Sustained Viral Suppression Research Articles

HIV reservoir and premature aging: risk factors for aging-associated illnesses in adolescents and young adults with perinatally acquired HIV.

Despite receiving antiretroviral therapy (ART), an increasing number of adolescents and young adults with perinatally acquired HIV (PHIVAYA) are at risk of developing premature senescence and aging-associated illnesses, including cancer. Given this concern, it is crucial to assess aging biomarkers and their correlation with the HIV reservoir in order to comprehensively characterize and monitor these individuals. Fifty-five PHIVAYA (median age: 23, interquartile range [IQR]: 20-27 years, and 21 [18-23] years on ART at the time of study sampling) were studied along with 23 age-matched healthy controls. The PHIVAYA exhibited significantly higher percentages of activated, senescent, exhausted CD4 and CD8 T cells, shorter telomeres, reduced thymic output, and higher levels of circulating inflammatory markers (PAMPs, DAMPs, and pro-inflammatory cytokines IL-6, IL-8, and TNFα) as well as denervation biomarkers (neural cell adhesion molecule 1 [NCAM1] and C-terminal Agrin fragment [CAF]), compared to controls. HIV-DNA levels positively correlated with activated, senescent, exhausted CD4 and CD8 T cells, circulating biomarkers levels, and inversely with regulatory T and B cells and telomere length. According to their viremia over time, PHIVAYA were subgrouped into 14 Not Suppressed (NS)-PHIVAYA and 41 Suppressed (S)-PHIVAYA, of whom 6 who initiated ART within one year of age and maintained sustained viral suppression overtime were defined as Early Suppressed (ES)-PHIVAYA and the other 35 as Late Suppressed (LS)-PHIVAYA. ES-PHIVAYA exhibited significantly lower HIV-DNA reservoir, decreased percentages of senescent and exhausted CD4 and CD8 T cells, reduced levels of circulating inflammatory and denervation biomarkers, but longer telomere compared to LS- and NS-PHIVAYA. They differed significantly from healthy controls only in a few markers, including higher percentages of regulatory T and B cells, and higher levels of DAMPs. Overall, these results underscore the importance of initiating ART early and maintaining viral suppression to limit the establishment of the viral reservoir and to counteract immune and cellular premature aging. These findings also suggest new approaches for minimally invasive monitoring of individuals at high risk of developing premature aging and age-related illnesses.

Efficacy and safety of two fixed doses of ibalizumab plus optimized background regimen in treatment-experienced HIV-positive individuals.

Sustained viral suppression in patients with multidrug-resistant (MDR) human immunodeficiency virus (HIV) infection remains difficult; accordingly, agents targeting different steps in the HIV life cycle are needed. Ibalizumab, a humanized immunoglobulin G4 monoclonal antibody, is a cluster of differentiation (CD4)-directed post-attachment inhibitor. In this Phase IIb study, 113 individuals with MDR HIV-1 and limited treatment options were assigned an optimized background regimen (OBR) and randomized to either 800 mg ibalizumab every two weeks (q2wk; n=59) or 2,000 mg ibalizumab every four weeks (q4wk; n=54) up to Week 24. Viral loads (VL) below the detection limit were achieved in 44% and 28% of patients in the 800 mg q2wk and 2,000 mg q4wk groups, respectively, at Week 24. Mean (standard deviation) VL (log10 copies/mL) decreased from Baseline (4.6(0.8), 800 mg q2wk; 4.7(0.7), 2,000 mg q4wk) to Week 2, with the reduction maintained through Week 24 (2.9(1.5), 800 mg q2wk; 3.2(1.4), 2,000 mg q4wk). Baseline CD4+ counts were 80.5 and 54.0 cells/μL in the 800 mg q2wk and 2,000 mg q4wk groups, respectively. Mean CD4+ T-cell count was increased at Week 24 in both groups. No serious adverse events were related to ibalizumab. In heavily treatment-experienced patients with HIV (PWH) at a more advanced baseline disease severity, clinically significant response rates at Week 24 were achieved with ibalizumab plus OBR. Ibalizumab's unique mechanism of action and lack of cross-resistance to other antiretroviral agents make it an important component of combination treatment regimens for PWH with limited treatment options.

Trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio in patients with HIV and long-term virological suppression based on Yunnan HIV cohort.

Our objective was to evaluate the trajectory of immunology in patients with HIV with different baseline CD4 T-cell count strata after antiretroviral therapy (ART) under long-term viral suppression. This was a sub-analysis focused on patients with virological suppression for at least 5 years after ART. Data were obtained from the Yunnan HIV cohort in China. Patients were categorized according to prespecified baseline CD4 T-cell counts. The trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio changing over time were fitted using a B-spline regression model. The Cox proportional hazards regression model was used to assess the association of baseline CD4 T-cell count with the risk of both immunological responder (IR) and CD4/CD8 ratio normalization. A total of 2618 patients with a median follow-up of 7.25 years (interquartile range [IQR] 5.92-8.75) were included. Over a period of 12 years, the mean CD4 T-cell count remained above 500 cells/μL in all groups. The mean CD4/CD8 ratio was solely normalized in patients whose baseline CD4 T-cell counts were above 350 cells/μL. Patients with higher baseline CD4 T-cell counts showed higher risks of both IR and CD4/CD8 ratio normalization than those with the lowest (all p trend <0.001). A higher baseline CD4 T-cell count predicted a shorter time for both IR and CD4/CD8 ratio normalization. Long-term, sustained viral suppression may not be able to fully normalize immunological functions in patients with HIV. A high baseline CD4 T-cell count benefits IR and CD4/CD8 ratio normalization.

HIV/AIDS public health resource allocation policy and its optimization in the United States

With 38 million HIV-positive individuals living worldwide, HIV/AIDS is a fatal and rigorous threat to build up a global health society. It is critical to optimize the allocation of public health resources for improving the life quality of HIV/AIDS patients in the U.S. Meanwhile, the inevitable mission of confirming HIV diagnosis receive comprehensive care, reduce HIV disparities among marginalized populations, and implement effective prevention measures. This article analyzes the allocation of public health resources for HIV/AIDS in the United States, including key issues such as funding allocation, medical infrastructure, targeted interventions, and health equity. A thorough assessment of the affordability of HIV-related medical services and their interventions' efficacy is executed. At the same time, this article also focuses on the effectiveness of PrEP. Although PrEP has been proven to be effective, its promotion still faces problems such as insufficient awareness, financial barriers, limited access, and social stigma. To address these challenges, it is necessary to strengthen public education, train medical providers, reduce PrEP costs, expand access, and combat stigma through public awareness campaigns and legal protection. This comprehensive approach is consistent with a broader public health strategy aimed at slowing HIV transmission and achieving sustained viral suppression.

Lower Neutrophil Count Without Clinical Consequence Among Children of African Ancestry Living With HIV in Canada.

To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry. We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across 8 Canadian pediatric HIV care centers. We classified CLWH according to African ancestry, defined as "African," "Caribbean," or "Black" maternal race. Longitudinal laboratory data (white blood cells, neutrophils, lymphocytes, viral load, and CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, and treatments) were abstracted from medical records. Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, white blood cell counts, and neutrophil-lymphocyte ratios. Neutrophil count <1.5 × 109/L was detected in 60% of CLWH of African ancestry, compared with 31% of CLWH of non-African ancestry (P < 0.0001), representing a 2.0-fold higher relative frequency (95% CI: 1.4-2.9). Neutrophil count was on average 0.74 × 109/L (95% CI: 0.45 to 1.0) lower in CLWH of African ancestry (P < 0.0001). Neither neutrophil count<1.5 × 109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, and lifetime nadir CD4). In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions.

Enhancements to the National HIV Surveillance System, United States, 2013-2023.

HIV infection is monitored through the National HIV Surveillance System (NHSS) to help improve the health of people with HIV and reduce transmission. NHSS data are routinely used at federal, state, and local levels to monitor the distribution and transmission of HIV, plan and evaluate prevention and care programs, allocate resources, inform policy development, and identify and respond to rapid transmission in the United States. We describe the expanded use of HIV surveillance data since the 2013 NHSS status update, during which time the Centers for Disease Control and Prevention (CDC) coordinated to revise the HIV surveillance case definition to support the detection of early infection and reporting of laboratory data, expanded data collection to include information on sexual orientation and gender identity, enhanced data deduplication processes to improve quality, and expanded reporting to include social determinants of health and health equity measures. CDC maximized the effects of federal funding by integrating funding for HIV prevention and surveillance into a single program; the integration of program funding has expanded the use of HIV surveillance data and strengthened surveillance, resulting in enhanced cluster response capacity and intensified data-to-care activities to ensure sustained viral suppression. NHSS data serve as the primary source for monitoring HIV trends and progress toward achieving national initiatives, including the US Department of Health and Human Services' Ending the HIV Epidemic in the United States initiative, the White House's National HIV/AIDS Strategy (2022-2025), and Healthy People 2030. The NHSS will continue to modernize, adapt, and broaden its scope as the need for high-quality HIV surveillance data remains.

Infant Feeding for Persons Living With and at Risk for HIV in the United States: Clinical Report.

Pediatricians and pediatric health care professionals caring for infants born to people living with and at risk for HIV infection are likely to be involved in providing guidance on recommended infant feeding practices. Care team members need to be aware of the HIV transmission risk from breastfeeding and the recommendations for feeding infants with perinatal HIV exposure in the United States. The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%. The American Academy of Pediatrics recommends that for people with HIV in the United States, avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission. However, people with HIV may express a desire to breastfeed, and pediatricians should be prepared to offer a family-centered, nonjudgmental, harm reduction approach to support people with HIV on ART with sustained viral suppression below 50 copies per mL who desire to breastfeed. Pediatric health care professionals who counsel people with HIV who are not on ART or who are on ART but without viral suppression should recommend against breastfeeding. Pediatric health care professionals should recommend HIV testing for all pregnant persons and HIV preexposure prophylaxis to pregnant or breastfeeding persons who test negative for HIV but are at high risk of HIV acquisition.

Prevalence of Diagnosed and Undiagnosed Depression Among US Adults with Human Immunodeficiency Virus: Data from the Medical Monitoring Project.

People with human immunodeficiency virus (PWH) are disproportionately affected by depression, but the recent national estimates for US PWH encompassing both current symptoms and clinical diagnoses to assess missed diagnoses and lack of symptom remission are lacking. We used data from CDC's Medical Monitoring Project (MMP) to report nationally representative estimates of diagnosed and undiagnosed depression among US adult PWH. During June 2021 to May 2022, MMP collected interview data on symptoms consistent with major or other depression and depression diagnoses from medical records of 3928 PWH. We report weighted percentages and prevalence ratios (PRs) to quantify differences between groups on key social and health factors. Overall, 34% of PWH experienced any depression (diagnosis or Patient Health Questionnaire-8); of these, 26% had symptoms but no diagnosis (undiagnosed depression), 19% had both diagnosis and symptoms, and 55% had a diagnosis without symptoms. Among those with depression, persons with a disability (PR: 1.52) and food insecurity (PR: 1.67) were more likely to be undiagnosed. Unemployed persons (PR: 1.62), those experiencing a disability (PR: 2.78), food insecurity (PR: 1.46), or discrimination in human immunodeficiency virus (HIV) care (PR: 1.71) were more likely to have diagnosed depression with symptoms. Those with symptoms (undiagnosed or diagnosed) were less likely to be antiretroviral therapy (ART) dose adherent (PR: 0.88; PR: 0.73) or have sustained viral suppression (PR: 0.62; PR: 0.91) and were more likely to have unmet needs for mental health services (PR: 2.38, PR: 2.03). One-third of PWH experienced depression, of whom nearly half were undiagnosed or still experiencing clinically relevant symptoms. Expanding screening and effective treatment for depression could improve quality of life and HIV outcomes.

Peers plus mobile app for treatment in HIV (PATH): protocol for a randomized controlled trial to test a community-based integrated peer support and mHealth intervention to improve viral suppression among Hispanic and Black people living with HIV

BackgroundSignificant disparities continue to exist in the HIV care continuum, whereby Hispanic and Black people living with HIV (PLWH) are less likely to achieve viral suppression compared to their White counterparts. Studies have shown that intervention approaches that involve peer navigation may play an important role in supporting patients to stay engaged in HIV care. However, implementation may be challenging in real-world settings where there are limited resources to support peer navigators. Combining a peer navigation approach with scalable mobile health (mHealth) technology may improve impact and implementation outcomes.MethodsWe combined a peer navigation intervention with a mHealth application and are conducting a randomized controlled trial (RCT) to test the efficacy of this integrated “Peers plus mobile App for Treatment in HIV” (PATH) intervention to improve HIV care engagement, and ultimately sustained viral suppression, among Hispanic and Black PLWH. We will enroll up to 375 PLWH into a two-arm prospective RCT, conducting follow-up assessments every 3 months up to 12 months post-baseline. Participants randomized to the control arm will continue to receive usual care Ryan White Program case management services. Individuals randomized to receive the PATH intervention will receive usual care plus access to two main intervention components: (1) a peer navigation program and (2) a mHealth web application. The primary outcome is sustained HIV viral suppression (undetectable viral load observed at 6- and 12-month follow-up). Secondary outcomes are retention in HIV care, gaps in HIV medical visits, and self-reported ART adherence. Recruitment for the RCT began in November 2021 and will continue until June 2024. Follow-up assessments and medical chart abstractions will be conducted to collect measurements of outcome variables.DiscussionThe efficacy trial of PATH will help to fill gaps in our scientific understanding of how a combined peer navigation and mHealth approach may produce effects on HIV care outcomes while addressing potential implementation challenges of peer navigation in Ryan White-funded clinics.Trial registrationThe PATH trial is registered at the United States National Institutes of Health National Library of Medicine (ClinicalTrials.gov) under ID # NCT05427318. Registered on 22 June 2022.

Epidemiology of HIV infection and AIDS

Background: The expansion of antiretroviral therapy (ART) has resulted in a reduction in numbers of new human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS)-related deaths worldwide, except in some regions. As people with HIV live long and healthy lives, their health issues are also changing. In this review, we briefly summarize the global HIV epidemic and examine the changing trends in the epidemiology of HIV in Korea.Current Concepts: Since 2013, more than 1,000 new infections have been reported in Korea every year, and after reaching its peak at 1,223 in 2019, approximately 1,000 were reported each year during the coronavirus disease 2019 pandemic. Most newly infected people were men, and the proportion of young people aged 20 to 40 years, men who have sex with men, and foreigners has been steadily increasing. AIDS was the most common cause of death, and cancer, chronic diseases, and suicide were also important causes of death in Korea.Discussion and Conclusion: Achieving sustained ART and viral suppression is approaching the UNAIDS 95-95-95 targets in Korea, but additional research and efforts are required to reduce late presentation and scale-up of HIV diagnosis. Targeted and coordinated prevention programs to prevent HIV among people from key populations are also needed. Additionally, supportive services for older people with HIV, including cancer screening and chronic disease management, and multifaceted efforts to reduce stigma and discrimination against people with HIV are needed in Korea.

Factors associated with vertical transmission of HIV in the Western Cape, South Africa: a retrospective cohort analysis.

Monitoring mother-infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination. We used routinely collected data on infants with HIV exposure, born May 2018-April 2021 in the Western Cape, South Africa, with follow-up through mid-2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed-effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery. We included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non-nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was <100 copies/ml in 78% and CD4 count ≥350 cells/μl in 62%. HIV-PCR results were available for 86%, 67% and 48% of eligible infants at birth, 10 weeks and >14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL<100, 100-999, 1000-99,000 and ≥100,000 copies/ml nearest delivery, infant HIV diagnosis incidence was 0.4%, 2.3%, 6.6% and 18.4%, respectively. Increased VT was strongly associated with recent elevated maternal VL with a seven-fold increased rate with even modestly elevated VL (100-999 vs. <100 copies/ml). VT was also associated with unknown/low maternal CD4, maternal age <20 years, no antenatal ART, later maternal ART start/restart in pregnancy and ART gaps. Despite high maternal ART coverage and routine postnatal prophylaxis, ongoing VT remains a concern. Timing of infant HIV diagnoses suggests intrapartum and/or breastfeeding transmission in nearly 60%. Interventions to ensure retention on ART and sustained maternal viral suppression are needed to reduce VT.

Tailoring HIV Care for Black Populations: A Pilot Feasibility Prospective Cohort Study.

Research has shown that integrating community health workers (CHWs) into the formal health care system can improve outcomes for people living with HIV, yet there is limited literature exploring this framework among marginalized minority populations. Herein, we discuss the feasibility of a clinic-embedded CHW strategy to improve antiretroviral therapy adherence among Black people living with HIV in Miami-Dade County, Florida, a designated priority region for the US Department of Health and Human Services' Ending the HIV Epidemic Initiative. From December 2022 to September 2023, three CHWs were trained and integrated into the hospital workflow to provide support as members of the clinical team. Ten Black adults with an HIV viral load over 200 copies/mL were enrolled to received 3 months of CHW support focused on navigating the health system and addressing poor social determinants of health. Intervention feasibility was based on 4 criteria: recruitment rate, demographic composition, study fidelity, and qualitative feedback on CHW perceptions. Participants were recruited at a rate of 5.7 participants per month, with the sample evenly distributed between men and women. Retention was moderately strong, with 7 (70%) of the 10 participants attending more than 75% of CHW sessions. Qualitative feedback reflected CHW perceptions on clinical interactions and intervention length. Outcomes indicate that a clinic-integrated CHW approach is a feasible and acceptable methodology to address adverse social determinants and improve HIV treatment adherence. By offering targeted social and clinical support, CHWs may be a promising solution to achieve sustained viral suppression and care engagement for Black people living with HIV.

A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2mgkg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10mgkg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.

Explaining racial and ethnic disparities in antiretroviral therapy adherence and viral suppression among U.S. men who have sex with men.

To identify factors - including social determinants of health (SDOH) - that explain racial/ethnic disparities in antiretroviral therapy (ART) adherence and sustained viral suppression (SVS) among U.S. men who have sex with men (MSM) with HIV. We used weighted data from 2017-2021 cycles of the Medical Monitoring Project. Among MSM taking ART, we calculated prevalence differences (PDs) with 95% confidence intervals (CIs) of ART adherence (100% ART adherence, past 30 days) and SVS (all viral loads in past 12 months <200 copies/ml or undetectable) for Black MSM (BMSM) and Hispanic/Latino MSM (HMSM) compared with White MSM (WMSM). Using forward stepwise selection, we calculated adjusted PDs with 95% CIs to examine if controlling for selected variables reduced PDs. After adjusting for age, any unmet service need, federal poverty level (FPL), food insecurity, homelessness, time since HIV diagnosis, gap in health coverage, and education, the BMSM/WMSM PD for ART adherence reduced from -16.9 to -8.2 (51.5%). For SVS, the BMSM/WMSM PD reduced from -8.3 to -3.6 (56.6%) after adjusting for ART adherence, age, homelessness, food insecurity, gap in health coverage, FPL, any unmet service need, time since diagnosis, and ER visit(s). The HMSM/WMSM PD for ART adherence reduced from -9.3 to -2.9 (68.8%) after adjusting for age and FPL. The unadjusted HMSM/WMSM PD for SVS was not statistically significant. Adjusting for SDOH and other factors greatly reduced racial/ethnic disparities in ART adherence and SVS. Addressing these factors - particularly among BMSM - could substantially improve health equity among MSM with HIV.

FERROPTOSIS IN CD4+ AND CD8+ T-CELLS IN THE SETTINGS OF HIV INFECTION

Introduction: Elevation of intracellular iron concentration triggers ferroptosis. Understanding the regulation and pathophysiological mechanisms of this process in HIV infection may contribute to antiretroviral therapy (cART) monitoring. Aim: To perform a correlation analysis of the intracellular labile-bound iron pool (LIP) in CD4+ and CD8+ T cells in association with CD4+, CD8+ T cells absolute count (AC) and CD4/CD8 index in HIV+ individuals on continuous cART with sustained viral suppression. Material and methods: Peripheral blood samples (Li heparin, n=34) were collected in the course of the routine immune monitoring of HIV+ individuals at four time points during 24 months. Plasma HIV viral load (VL) was determined with the Abbott Real-Time HIV-1 test (sensitivity 40 copies/ml). AC and percentage of CD4+ and CD8+ T cells were determined by direct flow cytometry (Multitest, BD Trucount, FACS Canto II). The intracellular content of LIP in CD4 and CD8 T cells (LIP CD4, LIP CD8) was measured at the beginning of the study, using acetoxymethyl ester and subsequent incubation with a chelator (Deferiprone). LIP was quantified according to the mean fluorescence intensity (MFI) (FACSCanto II, Diva 6.1.2). Results: In the settings of a higher LIP CD4 , high LIP CD8 correlated with increased CD8AC (Rho=0.70, p&lt;0.05) up to 11 (min. 6, max. 15) months after LIP measurement., and decreased CD4/CD8 ratio correlated inversely with LIP CD8 in all consecutive measurements (Rho= -0.71, p&lt;0.01 for all), Importantly, high LIP CD8 correlated with a lower CD4AC (Rho=-0.65, p&lt;0.05) up to five (min.1, max.8) months after LIP measurement. Conclusion: The increased concentration of intracellular LIP in CD8 cells in HIV+cART individuals could indicate viral activity in the settings of undetectable HIV VL, directly associated with ongoing cell ferroptosis.

CD4+ T-cell recovery in HIV/hepatitis C co-infected patients following successful hepatitis C treatment.

Hepatitis C virus (HCV)/HIV co-infection has been identified as a risk for impaired CD4+ T-cell recovery, possibly mediated by HCV-induced liver fibrosis and/or immune activation. As HCV direct-acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA-induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non-responders [INRs]). Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre-DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre-DAA period (-36 months) versus the post-DAA period (+36 months). In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6-month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6-month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6-month time interval [p = 0.02]). In total, 54% of INRs recorded a post-DAA CD4 count of >350 cells/mm3. Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery.

Social Determinants of Health Among Persons Living with HIV Impact Important Health Outcomes in Michigan.

Addressing social determinants of health (SDOH) is a national priority for improving quality of life and addressing obstacles to accessing care for people living with HIV (PLWH). Utilizing the Oregon Social Determinants of HIV Health Index and CDC's Medical Monitoring Project, we examined the association between social determinants of health and various HIV clinical outcomes and quality of life indicators, including stigma and mental health, for people living with HIV in Michigan. We calculated estimates of SDOHs, clinical outcomes, stigma, and mental health using weighted percentages and prevalence ratios with predicted marginal means, adjusting for age, race/ethnicity, and gender/sexual orientation. Compared with PLWH reporting 0-1 SDOH challenges, those reporting ≥ 4 SDOH challenges were more likely to miss ≥ 1 HIV care appointment (aPR: 2.57, 95% CI 1.70-3.88), have symptoms of depression (aPR: 4.03, 95% CI 2.68-6.05) and anxiety (aPR: 3.55, 95% CI 2.25-5.61), and less likely to have 100% antiretroviral therapy (ART) adherence (aPR: 0.62, 95% CI 0.50-0.78) and sustained viral suppression (aPR: 0.77, 95% CI 0.65-0.90). Stigma scores were highest for those reporting ≥ 4 SDOH challenges. Our findings indicate significant associations between SDOH and adverse HIV health and quality of life outcomes which can inform and direct federal, state, and local strategies aimed at improving these outcomes. Linking PLWH to social support services and providing mental health screening and care services could benefit their mental and emotional well-being, leading to better healthcare outcomes.

Investigating the Relationship between Medication Adherence Behaviors and the Achievement of Sustained Viral Load Suppression among People Living with HIV (PLHIV) on Antiretroviral Therapy (ART) in Akwa Ibom State, from 2018 - 2022

Background: Nigeria is still endemic for Human Immuno-Deficiency Virus (HIV), and currently among the top five countries with the highest burdens of HIV infection. For a successful HIV program, there should be good access to antiretroviral therapy (ART) and record of viral load suppression (VLS). This study aimed at investigating the relationship between medication adherence behavior (MAB) and sustained VLS among people living with HIV (PLHIV) receiving ART in Akwa Ibom State. Methods: This was a retrospective cohort study of the medical records of 1,763 PLHIV receiving ART services from January 2018 to December 2022, in selected ten health facilities in Akwa Ibom State. Relevant demographic, clinical, immunological, viral load (VL) information were obtained from the patients’ medical records and databases. The proportion of VLS and associated variables were then analyzed. Results: Out of the 2,550 PLHIV whose medical records were accessed, data for 1,763 PLHIV was accepted for analysis. A total of 795 (45.1%) male and 968 (54.9%) female participated in the study, with a mean age of 38.4 ± 5 years. While 23.8% (n = 420) have unsuppressed VL of &gt;1,000 copies/mL; 76.2% (n = 1,343) of participants achieved VLS of &lt;1,000 copies/mL. 90.4% (n = 1,213) of the virally suppressed participants recorded moderate to high medication adherence levels (X2 = 94.977, df = 2, p-value = 2.2 x 10-16). CD4 counts and HAART regimen have significant impact on VLS (p &lt; 0.05), while pregnancy status, TB Infection, duration on HAART, and WHO disease stage do not have significant effects on VLS (p &gt; 0.05). Conclusion: There was a strong evidence to reject the null hypothesis, which states that there is no positive association between MAB and sustained VLS among PLHIV on ART (p &lt; 0.05). The VLS rate in this study indicates a good HIV epidemic control. Good medication adherence level, high baseline CD4 count, and being on first line HAART regimen were strongly associated with VLS.

1612. Correlates of Sustained Viral Suppression among HIV-Positive Adults Receiving Antiretroviral Therapy from Six Secondary Health Facilities in Northern Nigeria.

Abstract Background Sustained viral suppression in HIV is essential to minimize drug resistance, reduce secondary transmission and improve health outcomes necessary to achieve the UNAIDS 95-95-95 strategy. There is dearth of information on viral suppression among adults in Nigeria. Identifying correlates of sustained viral suppression will inform treatment guidelines especially for people at risk and provide recommendations to policy makers. Methods We collected sociodemographic and HIV-related data from a cross-section of 730 HIV-positive adults receiving antiretroviral therapy from six secondary health facilities in northern Nigeria, between October 2021 and February 2022. Sustained viral suppression was defined according to the Nigerian National Guideline for HIV Prevention, Treatment and Care as a viral load below the detection threshold of less than 20 copies of HIV RNA/ml. Proportion of participants with sustained viral suppression was estimated and a multivariable analysis used to identify independent correlates of sustained viral suppression. Results The sustained viral suppression rate among HIV-positive adults on ART was 35.7% [95% CI: 32.2, 39.5]. Being married [AOR 2.01; 95% CI: 1.34, 3.03] and having secondary education [AOR 0.43; 95% CI: 0.26, 0.74] were significantly associated with sustained viral suppression. Respondents on treatment for 5-10 years [AOR 1.76; 95% CI: 1.17, 2.64] and those taking two or more pills [AOR 5.67; 95% CI: 3.74, 8.62] were more likely to have sustained viral suppression. Previous treatment for opportunistic infection [AOR 0.24; 95% CI: 0.15, 0.41] significantly decreased the likelihood of sustained viral suppression. Conclusion Sustained viral suppression rates among HIV-positive adults on ART in the six facilities were suboptimal. While being married, taking two or more ART pills and being on treatment for 5-10 years increased the likelihood of having a suppressed viral load, being educated up to secondary level and previous treatment for opportunistic infection decreased the odds of having sustained viral suppression. There is a need to improve viral load monitoring and direct viral suppression interventions towards at risk population. Disclosures All Authors: No reported disclosures

Impact of point-of-care HIV viral load and targeted drug resistance mutation testing on viral suppression among Kenyan pregnant and postpartum women: results from a prospective cohort study (Opt4Mamas).

Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized laboratory systems faces many barriers. We aimed to determine the impact of point-of-care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy. We conducted a pre/post-intervention prospective cohort study among 820 pregnant women accessing HIV care at five public-sector facilities in western Kenya from 2019 to 2022. The pre-intervention or "control" group consisted of standard-of-care (SOC) centralized VL testing every 6 months and the post-intervention or "intervention" group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS. At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS (aRR 1.00, 95% confidence interval [CI] 0.98, 1.02). When assessing VS using a threshold of <40 copies/ml, VS proportions were lower overall (90-91%) but remained similar between groups. Among women with viraemia (VL>1000 copies/ml) who underwent successful DRM testing in the intervention group, all (46/46, 100%) had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day (IQR 1, 4) for POC VL in the intervention group and 7 days (IQR 5, 9) for SOC VL in the control group. Sustained VS throughout follow-up was similar between groups with either POC or SOC VL testing (90-91% for <1000 copies/ml, 62-70% for <40 copies/ml). Our combined strategy markedly decreased turnaround time but did not increase VS rates, which were already very high, or sustained VS among pregnant and postpartum women living with HIV. Further research on how best to utilize POC VL and DRM testing is needed to optimize sustained VS among this population.