI)-R, and certain nucleos(t)ide reverse transcriptase inhibitor (NRTI)-R (M184V/I allowed; ≥3 thymidine analog mutations [TAMs] excluded); but excluded primary integrase strand transfer inhibitor (INSTI)-R. Pre-existing resistance was determined using historical genotypes and retrospective baseline proviral DNA genotyping. Adherence, virologic outcomes, and viral blips were assessed. Of 489 participants receiving B/F/TAF with ≥1 post-switch HIV-1 RNA measurement: pre-existing NRTI-R (15% of participants), M184V/I (11%), ≥1 TAMs (8%), NNRTI-R (22%), and PI-R (13%) were observed; pre-existing INSTI-R substitutions (2%) were detected post-randomization; mean viral blip frequency was 0.9% across all timepoints (unassociated with virologic failure); 24% of participants had <95% adherence (98% of whom had HIV-1 RNA<50 copies/mL at last visit); none had treatment-emergent study-drug resistance. Overall, 99% of participants, including all with baseline NRTI-R/INSTI-R, had HIV-1 RNA<50 copies/mL at the last visit, demonstrating that B/F/TAF maintained virologic suppression through 72 weeks regardless of pre-existing resistance, viral blips, and suboptimal adherence.

Chemsex and rising substance use linked to sexually transmitted infections among men who have sex with men living with HIV in Bangkok, Thailand

ObjectivesWe report longitudinal trends in alcohol and recreational drug use, and their associations with sexual behaviors and clinical outcomes in a Thai cohort of predominantly men who have sex with men (MSM) living with HIV. MethodsFrom 2017 to 2019, participants in the RV254/SEARCH010 acute HIV cohort answered questions every 24 weeks about drug use and sexual behaviors. Longitudinal trends were assessed using the χ2 test for trend. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with recreational drug and alcohol use. ResultsAmong 604 participants, the median age was 26 (interquartile range 23-31) years, and 93.5% were MSM. Alcohol consumption was reported in 83.3% and recreational drug use in 46.9% during the study period, with rising trends in both over the years. Participants who reported recreational drug use were more likely to have hepatitis C (OR 3.42, 95% CI 1.88-6.21), syphilis (OR 2.69, 1.75-4.13), gonorrhea (OR 7.74, 5.04-11.89), and chlamydia (OR 1.61, 1.12-2.31), and to engage in group sex (OR 7.74, 5.04-11.89). Participants who used any recreational drugs had more frequent viral blips (23.1% vs 14.2%, P = 0.007) and reported missed doses of antiretroviral drugs more often (52.4% vs 36.9%, P <0.001), but had no significant difference in viral suppression (94.1% vs 97.4%, P = 0.06). ConclusionsAmong MSM living with HIV in Bangkok, recreational drug use has increased in recent years and was associated with hepatitis C and sexually transmitted infections, especially among men who participate in group sex. Prevention strategies and other interventions may improve treatment adherence and other HIV outcomes.

Low Level Viremia Is Associated With Serious non-AIDS Events in People With HIV.

The consequences of low-level viremia in people with HIV are unclear. We used data from the US Military HIV Natural History Study to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs). Included participants initiated antiretroviral therapy after 1996 and had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after antiretroviral therapy initiation. VLs were categorized as lower levels of LLV (51-199 copies/mL), higher level of low-level viremia (HLLV; 200-999 copies/mL), and (VF; ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS; ie, VL <50 copies/mL). Viral blips (ie, VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL) were analyzed in the VS category. Cox proportional hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% confidence intervals are presented. A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3 [1.2-1.4]), HLLV (1.6 [1.5-1.7]), and virologic failure (1.7 [1.7-1.8]). The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.

1573. Viral Blips While on Antiretroviral Therapy are Associated with Virologic Failure

Abstract Background Blips in HIV viral load (VL) while on antiretroviral therapy (ART) are of unclear clinical significance. In this study, we examined the association between blips and virologic failure (VF). Methods We used data from the US Military HIV Natural History Study (NHS) cohort. Included participants were diagnosed with HIV after 2006, had been on ART for ≥ 6months, and had ≥3 VLs recorded and measured using an assay with a lower limit of detection of &amp;lt; 50 copies/mL. VF was defined as two consecutive VLs ≥ 200 copies/mL spanning 90 days or a single VL ≥1000 copies/mL. Blips were defined as VL of 51-999 copies/mL, that were preceded and followed by a VL ≤ 50 copies/mL and were differentiated by magnitude as low-level (VL 51-199 copies/mL) or high-level (200-999 copies/mL). Detectable VLs that did not meet criteria for VF or blips were grouped as low-level viremia (LLV; 51-199 copies/mL), and higher low-level viremia (hLLV; 200-999 copies/mL). Cox proportional hazards models adjusted for demographic characteristics, time updated CD4 counts, ART, and viral load were used. Hazard ratios and 95% confidence intervals are presented. Results A total of 988 participants (median age 34.1 years, 96.7% male, 41.7% African American) were included, of which 55 (5.6%) experienced VF (Table 1). While 191 participants (19.3%) experienced blips, it was the highest VL status in 146 (14.8%) (Table 2). Having blips and low-level viremia was associated with increasing hazard of VF, graded by type and level of viremia (low-level blip 1.86 [1.10 – 3.14]; high-level blip 3.56 [1.13 – 11.18]; LLV 4.10 [3.06-5.51]; hLLV 10.51 [6.28-17.61]. Other factors associated with VF were African American race and higher VL at ART initiation. Whereas higher CD4 counts, and use of integrase strand transfer inhibitors (relative to Non-Nucleoside Reverse Transcriptase inhibitors) were protective (Table 3). Conclusion Detectable viremia, including blips, are associated with an increased risk of VF. The magnitude of the viremia appears important with dose-response-type impact (i.e., viral loads &amp;gt;200 copies/mL having a greater hazard of VF). These findings suggest that individuals with viral blips at a minimum should undergo evaluation for medication adherence and may benefit from more frequent VL monitoring. Disclosures All Authors: No reported disclosures

Investigating rates and predictors of viral blips, low-level viraemia and virological failure in the Australian HIV observational database.

Australia has made significant progress towards achieving the UNAIDS's 95-95-95 cascade targets including HIV viral suppression. To investigate the burden of HIV viraemia, we assessed viral blips, low-level viraemia (LLV) and virologic failure (VF) in an Australian cohort. We studied the proportion of people with viral suppression, viral blips, LLV and VF in the Australian HIV observational database (AHOD) between 2010 and 2021. The association between blips or LLV, and VF was investigated using Cox regression, and predictors of viral blips and LLV were assessed using repeated-measured logistic regression. Among 2544 AHOD participants who were in follow-up and on antiretroviral therapy (ART) from 1 January 2010 (88.7% male), 444 had experienced VF (incidence rate: 2.45 [95% CI: 2.23-2.69] per 100 person-years [PY]) during 18,125 PY of follow-up (a median of 7.6 years). The proportion of people with VF decreased over time, whereas rates of blips and LLV remained stable. Participants with blips (hazard ratio, 2.89; 95% CI: 2.31-3.61) and LLV (4.46; 95% CI: 3.38-5.89) were at increased risk of VF. Hepatitis B co-infection, longer documented treatment interruption duration, younger age and lower CD4 at ART initiation, and protease inhibitors-based initial regimen were associated with an increased risk of VF. Common predictors of blips and LLV such as higher HIV-1 RNA and lower CD4 at ART initiation, longer treatment interruption, more VL testing and types of care settings (hospitals vs. sexual health services) were identified. Blips and LLV predict subsequent VF development. We identified important predictors of HIV viraemia including VF among individuals on INSTI-based regimens to help direct HIV management plans.

The impact of the M184V resistance mutation on treatment outcomes in patients with HIV infection: a systematic review and meta-analysis.

HIV is a global deliberating infectious disease. Of note, more than 36 million people living with HIV (PLHIV) with approximately newly diagnosed 1.5 million cases annually. M184V is a single base mutation in the highly conserved YMDD domain of reverse transcriptase (RT). It is one of the most encountered resistances associated with mutations to nucleoside RT inhibitors. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in PLHIV. Therefore, the present systematic review was executed to reveal the virological failure, virological suppression, and resistance to antiretroviral therapy (ART) regimens in PLHIV with the M184V mutation. All clinical studies comparing the treatment outcomes among PLHIV harboring or not harboring M184V mutation were appropriate for systematic review and meta-analysis. The present systematic review included six articles, encompassing 4760 PLHIV. Of them, 1222 (25.67%) patients had M184V mutation, while 3538 (74.32%) PLHIV did not. The meta-analysis showed that patients with M184V mutation were 1.87 times more liable to virological failure (risk ratio [RR] 1.87; 95% 1.09, 3.20; p = 0.02). Furthermore, pooling the data from two studies revealed a significantly higher risk of viral blips (RR 2.26; 95% 1.47, 3.46; p = 0.0002). Concerning discontinuation of ART, there was no statistical difference between patients with and without M184V mutation (RR: 0.99; 95% 0.78, 1.25; p = 0.90). The present study revealed the negative impact of the M184V mutation on treatment outcomes in PLHIV. This included a higher risk of virological failure and viral blips, relative to patients without the mutation. Such patients may benefit from more aggressive and combined therapy for better disease management.

Mathematical Models of HIV-1 Dynamics, Transcription, and Latency.

HIV-1 latency is a major barrier to curing infections with antiretroviral therapy and, consequently, to eliminating the disease globally. The establishment, maintenance, and potential clearance of latent infection are complex dynamic processes and can be best described with the help of mathematical models followed by experimental validation. Here, we review the use of viral dynamics models for HIV-1, with a focus on applications to the latent reservoir. Such models have been used to explain the multi-phasic decay of viral load during antiretroviral therapy, the early seeding of the latent reservoir during acute infection and the limited inflow during treatment, the dynamics of viral blips, and the phenomenon of post-treatment control. Finally, we discuss that mathematical models have been used to predict the efficacy of potential HIV-1 cure strategies, such as latency-reversing agents, early treatment initiation, or gene therapies, and to provide guidance for designing trials of these novel interventions.

Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study.

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010-2020 consisting of two nucleos(-t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50-499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non-adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI- (n = 5119; 20.9%), PI- (n = 8935; 36.4%), and NNRTI-use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non-blip VLs were RNAneg (no RV) (n = 15 326; 63.4%), 1-19 cp/mL (n = 6318; 26.1%), 20-49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNAneg in all VLs assessed. RV 1-19 cp/mL and 20-49 cp/mL (vs. RNAneg ) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98-3.58 and 3.41-7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin.

Viral blips and virologic failures following mpox vaccination with MVA-BN among people with HIV.

The study aim was to evaluate whether mpox vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN) may be associated with viral blips or confirmed virologic failures (CVF) in people with HIV (PWH) receiving antiretroviral therapy and the associated factors. PWH who received MVA-BN, with HIV-RNA less than 50 copies/ml, and CD4 + lymphocytes at least 200 cells/μl in the 6 months prior to vaccination and at least 1 HIV-RNA determination within 3 months from vaccination. The primary outcome was occurrence of viral blips (1 HIV-RNA ≥50 copies/ml) and CVF (1 HIV-RNA ≥1000 copies/ml or ≥2 consecutive HIV-RNA ≥50 copies/ml) following MVA-BN. Changes in CD4 + and CD4 + /CD8 + were secondary outcomes. Residual viremia was defined as detectable HIV-RNA less than 50 copies/ml. PWH already vaccinated against smallpox received single-dose MVA-BN. Mann--Whitney rank-sum test or chi-square/Fisher's test applied. Overall, 187 PWH were included: 147 received two doses of MVA-BN, 40 single-dose. Six viral blips [incidence rate = 1.59/100-person months of follow-up (PMFU), 95% confidence interval (95% CI) = 0.58-3.47], and three CVFs [incidence rate = 0.80/100-PMFU (95% CI = 0.16-2.33)] were observed. Two CVFs occurred at second dose with presence of detectable HIV-RNA following first one, with high compliance to antiretroviral therapy (ART). PWH with viral blips or CVFs had, prior to first vaccination, more frequently residual viremia [77% ( n = 7) versus 35% ( n = 62), P = 0.01]. No differences in ART ( P = 0.42) and number of MBA-BN doses ( P = 0.40) was found. In two cases of CVFs, ART was changed; all VBs resolved within 1 month. Although rare, viral blips and CVFs following MVA-BN vaccination among PWH receiving ART were identified. Close monitoring of HIV-RNA during mpox vaccination should be encouraged.

Effects of Enhance Adherence Counselling on Viral Load Suppression Among High Viral Load HIV Seropositive Patients in a Nigerian Tertiary Health Facility

Background: EAC helps clients overcome adherence hurdles and improve ART adherence. This study examines the effect of EAC on viral load suppression. Method: This quantitative study aims to determine the impacts of enhanced adherence counselling (EAC) on viral load in Defence Headquarters Medical Center, Abuja, Nigeria. The medical records of HIV clients on ART included in EAC were extracted from the hospital and analyzed to determine the impacts of EAC on viral loads suppression of clients in the program. Result: Almost half of the PLWHIV in EAC have been on ART for 6-10 years (47.6%), 42.9% for more than ten years, and 9.5% have been on ART for 1 – 5 years. 76.2% of respondents were on the 1st line of the ART regimen, while 23.8% were on the 2nd line. 97.6% of clients enrolled for EAC were at the WHO stage I HIV infection, and only one (2.4%) was in stage IV. 50% tested for viral load was due to viral blip, 28.6% due to unsuppressed viral load and 21.4% were tested to monitor their VL. Furthermore, of the 33 clients with viral load results, 14 (42.4%) had very low-level viremia (&lt;50 copies/ml), 10 (30.3%) had low-level viremia (50–1000 copies/ml), but 9 (27.3%) still had high-level viremia (&gt;1000 copies/ml). 42.9% enrolled for EAC because of pill burdens, 31.0% due to irregular dosing frequency, 19.0% because of pill social problems, and 2.1% were people lost to follow-up returned.. Keywords: Antiretroviral therapy, EAC, Viral load.

Outcomes of Bariatric Surgery in People With Human Immunodeficiency Virus: A Retrospective Analysis From the ATHENA Cohort.

The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown. Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS. Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of -33.5% (-37.7% to -29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P < .01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS. BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes.

TLR7 Agonist GS-9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIVSF162P3-Infected Rhesus Monkeys.

Antiretroviral therapy is capable of inhibiting HIV replication, but it fails to completely achieve a cure due to HIV persistence. The commonly used HIV cure approach is the "shock and kill" strategy, which employs latency-reversing agents to trigger viral reactivation and boost cellular immunity. Finding the appropriate drug combination for the "shock and kill" strategy would greatly facilitate clinical trials. The toll-like receptor (TLR) 7 agonist GS-9620 and nicotinamide (NAM) are reported as potential latency-reversing agents. Herein, we found the absence of viral reactivation when SHIVSF162P3-aviremic rhesus macaques were treated with GS-9620 monotherapy. However, our findings demonstrate that viral blips emerged in half of the macaques treated with the combination therapy of GS-9620 and NAM. Notably, an increase in the reactivation of the replication-competent latent virus was measured in monkeys treated with the combination therapy. These findings suggest that the GS-9620 and NAM combination could be used as a multipronged HIV latency stimulation approach, with potential for optimizing antiviral therapy design.

Strong Resonance Bifurcations in a Discrete-Time In-Host Model With a Saturating Infection Rate

Abstract Viral blips are a recurrent pattern observed in many persistent infections such as the human immunodeficiency virus (HIV). The main goal of this research is to present a comprehensive analytical study of a two-dimensional discrete-time in-host infection model, that exhibits viral blips, with a saturating infection rate. We examine the interactions between the population densities of infected and uninfected CD4+ T cells by discussing the model's dynamics in the long run. The local asymptotic stability of fixed points of the model is investigated. The model undergoes both flip and Neimark–Sacker bifurcations. Moreover, codimension-two bifurcations of the endemic fixed point are discussed using bifurcation theory and normal forms. The model exhibits 1:2, 1:3, and 1:4 strong resonances. Numerical simulations are performed to verify our analysis. In addition, bifurcations of higher iterations are extracted from the numerical continuation.

Cohort profile: a longitudinal study of HIV infection in the central nervous system with focus on cerebrospinal fluid – the Gothenburg HIV CSF Study Cohort

PurposeIn order to enable long-term follow-up of the natural course of HIV infection in the central nervous system, a longitudinal cohort study with repeated cerebrospinal fluid (CSF) analyses at intervals...

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Does menopause transition influence viral suppression and adherence in Women living with HIV?

Increasing numbers of women living with HIV transition through menopause. It is unclear if this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU). Retrospective Swiss HIV Cohort Study analysis from 01/2010 to 12/2018. We explored peri- and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities and IDU using interrupted time series (ITS) models. Rates of depression and psychiatric care increased during perimenopause before decreasing afterwards. Negative treatment outcomes such as viral blips, low-level viremia, viral failure and low adherence steadily declined while transitioning through menopause - this was also true for subgroups of women with depression, psychiatric treatment and active IDU. Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland.

HIV Virologic Failure among Patients with Persistent Low-Level Viremia in Nairobi, Kenya: It Is Time to Review the >1000 Virologic Failure Threshold.

Persistent low-level viremia (PLLV) of 200-999 copies/ml has been reported as a risk factor for HIV virologic failure (VF). This retrospective study was aimed at characterizing patients with PLLV, determining factors associated with VF, and determining the effect of regimen change. Data were extracted from electronic medical records for HIV care and treatment. Patients' characteristics (N = 705) were as follows: a mean age of 42 years, majority female (55%), and 51% married. A majority (78.7%) had a history of opportunistic infections in their ART lifetime. To determine factors associated with VF, 187 records on patients who maintained PLLV and 12 on deceased patients at the time of data review were eliminated from the analysis, leaving 506 patient records. Out of the 506, 89% (451/506) suppressed VL to nondetectable levels while 11% (55/506) had VF, and the difference was significant (P = 0.0001). Virologic failure was significantly associated with ages 10-30 years (P < 0.05). Baseline VL ≥ 1000 (OR 3.929; P = 0.002) and 200-999 copies/ml (OR 4.062; P = 0.004) were associated with VF. During PLLV, factors associated with VF included the following: PLLV of 200-999 copies/ml (P < 0.05), viral blips (OR 4.545; P = 0.0001), mean maximum VL (P < 0.05), and age (P = 0.043). Married marital status was inversely associated with VF (OR 0.318; P = 0.026). Regimen change was not significantly associated with virologic outcomes. However, patients who switched regimens to the second line had a high risk of VF (P = 0.028; OR 3.203). Regimen change was significantly high (P < 0.05) among adolescents and patients with a start regimen of 2NRTI+1NNRTI. Most of the PLLV patients (89%) achieved nondetectable VL after their continued ART monitoring for at least 12 months. Therefore, PLLV was not an indicator of VF. However, a consistent VL of ≥200-999 copies/ml at baseline and more than 12 months of ART care and treatment were significantly associated with VF. Patients with VL 200-999 copies/ml, adolescents, and young adults require intensive ART monitoring and support.

442. Clinical Outcomes of Checkpoint Inhibitor Therapy in People with HIV: A Single-Center Case Series

Abstract Background Immunotherapeutics, particularly immune-checkpoint inhibitors (ICI), have transformed the treatment landscape for advanced cancer. Such therapies could considerably benefit people with HIV (PWH), yet PWH have often been excluded from ICI trials such that data regarding ICI safety in PWH are limited. In addition, ICIs have recently been proposed as latency reversing agents that could impact the HIV reservoir. Here, we report the outcomes in a cohort of PWH after ICI therapy. Methods Using the electronic health record, we systematically identified all PWH with advanced cancer who received ICIs from January 2000 to December 2018 at one academic medical center. We collected data on demographics, HIV history, and HIV and hematologic parameters before and after ICI in 25 PWH over 29 treatment episodes. We cataloged adverse events following treatment. Results In this cohort, ICI therapy was not associated with a significant increase in plasma HIV RNA levels nor with significant change in CD4+ T-cell count, CD8+ T-cell count, or CD4/CD8 ratio (Figure 1). Among 19 treatment episodes with available pre- and post- treatment data, there were five viral blips (26%); HIV RNA exceeded 200 copies/mL in one episode. The blip rate observed among PWH on ART in the literature ranges from 10-30% and among PWH receiving ICI from 0-33%. Adverse events included infectious and autoimmune conditions across multiple organ systems including systemic, pulmonary, gastrointestinal/hepatic, genitourinary, neurologic, endocrine, and dermatologic. The most common adverse events were diarrhea (n=7) and rash (n=5). Five deaths occurred within one month of ICI initiation; all were attributed to progressive malignancy. Figure 1:Changes in HIV parameters associated with checkpoint inhibitor therapy (a) Pretreatment plasma HIV RNA, n=23. There was one episode in which the pretreatment plasma HIV RNA was greater than 200 copies/ml. (b) Pretreatment CD4+ Tcell counts, n=24. (c) Longitudinal plasma HIV RNA trends in 5 individuals who experienced a viral blip, defined as an increase in plasma HIV RNA from “not detected” to “detected” or greater within a year of ICI initiation. Symbols represent unique participants. (d) Pretreatment and posttreatment plasma HIV RNA values closest to ICI initiation, n=19. Points are scaled to proportion of sample. (e) Pretreatment and posttreatment CD4+ T-cell counts closest to ICI initiation, n=20. Thick line represents the change in median M between the two time points. (f) Pretreatment and posttreatment CD4+ T-cell percentages closest to ICI initiation, n=19.Thick line represents the change in median M between the two time points. (g) Pretreatment and posttreatment CD8+ T-cell counts closest to ICI initiation, n=18. Thick line represents change in median M between the two time points. (h) Pretreatment and posttreatment CD4/CD8 ratios closest to ICI initiation, n=18. Thick line represents the change in median M between the two time points. Conclusion This single-center cohort demonstrated no significant impact on HIV parameters among PWH receiving ICI. This study contributes to the growing body of evidence suggesting the safety and tolerability of ICI in PWH in both HIV and non-HIV-related outcomes and supports the inclusion of PWH in future ICI clinical trials. While we did not see an increased rate of viral blips on routine clinical testing, our findings also provide key preliminary data supporting the safety and tolerability of ICIs in future studies of these agents as HIV therapeutics, for example as agents that may reverse HIV latency. Disclosures All Authors: No reported disclosures.

1264. Durability and effectiveness of fostemsavir in heavily treatment-experienced people with HIV

Abstract Background Paired with other active antiretrovirals (ARVs), fostemsavir (FTR) may offer heavily treatment-experienced (HTE) people with HIV (PWH) options for continuing effective treatment. Durability and effectiveness of FTR-containing regimens in routine clinical care in the United States were assessed. Methods Electronic health record data from the OPERA® cohort were used to identify adults initiating FTR-containing regimens between 2JUL2020 (FDA approval) and 1SEP2021. Eligible PWH were followed from first FTR prescription (baseline) until FTR discontinuation, death, loss to follow up, or study end (28FEB2022). Durability was assessed as frequency of FTR discontinuation. Virologic outcomes assessed at 6 and 12 months (±3 months) included suppression (viral load [VL] &amp;lt; 50 copies/mL), virologic failure (2 consecutive VL ≥200 copies/mL or 1 VL ≥200 copies/mL + FTR discontinuation within 120 days after suppression), and viral blips (1 VL ≥50 copies/mL preceded and followed by VLs &amp;lt; 50 copies/mL). Analyses were stratified by baseline viral load (bVL &amp;lt; 50 copies/mL; bVL ≥50 copies/mL). Results Overall, 86 PWH initiated FTR (bVL &amp;lt; 50: 30; bVL ≥50: 55), with median follow up of 10.8 months (IQR: 6.8, 15.3). Compared to PWH with bVL ≥50, those with bVL &amp;lt; 50 were older and more likely to be white and have lived longer with HIV (Table 1). Over follow up, 20% discontinued FTR (Table 2). Most (82%) FTR discontinuations were switches to alternative regimens; the remaining were ARV interruptions (no ARVs for &amp;gt; 45 days). Among PWH with bVL &amp;lt; 50, most maintained suppression (6 months: 74%; 12 months: 82%; Figure). Among PWH with bVL ≥50 and with follow up VL during the period assessed, 33% were suppressed at 6 months, 36% were suppressed at 12 months, and 48% achieved suppression at any time over the entire follow up (Figure). In either group, ≤5 PWH experienced virologic failure or blip, though the proportion of PWH with multiple follow up VLs was low. Conclusion Despite a heterogenous population and diverse regimens, most HTE PWH remained on FTR at study end. Most PWH with bVL &amp;lt; 50 remained suppressed and half of PWH with bVL ≥50 achieved suppression over the entire study period. Virologic failure and blips were infrequent, although follow up was limited in this early evaluation of real-world FTR use. Disclosures Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Clark, MD, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds Gerald Pierone, Jr., MD, Gilead: Grant/Research Support|GSK-VIIV: Grant/Research Support Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck &amp; Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

BackgroundThe use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC).MethodsThis is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy.Results218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3–67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients’ decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483–927). After 5 years it raised to 899 cells/mcl (IQR 646–1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532–1034) to 683 cells/mcl (IQR 538–988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60–1.30) to 1.15 (IQR 0.77–1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up.ConclusionThese long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH.