Antiretroviral Research Articles

Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease

AbstractDespite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Defining Appropriate Comparator Populations for Placental Pathology for Pregnant People With HIV

Background. Widespread adoption of antiretroviral therapy has reduced perinatal transmission of HIV; however, people living with HIV (PWH) have higher rates of preterm birth and hypertensive disorders of pregnancy. The placenta is the critical fetal support organ in pregnancy, and multiple investigations have sought associations in PWH between HIV and placental pathology. However, results have been inconclusive. We posit that selection of control group populations influences the apparent anomalies in placentas from PWH and examined the differences seen between these placentas and those of four comparator populations. Methods. Placentas from PWH were compared with those from all patients without HIV, controls from a recent study of severe acute respiratory syndrome coronavirus 2 in pregnancy, patients with a history of melanoma—an indication for examination relatively orthogonal to other problems in pregnancy, and patients paired with PWH using propensity score matching. Results. People living with HIV differ in demographics and comorbidities from comparator groups other than propensity score–matched patients. Placentas from PWH had higher rates of acute placental inflammation, including maternal inflammatory response and fetal inflammatory response, than multiple comparator groups. Placentas from PHW had lower rates of chronic placental inflammation than three of four comparator groups, including the largest comparator group and the group matched to PWH using propensity scores. Conclusion. Differences in placental pathology in PWH depend on the comparator group. Commonly used comparator groups have significantly different demographic and comorbidity profiles, suggesting they are inappropriate comparators for PWH. Propensity score matching may be useful in identifying comparator populations.

Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy

Abstract Objective Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes. Methods Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA. Results Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF. Conclusions Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.

Pretreatment and acquired HIV drug resistance in Belize—results of nationally representative surveys, 2021–22

Abstract Background The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. Objectives To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. Patients and methods Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. Results The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%–56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71–18.95; P = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02–9.34; P < 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. Conclusions Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR.

Dissecting the Role of Donors in Capacity Building for HIV/AIDS Treatment, Care and Support: A Case Study of an Antiretroviral Therapy Programme in Zimbabwe

Donor involvement in development activities in the Global South has been questioned for failing to capacitate communities in the recipient country. Therefore, the need to establish whether the Médecins Sans Frontières (MSF) antiretroviral treatment (ART) programme in Zimbabwe contributed to capacity building for HIV and AIDS support, care and treatment triggered this study. A qualitative methodology involving semi-structured interviews with purposively selected participants was adopted. As a result of the MSF programme, community-based clinics created ART support groups which facilitated easy access to medication and health-related information. Dispensing of medication and testing could also be done in these clinics, which were previously the district hospitals. These interventions reduced waiting periods and long-distance travel to access HIV and AIDS care, support and treatment, thus improving the healthcare quality. Community-influenced strategies are recommended to sustain these improvements.

IMPLANTES DENTÁRIOS INSTALADOS EM PACIENTES PORTADORES DO VIRUS DA IMUNODEFICIENCIA HUMANA (HIV)

The Human Immunodeficiency Virus (HIV) compromises the immune system and, as it progresses, causes acquired immunodeficiency syndrome (AIDS), characterized by the emergence of opportunistic infections. Transmission occurs mainly through sexual contact or via blood and, in Brazil, between 1980 and 2022, more than 1 million cases of AIDS were recorded. Regarding implantology, patients with HIV face oral complications such as gingivitis and candidiasis, and although the impact of osseointegrated implants in these patients is not yet entirely clear, prior evaluation of bone health and conditions is essential. This research aims to describe the care in the osseointegration process in HIV-positive patients, investigating the possible complications and the importance of biosafety, in addition to highlighting the relevance of treatment to improve the quality of life of these patients. The methodology used was the bibliographic review, using articles published between 2012 and 2022 in Portuguese. Oral rehabilitation with dental implants in HIV-positive patients has gained importance due to the increase in life expectancy provided by antiretroviral therapy. These patients, with an improved quality of life, are looking for viable options to replace missing teeth, with dental implants being an attractive alternative. Although the literature on the topic is limited, the results indicate that the success rates of implants in patients with HIV are similar to those of healthy patients, as long as the treatment considers the immune status. However, specific care is needed, such as monitoring for possible complications resulting from the continuous use of antiretrovirals, which can cause liver and kidney problems. Additionally, strict biosafety protocols are essential to ensure the safety of patients and healthcare providers. Further research is recommended to clarify outstanding issues and improve pre- and postoperative care, providing more predictable outcomes and greater safety in treatment with osseointegrated implants.

Feasibility and Impact of Community Pharmacy and Novel Pick-up Points for Antiretroviral Therapy Pre-exposure Prophylaxis Initiation and Continuation in Low and Middle-income Countries.

This review assesses recent developments in community access to pre-exposure prophylaxis (PrEP) for HIV prevention in low-and middle-income countries (LMICs). It examines literature on differentiated service delivery (DSD) and alternative delivery modes for PrEP, focusing on the role of community pharmacies and novel pick-up points. Key considerations include barriers to access, potential benefits, and strategies for implementation. Challenges to optimal HIV healthcare delivery persist globally, with LMICs facing greater barriers due to resource constraints and structural obstacles. Community pharmacies and novel pick-up points offer promising avenues to expand access to HIV medication, especially in hard-to-reach populations. However, operational complexities and regulatory frameworks present significant challenges. Recent initiatives, such as collaborative practice agreements and programmes by global health agencies, highlight efforts to integrate community pharmacies into HIV prevention and care delivery. Mobile health clinics and home delivery services have also shown promise in improving treatment coverage. Community pharmacies and novel pick-up points play a crucial role in enhancing access to HIV PrEP in LMICs. Despite challenges related to infrastructure, funding, and regulatory oversight, innovative strategies like DSD and mobile outreach offer opportunities to reach marginalized populations. Real-life examples from LMICs demonstrate the feasibility and effectiveness of leveraging community pharmacies for HIV treatment. However, addressing policy gaps, strengthening pharmacist training, and promoting patient-centred approaches are essential for scaling up access to PrEP. Collaboration between governments, health agencies, and local communities is key to realizing the full potential of community pharmacies in HIV prevention and care.

Impact of Expanded HIV Testing and Rapid Antiretroviral Therapy Initiation in Southwest China: An Interrupted Time-Series Analysis.

This study evaluates the impact of an expanded HIV testing initiative, launched in June 2018 in Luzhou, Sichuan, China, on antiretroviral therapy (ART) initiation rates among people living with HIV (PLWH). Using an uncontrolled interrupted time-series design, we analyzed data from 11,040 PLWH between June 2016 and December 2022, extracted from 108 health facilities via the Center for Disease Control and Prevention's ART database. The primary outcome measures were ART initiation rates within 7 and 30 days of HIV diagnosis. Results showed a significant improvement in the 30-day ART initiation rate following expanded testing, increasing from 46.1% to 90.9% by the study's end. The 7-day initiation rate also improved but remained below 30%. The study found that expanded testing enhanced the role of primary health care institutions in ART initiation. However, the COVID-19 pandemic, beginning January 2020, negatively impacted ART initiation rates, with a slight effect on 30-day rates but a persistent negative impact on 7-day rates. Despite these challenges and an increased HIV burden, Luzhou's ART initiation rates surpassed the national average. This study emphasizes the effectiveness of expanded HIV testing in ensuring timely ART access, crucial for HIV epidemic control, and improved patient outcomes. It also reveals challenges in maintaining HIV services during public health crises, offering insights into health care system resilience. Future research should focus on evaluating long-term treatment outcomes and strategies to support ending the AIDS epidemic.

Factors associated with High Viral Loads among HIV Patients Under ARV at Gitwe District Hospital

Background: High viral load is a condition of rapid multiplication in blood stream. The high viral load among HIV patients under ARV may also occur due to the rapid multiplication of virus leading to compromise immune system of living organism up to death. The vast majority of people living with HIV virus face with persistent of high viral load while were under treatments (ARV). Aim: The aim of the study was to evaluate and assess the factors associated with high viral load among HIV patients under ARV at Gitwe District Hospital. Methodology: The retrospective study was conducted to assess high viral load of HIV patients under ARV. The only significance factor for viral load were adherence with (p=0.000173) and ages with (p=0.00023). Results and conclusion: A large of number of PLWH were highly VL tested, and 95 subjects were recorded for study. Among 95 subjects, 54.73% were female and 45.26% male. All data were analyzed using statistical package for social science (SPSS) version 20. The results have showed provider’s advices and ART use, adherence counselling. Keywords: High viral load, HIV, Antiretroviral therapy, Gitwe District Hospital.

In vitro and patient studies with platelets to explore off-target cardiovascular effects of integrase inhibitors.

People with HIV currently face a tenfold higher risk of developing cardiovascular disease (CVD) than those without HIV. Studies have shown various off-target effects of antiretroviral treatment (ART) on the cardiovascular system, but little is known about the effects of currently used integrase strand transfer inhibitors (INSTIs) on platelets. Platelet activation is associated with increased CVD, thrombus formation, and release of proinflammatory mediators, so exploring platelet effects from currently prescribed ART may contribute to the understanding of CVD etiopathogenesis in people with HIV. We aimed to identify potential effects of INSTIs on platelet aggregation and activation markers from individuals without HIV after in vitro treatment with clinically relevant drug concentrations. We used bictegravir (BIC) and dolutegravir (DTG) individually or in the therapeutic drug combinations BIC/emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) or DTG/lamivudine (3TC). Additionally, we conducted a pilot study to compare platelet activity profiles from people with HIV on BIC/FTC/TAF and DTG/3TC. Changes to in vitro platelet aggregation responses upon exposure to different INSTIs were observed both upon individual drug application and when using therapeutic combinations. However, these effects were not reflected in flow-cytometric evaluation of platelet degranulation. A pilot study in eight people with HIV and eight without HIV revealed no significant effects but established protocols for future patient studies. There is currently no consistent evidence of an effect of INSTIs on platelet activation. Further study is warranted, focusing on models with more pathophysiological relevance, including extensive studies in people with HIV.

Life Course Stressors, Latent Coping Strategies, Alcohol Use, and Latent Coping Strategies Among People with HIV.

People with HIV (PWH) have often experienced chronic stressors across their lifespan, including adverse childhood experiences (ACES), lifetime economic hardship (LEH), and concurrent stressors associated with living in urban areas (urban stress). Prolonged exposure to stressors might result in differential coping patterns among PWH that can impact care trajectories. We utilized a life course-informed approach to examine chronic stressors as antecedents of latent coping strategies among PWH in care. High-risk alcohol use and non-adherence to anti-retroviral therapy (ART) were examined as consequences of latent coping strategies. Data were utilized from the baseline and interim follow-up visit of the New Orleans Alcohol Use in HIV (NOAH) study. Three latent classes of coping strategies were identified: avoidance coping (31%), low-frequency coping (43%), and problem-solving coping (25%). Exposure to ACES was associated with greater use of avoidance versus low-frequency coping class at wave II. Urban stress was associated with greater use of avoidance coping compared to problem-solving or low-frequency coping classes at wave II. LEH was associated with greater use of low-frequency coping at wave II. Those utilizing low-frequency coping had a two-fold increase in ART non-adherence compared to problem-solving coping. PWH utilizing avoidance and low-frequency coping had a nearly two-fold increase in high-risk alcohol use versus problem-solving coping. These findings reveal important coping classifications that are linked to stressors across the life course of PWH. An understanding of coping styles and stressors may aid in improving the continuum of care among PWH by reducing alcohol use and improving medication adherence.

Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks.

Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH. We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW. Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%-22% and <11%-120%, respectively). If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.

Profound reduction of HIV-1 reservoir cells over three decades of antiretroviral therapy started in early infancy.

HIV-1 reservoir cells persist indefinitely during suppressive antiretroviral therapy (ART) in individuals who acquire infection in adulthood, but little is known about the longitudinal evolution of viral reservoir cells during long-term ART started during early infancy. We studied two fraternal twins who acquired HIV-1 perinatally, started ART at week 10 after birth and remained on ART for 28 years. We observed that the frequency of genome intact proviruses, determined by single-genome near full-length proviral sequencing, declined by approximately 4,000- to 13,000-fold during this period, indicating enhanced decay rates of intact proviruses even after adjusting for dilution effects from somatic growth. Despite analyzing more than one billion PBMC after 28 years of ART in each participant, no intact proviruses were detected in one participant, and one intact provirus was isolated in the other. The longitudinal decline of defective proviruses in the two participants was more similar to proviral decay kinetics reported in individuals who started ART during adulthood; moreover, clonal sequence clusters were readily detectable for defective proviruses but not for intact proviruses after 28 years of ART in the two twins. Together, these data suggest decreased long-term stability and increased immunological vulnerability of intact proviruses during long-term ART started in early infancy.

The Impact of Undernutrition and Anemia on HIV-Related Mortality Among Children on ART in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Although there have been significant advancements in providing HIV-infected children with access to antiretroviral therapy (ART), the mortality rates have remained unacceptably high. Inadequate nutrient intake or absorption is a widespread problem in several African nations, resulting in undernutrition and anemia. However, the pooled effect of malnutrition and anemia on HIV-related death related to children receiving ART was not investigated in sub-Saharan Africa. We searched multiple electronic databases (PubMed/MEDLINE, Embase, CINAHL, and Web of Science) for observational studies published between January 1, 2010, and April 24, 2024 that reported the risk factors or effects of undernutrition and, anemia on HIV-related mortality among children. Study selection, data extraction, and quality evaluation were carried out separately by two reviewers. A meta-analysis was conducted using random effect models. The review included 27 studies with a combined total of 61,796 study participants. The study findings showed that severe wasting (HR: 2.49; 95% CI: 1.87-3.30), being underweight (HR: 2.11; 95% CI: 1.64-2.72), and Anemia (HR: 2.58; 95% CI: 2.08-3.19) were highly linked to HIV-related death among children. The risk of death due to anemia was greater among children under the age of 5 years than older children. Undernutrition and anemia in sub-Saharan African children increased the risk of HIV-related death. The impact of malnutrition and anemia among under 5 years old children with HIV/AIDS was more pronounced, suggesting that these conditions at this early age can have more serious consequences for a child's survival. The importance of combining nutrition with HIV treatment programs in sub-Saharan African countries is crucial.

Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV, Part II: Drugs Licensed Before 2005.

Advances in antiretroviral therapy led to an increase in life expectancy among people living with human immunodeficiency virus (HIV). As aging is characterized by several physiological changes that can influence pharmacokinetics (PK), this systematic review aims to describe the impact of aging on the PK of antiretrovirals (ARV) approved by the Food and Drug Administration (FDA) before 2005. Searches were performed in BVS, EMBASE, and PubMed databases for publications until June 2024. Peer-reviewed published studies were included if they met the following criteria: adults (≥ 18 years) living with HIV; reporting at least one PK parameter or plasma concentration of any ARV approved by the US FDA before 2005 and still used in the clinic: lamivudine (3TC), emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), abacavir (ABC), zidovudine (ZDV), efavirenz (EFV), nevirapine (NVP), atazanavir (ATV), lopinavir (LPV), ritonavir (RTV), tipranavir (TPV), and fosamprenavir (FPV); PK parameters stratified per age group as young (aged 18-49 years) or older (age ≥ 50 years) adults; and manuscripts published in English, Portuguese, or Spanish. All studies were evaluated for risk of bias. The review protocol was registered in the PROSPERO database (registration no. CRD42023463092). Among 106 studies included, only 22 evaluated the PK of participants aged 50 years or older and only 5 studies compared the PK between young and older adults for ATV, RTV, EFV, and 3TC. Our analysis revealed an increase in minimal concentration (Cmin) values for LPV, RTV, and ATV in older adults. While increased values of the area under the curve (AUC) and maximum concentration (Cmax) were observed in older adults using ATV, 3TC, and FTC, no differences in PK were apparent between young and older adults for ABC and EFV, with no estimation possible for ZDV. Exposure to 3TC, TDF, FTC, ATV, LPV, and RTV increases with age, while exposure to ABC and EFV appears to be unaffected. Despite the large quantity of data on PK in young adults, there is still a gap in knowledge about the effects of aging on the PK of these ARVs.

2024 American Heart Association and American Red Cross Guidelines for First Aid.

Codeveloped by the American Heart Association and the American Red Cross, these guidelines represent the first comprehensive update of first aid treatment recommendations since 2010. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines cover first aid treatment for critical and common medical, traumatic, environmental, and toxicological conditions. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include opioid overdose, bleeding control, open chest wounds, spinal motion restriction, hypothermia, frostbite, presyncope, anaphylaxis, snakebite, oxygen administration, and the use of pulse oximetry in first aid, with the inclusion of pediatric-specific guidance as warranted.

Antiviral therapy for cytomegalovirus retinitis: A systematic review and meta-analysis.

Cytomegalovirus retinitis (CMVR) is a significant cause of blindness in patients with advanced acquired immunodeficiency syndrome (AIDS). There are no established guidelines for its treatment, resulting in varied antiviral approaches. We pooled data from 59 studies (4,501 patients) to evaluate treatment variations and outcomes (CRD42022321088). Overall pooled estimates showed visual acuity improvement at 18% (95% CI: 7-41%), inflammation resolution at 90% (95% CI: 81-95%), retinal detachment at 11% (95% CI: 8-14%), and recurrence at 19% (95% CI: 11-31%). The main antiviral treatment approaches identified were: (1) intravenous antivirals alone in 33 studies, (2) intravitreal antivirals alone in 26 studies, (3) oral antivirals alone in 3 studies, and (4) a combination of systemic (oral or intravenous[IV]) and intravitreal antivirals in 7 studies, with varying schemes and durations. Ganciclovir was the predominant antiviral, with intravenous administration being the most reported (in 23 studies), followed by intravitreal administration (in 20 studies). While visual acuity improvement was comparable, inflammation resolution tended to be higher with intravitreal than with IV antivirals, though not statistically significant (88%, 95% CI: 69-96% vs 75%, 95% CI: 35-94%, p = 0.38). Retinitis progression rate for IV ganciclovir was lower than for those without ganciclovir. Inflammation recurrence was significantly lower in antiretroviral (ART)-treated compared to non-ART-treated HIV/AIDS patients (10% (95% CI: 4-20%) vs 33% (95% CI: 19-50%), p < 0.01). Neutropenia, particularly with ganciclovir, was the most reported adverse effect (up to 50%).

Incentive based continuum of care for people living with HIV including orphan vulnerable children- the Delhi Model

Background: Delhi State AIDS Control Society (DSACS) addressed critical integration of services for Orphan and Vulnerable Children (OVC) in context of HIV. They bridged the policy and implementation divide by formulating a multisectoral-strategy in April 2012, creating a model of "Continuum-of-Care for People-Living with HIV (PLHIV), OVC &amp; Children-Affected-by-HIV (ChABH)” in Delhi. With input from the National Commission for Protection of Child Rights, DSACS sensitized political and administrative machinery about needs and challenges related to HIV/AIDS. DSACS developed an incentive-based system for Antiretroviral Therapy (ART) adherence, incorporating safeguards and robust monitoring. Delhi Government's sustained financial commitment and DSACS programmatic-innovation provide a scalable blueprint for India and global initiatives. Description: This ongoing Delhi Government's scheme focuses on household-economic-strengthening of PLHIV as an incentive for broader behaviour change based-on specific eligibility conditions. Beneficiaries fall into four categories: PLHIV, including children on ART; double orphan HIV positive children (OCI); destitute children living with HIV/in institutional care (DCI); and double orphan ChABH in community-based care in Delhi. Category-wise fixed-monthly financial assistance is released to beneficiaries via direct-bank-transfers leveraging Aadhaar-platform to eliminate corruption. Adherence to treatment is mandatory to continue cash-transfers. Linkages with other schemes established to maximize impact. Lessons learned: In its 11-year evolution, Delhi model has grown from 1110 to 6467 beneficiaries, including 6383 PLHIV, 34 double OCI, 50 DCI, and 27 double orphan ChABH, with 5875 (90.8%) currently active excluding beneficiaries who expired (n=328), migrated/ transferred out of Delhi (n=115), opted-out ART/or lost-to-follow-up (n=135), and 14 CABA who turned major. Steady progress and 98% ART adherence mark positive outcomes. DSACS eased eligibility criteria in 2018, facilitating hurdle-free enrollment, while responding to cost-inflation by enhancing financial assistance, showcasing program adaptability. Achieving &gt;95% ART adherence has significantly boosted survival rates, underscoring program's positive impact on beneficiary health. The scheme's INR 14,69,35,600 expenditure in 2022-23, just 0.13% of Delhi Health Department's plan-outlay, signals a cost-effective investment. Extrapolating this nationally would represent 1.5% of India's Health Ministry's current plan-outlay. Conclusion/next steps: This innovative model is implementable on large-scale in India and around the globe but requires not only financial commitment but also coordinated efforts, policy adjustments, and collaboration between various stakeholders.

The incidence of symptomatic CSF viral escape in patients on antiretroviral therapy in western India: a retrospective cohort study.

Antiretroviral treatment (ART) effectively suppresses viral loads in both plasma and cerebrospinal fluid (CSF). Patients with discordant plasma and CSF viral loads may experience chronic-progressive or fluctuating neurocognitive dysfunctions. This study examined the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving ART. This retrospective cohort study was conducted between 2000 and 2023. The primary outcome measure was the incidence of symptomatic CSFVE. Nonparametric Mann-Whitney U and Fisher exact/χ 2 tests were applied for continuous and categorical variables, respectively. The cumulative incidence function with Gray's test was used to compare the incidence of CSFVE across the treatment regimens. During the study period, 52 of the 8415 patients were diagnosed with CSFVE. The median duration of HIV diagnosis in patients with CSF VE was 150 (12-288) months, with a median nadir CD4 + T-cell count 96.5 (13-601 cells/L)], and 75% of the patients were on a ritonavir-boosted protease inhibitor (PI/r) regimen. The cumulative incidence of symptomatic CSFVE at a follow-up of 14 years was 1% (95% CI, 0-1%). PI/r (HR 34.73; 95% CI 13.5 to 89.4; p < 0.001) and integrase strand transfer inhibitor (INSTI) (HR 3.42; 95% CI 1.94 to 6.02; p < 0.001) regimens were significantly more likely to be associated with CSFVE than the Non-nucleoside reverse transcriptase inhibitors (NNRTIs) regimens. NNRTIs had the lowest risk of CSFVE compared to the PI/r and INSTI regimens. A rapid and complete recovery is possible with symptomatic CSFVE if it is diagnosed and treated early.

Implementation of a Screening Program for High-Grade Anal Dysplasia in High-Risk Patients in a Tertiary Cancer Center.

The incidence of anal squamous cell carcinoma (SCC) has been increasing over the last decades. Human papillomavirus (HPV) infection accounts for more than 90% of anal cancers, and HIV co-infection increases the risk of invasive cancer. Men who have sex with men (MSM) with HIV are the highest risk group for developing anal high-grade squamous intraepithelial lesions (aHSILs), which can be found in 45%-50% of these patients and are precursor lesions for invasive cancer. Anal cytology is an effective screening tool, but it lacks sensitivity. High-resolution anoscopy (HRA) is the gold standard procedure for diagnosis and treatment of aHSILs. Recent data suggest that early detection and treatment of aHSILs could prevent the development of invasive cancer in this population. The objective of the study was to describe the implementation of an office-based screening program for anal cancer prevention in a Comprehensive Cancer Center in Brazil. Training included participation in the International Anal Neoplasia Society (IANS) HRA course at UCSF Medical Center Mount Zion in San Francisco, CA, USA, by three colorectal cancer surgeons. In-person and hands-on training was provided by a specialist through the AIDS Malignancy Consortium (AMC) of the US NIH. Equipment purchased and provided by the AMC included a colposcope with a digital camera, a hands-free mouse pedal, and a photo documentation imaging software program that allows images to be recorded for documentation and training purposes. The program was implemented in 2022 after a delay of more than two years due to the COVID-19 pandemic. An average of 24 exams are performed monthly. Patients with HIV aged 35 years or older who are undergoing antiretroviral therapy were recruited from the metropolitan area of Rio de Janeiro and referred by primary care providers for screening. Patients diagnosed with aHSILs are scheduled for in-office ablative treatment in the clinic. From March 2022 to June 2024, 324 exams were performed, and aHSIL was found in 38.2% of 220 high-risk patients, including 45 of 129 MSMs (34.9%), 6 of 19 transgender women (31.6%), and 33 of 72 women living with HIV (45.8%). A total of 69 treatments for aHSIL were performed in 62 patients. Patients are followed on a regular basis and long-term results are awaited, including the effectiveness of local therapy for aHSIL. The screening and treatment program was successfully implemented in a tertiary comprehensive Cancer Center. Team training and external proctorship were decisive for the achievement of benchmark standards. The program aims to permanently provide screening for the prevention of anal cancer through the detection and treatment of aHSIL within the National Cancer Institute of Brazil for populations considered at-risk for anal cancer.