HIV Treatment Strategies Research Articles

P-483. Late presentation of People Living With HIV in “Treat All” Era in Maputo City, Mozambique

Abstract Background Advanced HIV disease (AHD), defined as People Living with HIV with a CD4 cell count < 200 cells/mm3 or WHO clinical stage 3 or 4, increases the risk of severe opportunistic infections, hospitalizations, and death. Programmatic data from Mozambique showed a reduction in the prevalence of AHD at ART initiation from 73% to 37% during 2004-2014. Since 2016, Mozambique has adopted the “Treat all” strategy, and data on AHD at presentation for care is limited. We assess the prevalence of AHD in recently diagnosed HIV clients ART naïve. Relation between Age and Gender and AHD prevalece Methods An analysis of baseline data of a prospective cohort study in newly HIV-diagnosed ART naïve at Mavalane Health Centre (MHC) located in a periurban area in Maputo City. April 2021-November 2022, all HIV-1 diagnosed ART naïve above 18 years of age were enrolled. A questionnaire was administered to assess risk factors for HIV infection, and CD4+ T cell counts and HIV viral load were determined. Results A total of 1,025 PLHIV were enrolled, of whom 560 (55%) were females, median age of 35 (IQR: 30, 43) years, and mean BMI was 23.7 kg/m2 (SD: 4.48) with 8.1% under 18.5 kg/m2. The overall median CD4 + cell count was 252 (IQR: 140, 421) cells/mm3, with 46.0% (214/465, 95%CI: 41.4-50.7%) and 32.7% (183/560, 95%CI: 28.8-36.7%) of males and females, respectively, below 200 cells/mm3. There was an age-ascending trend (p-value: < 0.001) among females from 15.0% (95%CI: 8.6-23.5%) to 53.7% (95%CI: 43.2-64.0%). There was age dependency among males (p-value: 0.1887). The overall median log10 HIV-RNA was 5.12 (IQR: 4.67, 5.52), 4.41 (IQR: 3.63, 4.94) among AHD and non-AHD, respectively (p-value < 0.001). Conclusion This study unveiled a high burden of AHD, showing that even in an era when countries are working on strategies for early HIV diagnosis and treatment to reduce the incidence of HIV and mortality associated with opportunistic infections, clients are still presenting in an advanced stage of the disease. Disclosures All Authors: No reported disclosures

Effectiveness and Tolerability of DOR/3TC/TDF in Experienced People with HIV Switching from RPV/FTC/TDF: A Retrospective, Single Center Cohort Study.

Background: With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV (PLWH). Methods: this Italian retrospective study included 426 PLWH who switched from rilpivirine (RPV)/TDF/emtricitabine (FTC) to DOR/3TC/TDF. The analysis focused on treatment effectiveness, safety, and metabolic and renal markers. Results: this study reports a treatment failure (defined as virological failure or discontinuation of the regimen) rate of 2.34% (95% confidence interval, 1.28-4.50%), with significant improvement in CD4 counts (+49.93 cells/µL, p < 0.001). Notably, the switch to DOR/3TC/TDF did not result in adverse metabolic effects or significant changes in renal function. Analysis of lipid profiles showed stabilization in the majority of PLWH. Conclusions: this study indicates that switching to a DOR/3TC/TDF from RPV/TDF/FTC is an effective and well-tolerated option for PLWH, with benefits in terms of maintaining viral suppression, CD4 count recovery, and metabolic health, without evidence of renal impairment. These results support the continued use of DOR/3TC/TDF as part of HIV treatment strategies and highlight the need for ongoing research to refine ART regimens for different populations.

HIV treatment satisfaction: HIVTSQ-12 factor analysis and associated factors in Türkiye

BackgroundDespite global efforts, HIV/AIDS remains a significant public health challenge, with Türkiye witnessing a consistent rise in annual diagnoses. Patient satisfaction with antiretroviral therapy (ART) is crucial for treatment adherence and effectiveness. This study examines treatment satisfaction levels among people living with HIV (PLWH) in Türkiye and identifies associated factors.Materials and methodsA cross-sectional prospective cohort study was conducted at Tepecik Training and Research Hospital, Izmir, Türkiye, involving 238-PLWH receiving ART. Data were collected through face-to-face interviews using the HIV Treatment Satisfaction Questionnaire (HIVTSQ-12) and demographic/clinical forms. Confirmatory Factor Analysis and descriptive statistics were employed for data analysis.ResultsParticipants exhibited high overall treatment satisfaction, with significant associations between satisfaction levels and socio-demographic/clinical factors. Individuals with lower education levels, no substance use, minimal alcohol consumption, and suppressed viral loads reported higher satisfaction scores.ConclusionThis study highlights the potential for personalizing HIV treatment strategies based on socio-demographic and clinical factors. Findings emphasize the need to promote healthy lifestyles, enhance health literacy, and implement anti-addiction programs to improve treatment adherence and satisfaction among PLWH. Based on the findings, there is a need to develop strategies aimed at improving treatment satisfaction and outcomes in HIV management.

Transforming HIV Care: Adapting the Health4All Module to Combat the Stigma Among Malaysian Primary Healthcare Workers.

Globally, stigma and discrimination in healthcare settings have been identified as significant barriers to implementing HIV prevention and treatment strategies. However, research on interventions to reduce the stigma in healthcare facilities, particularly in Malaysia, is lacking. Hence, this study aims to bridge these gaps by implementing a globally accepted training module to reduce HIV stigma among healthcare workers (HCWs). This study aims to implement the Health4All module to reduce HIV stigma among HCWs in Malaysia. A randomized controlled trial (RCT) study with repeated measures over a period of six months was conducted to implement the Health4All module and evaluate the study outcomes. The implementation process involved a total of 300 randomly selected HCWs from 10 primary health clinics in the study area. A total of 263 respondents participated at the beginning, giving a response rate of 88%, but only 177 completed records were used for the final analysis. The mean score for perceived risk and fear was reduced by 1.07between baseline and one month (p < 0.001) and reduced further by 0.81 between one month and three months (p < 0.05). The mean score for value-driven stigma was reduced by 2.31 between baseline and one month (p < 0.001) and reduced further by 0.86 between one month and three months (p = 0.25). The mean score for discriminatory attitude was reduced by 1.65 between baseline and one month (p = 0.002) and reduced further by 1.65 between one month and three months (p = 0.002). The Health4All module was effective in reducing the HIV stigma among HCWs over three months. This study suggests that the training program can be replicated across different healthcare settings worldwide for wider implementation.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Impact of methamphetamine use on HIV and other health outcomes at an urban HIV medicine clinic.

The methamphetamine epidemic threatens progress towards ending the HIV epidemic in the United States. Further characterizing the prevalence and impact of methamphetamine use among people with HIV (PWH) is necessary to inform integrated HIV and methamphetamine treatment strategies. We conducted a retrospective chart review to characterize methamphetamine use among 3092 PWH at an urban HIV Medicine clinic between July 1, 2022 and June 30, 2023. The chi-squared test was utilized to assess for statistically significant differences in demographics and HIV and other health outcomes among PWH who use and do not use methamphetamine. The prevalence of methamphetamine use among PWH in this cohort was 17%. PWH who used methamphetamine were more likely to be <40 years of age, identify as White race, live in neighborhoods with low Healthy Places Index scores, identify as lesbian, gay, or bisexual, report male sex with men (MSM), MSM and injection drug use (IDU), or IDU as HIV transmission risk factor, miss scheduled HIV primary care visits, and screen positive for hepatitis C virus antibody, gonorrhea, chlamydia, and major depressive disorder. PWH who use methamphetamine were also less likely to be virally suppressed and have a CD4 + cell count ≥200 cells/mm 3 . Methamphetamine use is prevalent among PWH at this urban HIV Medicine Clinic and is associated with worse HIV and other health outcomes which likely increase the risk of HIV transmission. The integration of methamphetamine use disorder treatment into HIV primary care is necessary to work toward ending the syndemics of methamphetamine and HIV.

CRF08_BC subtype is more prone to ART failure and new-generation NNRTI-resistance under long-term first-line ART

ObjectiveTo investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. MethodsPatients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. ResultsSix HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. ConclusionsThe present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier

BackgroundAppropriate interactions between antiretroviral therapies (ART) and drug transporters and metabolizing enzymes at the blood brain barrier (BBB) are critical to ensure adequate dosing of the brain to achieve HIV suppression. These proteins are modulated by demographic and lifestyle factors, including substance use. While understudied, illicit substances share drug transport and metabolism pathways with ART, increasing the potential for adverse drug:drug interactions. This is particularly important when considering the brain as it is relatively undertreated compared to peripheral organs and is vulnerable to substance use-mediated damage.MethodsWe used an in vitro model of the human BBB to determine the extravasation of three first-line ART drugs, emtricitabine (FTC), tenofovir (TFV), and dolutegravir (DTG), in the presence and absence of cocaine, which served as our illicit substance model. The impact of cocaine on BBB integrity and permeability, drug transporters, metabolizing enzymes, and their master transcriptional regulators were evaluated to determine the mechanisms by which substance use impacted ART central nervous system (CNS) availability.ResultsWe determined that cocaine had a selective impact on ART extravasation, where it increased FTC’s ability to cross the BBB while decreasing TFV. DTG concentrations that passed the BBB were below quantifiable limits. Interestingly, the potent neuroinflammatory modulator, lipopolysaccharide, had no effect on ART transport, suggesting a specificity for cocaine. Unexpectedly, cocaine did not breach the BBB, as permeability to albumin and 4 kDa FITC-dextran, as well as tight junction proteins and adhesion molecules remained unchanged. Rather, cocaine selectively decreased the pregnane-x receptor (PXR), but not constitutive androstane receptor (CAR). Consequently, drug transporter expression and activity decreased in endothelial cells of the BBB, including p-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 4 (MRP4). Further, cytochrome P450 3A4 (CYP3A4) enzymatic activity increased following cocaine treatment that coincided with decreased expression. Finally, cocaine modulated adenylate kinases that are required to facilitate biotransformation of ART prodrugs to their phosphorylated, pharmacologically active counterparts.ConclusionOur findings indicate that additional considerations are needed in CNS HIV treatment strategies for people who use cocaine, as it may limit ART efficacy through regulation of drug transport and metabolizing pathways at the BBB.

Trends and the associated factors of optimal immunological response and virological response in late anti-retroviral therapy initiation HIV cases in Taiwan from 2009 to 2020

BackgroundLate cART initiation (CD4 count ≤200 cells/μL or AIDS-defining opportunistic illnesses [AOIs] at cART initiation) impedes CD4 count recovery and virologic suppression after cART initiation. However, studies to evaluate trends of and modifiable factors for optimal immunological response (IR) and virological response (VR) in people living with HIV (PLWH) with late cART initiation with the current HIV treatment strategies are limited. MethodsWe retrospectively identified 475 PLWH with late cART initiation in 2009–2020. Patients were grouped based on the presence of IR (CD4 count ≥200 cells/μL) or VR (plasma viral load [PVL] ≤ 50 copies/mL) within 18 months after cART initiation (403 [84.8%] IR(+) and 72 [15.2%] IR(−); 422 [88.8%] VR(+) and 53 [11.2%] VR(−)). We used Joinpoint regression to identify IR (+) and VR(+) proportion changes. ResultsFrom 2009 to 2020, the proportion of IR(+) patients remained unchanged (75% to 90%, P = 0.102), whereas that of VR(+) patients increased significantly (75% to 95%, P = 0.007). No join point was identified for either IR(+) or VR(+), and the annual percentage change was 0.56% (nonsignificant) and 1.35% (significant) for IR(+) and VR(+), respectively. Compared to IR(−) patients, IR(+) patients were more likely to have a higher pre-cART PVL, to start with a first-line INSTI-based regimen, or to start cART within 14 days of HIV diagnosis but were less likely to have chronic kidney disease, composite AOIs, or a lower pre-cART CD4 count. Compared to VR(−) patients, VR(+) patients were more likely to start a single-tablet regimen but were less likely to have a higher pre-cART PVL. ConclusionsOur study identified several modifiable factors for optimal IR (rapid cART initiation and INSTI-based regimen initiation) and for optimal VR (STR initiation) among late initiators, which may guide early treatment modifications to reduce their AIDS-defining event incidence and mortality.

Facilitating Access to Art and Pre-exposure Prophylaxis for LGBTQ Individuals in Combating HIV in Malaysia: An Analysis from a Shariah Perspective

The increasing rate of new HIV infections poses a significant public health challenge, particularly among young individuals engaging in high-risk sexual behaviours, including male-to-male interactions. Effectively addressing HIV prevention and management within the LGBT community in Malaysia necessitates a comprehensive approach that considers both medical and socio-cultural aspects. This academic inquiry seeks to comprehensively evaluate the progress in HIV preventive measures and therapeutic interventions in the Malaysian context, examining their effectiveness within the affected communities and their adherence to Sharia principles despite religious barriers to modern medical approaches. The findings of this study indicate that the implementation of Antiretroviral Therapy (ART) and Pre-Exposure Prophylaxis (PrEP) measures, supported by the Ministry of Health, align with Sharia principles, underscoring the importance of disease prevention, treatment, and harm reduction. Nonetheless, the research emphasises the vital role of integrating Islamic practices as a preventive measure against HIV transmission. Consequently, this study advocates for improving HIV prevention and treatment strategies pursued by the Ministry of Health by integrating Islamic ethical considerations into Malaysia’s public health policies.

Levels and Predictors of Unsuppressed Viremia among People Living with HIV on ART in an Urban Population of North-Central Nigeria: A Retrospective Cross-sectional Study

Achieving viral suppression is crucial for the effective management of HIV. We investigated the prevalence and predictors of unsuppressed viremia among adults living with HIV (PLHIV) on antiretroviral therapy (ART) in the urban city of Jos, Plateau State, North-central Nigeria. A cross-sectional study was conducted with 2,748 PLHIV, comprising 1,902 females (69.2%) and 846 males (30.8%). The majority (71.0%) were aged 36-55 years. Most participants (88.1%) were on the first-line ART regimen tenofovir disoproxil fumarate-lamivudine-dolutegravir (TDF+3TC+DTG), with 6.0% on second-line regimens. The prevalence of unsuppressed viremia (viral load &gt;1,000 copies/mL) was assessed, and predictors were identified using chi-square tests and logistic regression analyses. Overall prevalence of unsuppressed viremia was 4.0% (110 participants), with higher proportions among males (5.6%) compared to females (3.3%) and among those aged 18-35 years (7.9%) compared to other age groups. PLHIV on first-line TDF+3TC+DTG ART had the lowest level of unsuppressed viremia (2.6%). Chi-square tests revealed significant associations between unsuppressed viremia and gender (χ2=7.67, p=0.01), age group (χ2=13.19, p=0.01), and ART regimen (χ2=110.97, p=0.0001). Multivariate logistic regression identified males (AOR=1.69; 95% CI: 1.12-2.56), younger age groups (18-35 years: AOR=12.96; 95% CI: 2.12-79.09 and 36-45 years: AOR=12.84; 95% CI: 3.70-44.64), and non-TDF+3TC+DTG regimens as significant predictors of unsuppressed viremia. The study highlights the effectiveness of the TDF+3TC+DTG regimen and the need for targeted interventions to address disparities in viral suppression, particularly among males and younger individuals. These findings are crucial for optimizing HIV treatment strategies and improving health outcomes for PLHIV in urban areas of low-and-middle-income countries.

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China.

Antiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children. From January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2-4 adverse events and abnormal laboratory test results. A total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5-10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3-4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5-6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108-4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004-3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299-5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238-0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2-4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children. Our research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

Characterizing the Relationship between HIV Peer Support Groups and Internalized Stigma Among People Living with HIV in Nigeria.

HIV-related stigma remains a significant barrier to implementing effective HIV treatment and prevention strategies in Nigeria. Despite the high uptake of peer support groups among people living with HIV (PLHIV) in Nigeria, the potential role of such peer support on the burden of internalized stigma remains understudied. To address this gap, we conducted a secondary analysis of the PLHIV Stigma Index 2.0, a socio-behavioral survey implemented by PLHIV led-organizations to assess the relationship between group membership and internalized stigma. Internalized stigma was measured using the Internalized AIDS-related Stigma Scale. Multinomial logistic regression was used to measure the association between self-reported engagement in peer support groups and internalized stigma adjusting for age, education, duration since HIV diagnosis, employment, disclosure status, and sex-work engagement. Of the 1,244 respondents in this study, 75.1% were engaged in HIV peer support groups. Over half (55.5%) and about one-fourth (27.3%) demonstrated low/moderate and high levels of internalized stigma, respectively. PLHIV engaged in HIV peer support groups were less likely to report both low/moderate (versus no) (adjusted odds ratio (aOR): 0.47 [95% CI: 0.27 to 0.81]; p = 0.006) and high (versus no) (aOR: 0.30 [95% CI: 0.17 to 0.53]; p < 0.001) levels of internalized stigma compared to those not engaged. In this study, the burden of internalized stigma is high among PLHIV in Nigeria. However, engagement in peer support groups appears to mitigate these stigmas. Stigma mitigation strategies to increase peer support may represent a critical tool in decreasing sustained HIV treatment gaps among PLHIV in Nigeria.

Evaluating the use of generalized dynamic weighted ordinary least squares for individualized HIV treatment strategies

Evaluating the use of generalized dynamic weighted ordinary least squares for individualized HIV treatment strategies

Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa.

Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

Bibliometric and visualized analysis of elite controllers based on CiteSpace: landscapes, hotspots, and frontiers.

A unique subset of people living with HIV, known as elite controllers, possess spontaneous and consistent control over viral replication and disease progression in the absence of antiviral intervention. In-depth research on elite controllers is conducive to designing better treatment strategies for HIV. However, comprehensive and illuminating bibliometric reports on elite controllers are rare. Articles on elite controllers were retrieved from the Web of Science Core Collection. A visualized analysis of this domain was conducted by CiteSpace software. Taking count, betweenness centrality, and burst value as criteria, we interpreted the visualization results and predicted future new directions and emerging trends. By December 31, 2022, 843 articles related to elite controllers had been published. The largest contributors in terms of country, institution, and author were the United States (485), Univ Calif San Francisco (87), and Walker B.D. (65), respectively. Migueles S.A. (325) and Journal of Virology (770) were the most cocited author and journal, respectively. Additionally, by summarizing the results of our CiteSpace software analysis on references and keywords, we considered that the research hotspots and frontiers on elite controllers mainly focus on three aspects: deciphering the mechanisms of durable control, delineating the implications for the development of treatments for HIV infection, and highlighting the clinical risks faced by elite controllers and coping strategies. This study performed a bibliometric and visual analysis of elite controllers, identified the main characteristics and emerging trends, and provided insightful references for further development of this rapidly evolving and complex field.

Deep-sequencing of viral genomes from a large and diverse cohort of treatment-naive HIV-infected persons shows associations between intrahost genetic diversity and viral load.

Infection with human immunodeficiency virus type 1 (HIV) typically results from transmission of a small and genetically uniform viral population. Following transmission, the virus population becomes more diverse because of recombination and acquired mutations through genetic drift and selection. Viral intrahost genetic diversity remains a major obstacle to the cure of HIV; however, the association between intrahost diversity and disease progression markers has not been investigated in large and diverse cohorts for which the majority of the genome has been deep-sequenced. Viral load (VL) is a key progression marker and understanding of its relationship to viral intrahost genetic diversity could help design future strategies for HIV monitoring and treatment. We analysed deep-sequenced viral genomes from 2,650 treatment-naive HIV-infected persons to measure the intrahost genetic diversity of 2,447 genomic codon positions as calculated by Shannon entropy. We tested for associations between VL and amino acid (AA) entropy accounting for sex, age, race, duration of infection, and HIV population structure. We confirmed that the intrahost genetic diversity is highest in the env gene. Furthermore, we showed that mean Shannon entropy is significantly associated with VL, especially in infections of >24 months duration. We identified 16 significant associations between VL (p-value<2.0x10-5) and Shannon entropy at AA positions which in our association analysis explained 13% of the variance in VL. Finally, equivalent analysis based on variation in HIV consensus sequences explained only 2% of VL variance. Our results elucidate that viral intrahost genetic diversity is associated with VL and could be used as a better disease progression marker than HIV consensus sequence variants, especially in infections of longer duration. We emphasize that viral intrahost diversity should be considered when studying viral genomes and infection outcomes. Samples included in this study were derived from participants who consented in the clinical trial, START (NCT00867048) (23), run by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). All the participant sites are listed here: http://www.insight-trials.org/start/my_phpscript/participating.php?by=site.

Trends of late HIV presentation and advance HIV disease among newly diagnosed HIV cases in Jiangsu, China: A serial cross-sectional study from 2008 to 2020.

This study aimed to assess the trends and determine the factors associated with late presentation (LP) and advanced HIV disease (AHD) among newly diagnosed people living with HIV (PLWH) from 2008 to 2020 in Jiangsu, China. Newly diagnosed PLWH registered in the HIV surveillance system from 2008 to 2020 were included. Multivariable logistic regression models were used to analyze the factors associated with LP and AHD. The LP and AHD trends were assessed using Joint-point analysis. Of 37,251 newly diagnosed PLWH identified, 30,251(81.2%) patients met the inclusion criteria. Among those, 16,672 (55.1%) were considered LP, and 8,691 (28.7%) had AHD. LP trends steadily increased from 2008 (39.0%) to 2020 (59.4%), but AHD trends decreased visibly from 2016 (32.3%) to 2020 (23.4%). The overall median CD4 trends decreased slowly from 389 to 305 cells/mm3 between 2008 and 2020. Married patients and those older than 35 years were more likely to be LP and have AHD. Patients infected via heterosexual transmission had a higher risk of being classified as AHD (aOR: 1.13, 95%CI: 1.06-1.21) than patients infected via homosexual transmission. Patients that were diagnosed at sexually transmitted infections (STIs) clinics (aOR: 1.10, 95%CI: 1.01-1.20) and in hospitals (aOR: 1.69, 95%CI: 1.59-1.79) were more likely to be classified as LP compared with patients diagnosed at voluntary counseling and testing (VCT) centers. Similar, patients diagnosed at STIs clinics (aOR: 1.23, 95%CI: 1.11-1.36) and hospitals (aOR: 2.27, 95%CI: 2.12-2.43) were more likely to have AHD than patients diagnosed in VCT. Our findings indicate an alarming burden of LP in Jiangsu, suggesting the need for more attention toward HIV diagnosis at early CD4 stages. National HIV control programs must strengthen comprehensive interventions for HIV prevention and promote HIV services. Also, strategies for HIV prevention (PrEP and PEP), testing, and treatment must be extended, especially among the general population.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.

Targeted Nanocarrier Delivery of RNA Therapeutics to Control HIV Infection.

Our understanding of HIV infection has greatly advanced since the discovery of the virus in 1983. Treatment options have improved the quality of life of people living with HIV/AIDS, turning it from a fatal disease into a chronic, manageable infection. Despite all this progress, a cure remains elusive. A major barrier to attaining an HIV cure is the presence of the latent viral reservoir, which is established early in infection and persists for the lifetime of the host, even during prolonged anti-viral therapy. Different cure strategies are currently being explored to eliminate or suppress this reservoir. Several studies have shown that a functional cure may be achieved by preventing infection and also inhibiting reactivation of the virus from the latent reservoir. Here, we briefly describe the main HIV cure strategies, focussing on the use of RNA therapeutics, including small interfering RNA (siRNA) to maintain HIV permanently in a state of super latency, and CRISPR gRNA to excise the latent reservoir. A challenge with progressing RNA therapeutics to the clinic is achieving effective delivery into the host cell. This review covers recent nanotechnological strategies for siRNA delivery using liposomes, N-acetylgalactosamine conjugation, inorganic nanoparticles and polymer-based nanocapsules. We further discuss the opportunities and challenges of those strategies for HIV treatment.