The rollout of paediatric dolutegravir and virological outcomes among children living with HIV in Mozambique.

Background: In 2022, Mozambique introduced Dolutegravir 10mg (pDTG), as part of paediatric antiretroviral therapy for children weighing < 20 kg. Understanding real-world challenges during national rollout can strengthen health systems in resource-limited settings. Objectives: We described the transition rate to, and new initiation of, pDTG, viral load suppression (VLS) post-pDTG, and factors associated with VLS among children living with HIV. Method: We conducted a retrospective cohort study involving children aged < 9 years and abstracted data from clinical sources. We used logistic regression to assess VLS and pDTG initiation predictors. Results: Of 1353 children, 1146 initiated pDTG; 196 (14.5%) had no recorded weight. Post-pDTG switch, 98.9% (950/961) of children maintained the same nucleoside reverse transcriptase inhibitor backbone. After initiating Abacavir/Lamivudine+pDTG, 834 (72.8%) children remained on the regimen, 156 (13.6%) switched off (majority to Dolutegravir 50mg), 22 (1.9%) had ≥ 2 anchor drug switches; 134 (11.7%) had no documented follow-up regimen. Factors associated with pDTG initiation or switch were younger age (adjusted odds ratio [AOR] = 0.71 [0.63-0.80]) and a recorded weight (AOR = 55.58 [33.88-91.18]). VLS among the 294 children with a viral load (VL) test after ≥ 5 months post-pDTG was 75.5% (n = 222/294). Pre-pDTG VLS rate among treatment-experienced children was 56.5% (n = 130/230). Factors associated with VLS were older age (AOR = 1.18 [1.03-1.34]) and previous VLS (AOR = 2.27 [1.27-4.06]). Conclusion: Most eligible children initiated pDTG per guidelines, improving post-pDTG VLS. Challenges included unexplained switches off pDTG after initiation, low VL coverage and inadequate documentation in clinic records.

Rhabdomyolysis in Acute HIV Infection.

Rhabdomyolysis is a rare but potentially life-threatening complication of acute HIV infection. We present a case report of a young adult male who presented with fever, myalgia, and elevated creatine phosphokinase levels, ultimately diagnosed with acute HIV infection-associated rhabdomyolysis. This case highlights the importance of considering HIV infection in the differential diagnosis of rhabdomyolysis, particularly in at-risk populations, even in the absence of typical HIV-related symptoms.

Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV.

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.

New Horizons in Antiretroviral Drug Delivery Systems for HIV Management

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of the circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. OBJECTIVE: This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented, along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. CONCLUSION: This review examines innovative approaches for HIV treatment, where various drug delivery systems have shown significant advantages, such as high drug encapsulation, improved solubility, and enhanced bioavailability both in vitro and in vivo. Strategies like cyclodextrins, solid dispersions, microneedles, and nanoparticles are explored to address challenges in drug solubility, bioavailability, and administration routes. Despite progress, obstacles like limited clinical trials and industrial scalability hinder the widespread adoption of these formulations, emphasizing the need for further research and collaboration to optimize and ensure accessibility of innovative HIV therapies, mainly in regions where access to HIV treatment is scarce and remains a challenge.

Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.

BACKGROUND: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention. METHODS: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted. RESULTS: If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place. CONCLUSIONS: Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020.

Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy.

INTRODUCTION: Increasing drug resistance and the absence of a cure necessitates exploration of novel treatment strategies for people living with HIV (PLWH). Targeting of soluble co-inhibitory immune checkpoint molecules (sICMs) represents a novel, potentially effective strategy in the management of HIV. METHODS: In this retrospective, longitudinal, observational study, the plasma levels of five prominent co-inhibitory sICMs-CTLA-4, LAG-3, PD-1 and its ligand PD-L1, as well as TIM-3-were quantified in 68 PLWH-before and one year after antiretroviral therapy (ART)-and compared with those of 15 healthy control participants. RESULTS: Relative to control participants, PLWH had substantially elevated pre-treatment levels of all five co-inhibitory sICMs (p < 0.0001-p < 0.0657), which, over the 12-month period of ART, remained significantly higher than those of controls (p < 0.0367-p < 0.0001). PLWH with advanced disease, reflected by a CD4+ T cell count <200 cells/mm3 before ART, had the lowest levels of CTLA-4 and LAG-3, while participants with pre-treatment HIV viral loads ≥100,000 copies/mL had higher pre-treatment levels of TIM-3, which also persisted at 12 months. CONCLUSIONS: Plasma levels of CTLA-4, LAG-3, PD-1, PD-L1 and TIM-3 were significantly elevated in treatment-naïve PLWH and remained so following one year of virally-suppressive ART, possibly identifying LAG-3 and TIM-3 in particular as potential targets for adjuvant immunotherapy.

Strengthening person-centered care through quality improvement: a mixed-methods study examining implementation of the Person-Centered Care Assessment Tool in Zambian health facilities.

INTRODUCTION: Person-centered care (PCC) is considered a fundamental approach to address clients' needs. There is a dearth of data on specific actions that HIV treatment providers identify as priorities to strengthen PCC. OBJECTIVE: This study team developed the Person-Centered Care Assessment Tool (PCC-AT), which measures PCC service delivery within HIV treatment settings. The PCC-AT, including subsequent group action planning, was implemented across 29 facilities in Zambia among 173 HIV treatment providers. Mixed-methods study objectives included: (1) identify types of PCC-strengthening activities prioritized based upon low and high PCC-AT scores; (2) identify common themes in PCC implementation challenges and action plan activities by low and high PCC-AT score; and (3) determine differences in priority actions by facility ART clinic volume or geographic type. METHODS: The study team conducted thematic analysis of action plan data and cross-tabulation queries to observe patterns across themes, PCC-AT scores, and key study variables. RESULTS: The qualitative analysis identified 39 themes across 29 action plans. A higher proportion of rural compared to urban facilities identified actions related to stigma and clients' rights training; accessibility of educational materials and gender-based violence training. A higher proportion of urban and peri-urban compared to rural facilities identified actions related to community-led monitoring. DISCUSSION: Findings provide a basis to understand common PCC weaknesses and activities providers perceive as opportunities to strengthen experiences in care. CONCLUSION: To effectively support clients across the care continuum, systematic assessment of PCC services, action planning, continuous quality improvement interventions and re-measurements may be an important approach.

HIV-associated rectovaginal fistulae in children: a single-centre retrospective study in the antiretroviral era.

PURPOSE: Acquired rectovaginal fistulae (RVF) are a complication of paediatric HIV infection. We report our experience with the surgical management of this condition. METHODS: We retrospectively reviewed the records of paediatric patients with HIV-associated RVF managed at Chris Hani Baragwanath Academic Hospital (2011-2023). Information about HIV management, surgical history, and long-term outcomes was collected. RESULTS: Ten patients with HIV-associated RVF were identified. Median age of presentation was 2 years (IQR: 1-3 years). Nine patients (9/10) underwent diverting colostomy, while one demised before the stoma was fashioned. Fistula repair was performed a median of 17 months (IQR: 7.5-55 months) after colostomy. An ischiorectal fat pad was interposed in 5/9 patients. Four (4/9) patients had fistula recurrence, 2/9 patients developed anal stenosis, and 3/9 perineal sepsis. Stoma reversal was performed a median of 16 months (IQR: 3-25 months) after repair. Seven patients (7/9) have good outcomes without soiling, while 2/9 have long-term stomas. Failure to maintain viral suppression after repair was significantly associated with fistula recurrence and complications (φ = 0.8, p < 0.05). CONCLUSION: While HIV-associated RVFs remain a challenging condition, successful surgical treatment is possible. Viral suppression is a necessary condition for good outcomes.

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

BACKGROUND: Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. METHODS: Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. FINDINGS: We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. INTERPRETATION: In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Factors associated with antiretroviral treatment adherence among people living with HIV in Guangdong Province, China: a cross sectional analysis.

BACKGROUND: Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the "test and treat" era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. METHODS: Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants' self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. RESULTS: A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01-3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09-4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27-4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03-3.19), no social participation (aOR = 5.65, 95%CI: 1.71-18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26-0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P < 0.001) between ART adherence and the latent psychosocial (syndemic) factor, which consisted of the three latent factors of medication beliefs and self-efficacy (standardized coefficient = 0.65, P < 0.001), supportive environment (standardized coefficient = 0.50, P < 0.001), and negative emotions (standardized coefficient=-0.38, P < 0.01). The latent factors of medication beliefs and self-efficacy, supportive environment, and negative emotions explained 42.3%, 25.3%, and 14.1% of the variance in the latent psychosocial factor, respectively. CONCLUSIONS: About nine out of ten PLHIV on ART in Guangdong Province self-reported optimal ART adherence. However, more efforts should be made to address barriers to optimal ART adherence.

Definition of Virological Endpoints Improving the Design of Human Immunodeficiency Virus (HIV) Cure Strategies Using Analytical Antiretroviral Treatment Interruption.

BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint. METHODS: We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude-related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control. RESULTS: Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion. CONCLUSIONS: Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint.

Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy.

BACKGROUND: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. METHODS: PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. RESULTS: Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). CONCLUSIONS: For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy.

Investigating the Barriers and Facilitators to Using Antiretroviral Therapy among Women Living with HIV in Plateau State, Nigeria.

BACKGROUND: Women and girls account for more than 50% of the global HIV population. In Nigeria, the proportion of women living with HIV on long-term antiretroviral therapy (ART) has been on the rise. Despite this, little research exists on their experiences regarding antiretroviral therapy use, especially for women living with HIV (WLHIV) in Plateau State, Nigeria. This study investigates the barriers and facilitators influencing antiretroviral therapy use among women living with HIV. METHODS: This study employed a qualitative research design, using focus groups, and included women (female sex workers, pregnant and non-pregnant women living with HIV) and the male partners of serodiscordant couples. Eligibility criteria were being 18 years of age or older, on antiretroviral therapy for more than one year/on pre-exposure prophylaxis (PrEP) for more than one month, and speaking English, Hausa, or both. Data coding utilized both inductive and deductive approaches, and standard content analysis was applied to develop emerging themes. RESULTS: Of the 106 participants, 88 were women living with HIV, and 18 were men in serodiscordant couples. The first facilitator shared by the participants was feeling healthier and stronger due to the antiretroviral therapy, which was also expressed by the male participants on PrEP as feeling good while taking the drug. Additional facilitators shared by the participants included weight gain and having a more positive outlook on life. Participants also disproportionately described barriers to using antiretroviral therapy, including experiences with emotional challenges, physical discomfort, and side effects of ART. Such barriers were linked to feelings of past regret, frustration, and disappointment. CONCLUSION: This study underscores the significance of maintaining a positive perspective on ART use, demonstrated by the connection between a positive outlook and weight gain, and highlights the hurdles that Plateau State's women living with HIV face in adhering to antiretroviral therapy. Policymakers and healthcare providers can utilize these findings to formulate targeted strategies aimed at minimizing identified barriers and enhancing antiretroviral therapy utilization among this population via peer- support groups, economic empowerment, and psychosocial support.

Understanding HIV/AIDS dynamics: insights from CD4+T cells, antiretroviral treatment, and country-specific analysis.

In this article, we present a mathematical model for human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS), taking into account the number of CD4+T cells and antiretroviral treatment. This model is developed based on the susceptible, infected, treated, AIDS (SITA) framework, wherein the infected and treated compartments are divided based on the number of CD4+T cells. Additionally, we consider the possibility of treatment failure, which can exacerbate the condition of the treated individual. Initially, we analyze a simplified HIV/AIDS model without differentiation between the infected and treated classes. Our findings reveal that the global stability of the HIV/AIDS-free equilibrium point is contingent upon the basic reproduction number being less than one. Furthermore, a bifurcation analysis demonstrates that our simplified model consistently exhibits a transcritical bifurcation at a reproduction number equal to one. In the complete model, we elucidate how the control reproduction number determines the stability of the HIV/AIDS-free equilibrium point. To align our model with the empirical data, we estimate its parameters using prevalence data from the top four countries affected by HIV/AIDS, namely, Eswatini, Lesotho, Botswana, and South Africa. We employ numerical simulations and conduct elasticity and sensitivity analyses to examine how our model parameters influence the control reproduction number and the dynamics of each model compartment. Our findings reveal that each country displays distinct sensitivities to the model parameters, implying the need for tailored strategies depending on the target country. Autonomous simulations highlight the potential of case detection and condom use in reducing HIV/AIDS prevalence. Furthermore, we identify that the quality of condoms plays a crucial role: with higher quality condoms, a smaller proportion of infected individuals need to use them for the potential eradication of HIV/AIDS from the population. In our optimal control simulations, we assess population behavior when control interventions are treated as time-dependent variables. Our analysis demonstrates that a combination of condom use and case detection, as time-dependent variables, can significantly curtail the spread of HIV while maintaining an optimal cost of intervention. Moreover, our cost-effectiveness analysis indicates that the condom use intervention alone emerges as the most cost-effective strategy, followed by a combination of case detection and condom use, and finally, case detection as a standalone strategy.

The impact of antiretroviral treatment and child-focused unconditional cash transfers on child mortality.

Although there is sufficient evidence in the epidemiological literature that antiretroviral treatment (ART) reduces child mortality, there is limited evidence of its effect in the socio-economic determinants of child mortality literature. Furthermore, evidence on the effect of child focused unconditional cash transfers (UCTs) on child mortality is limited, especially in the African context. Using South Africa's provincial level data over the period 2001 to 2019, we evaluate the effect of ART and child focused UCTs on child mortality. We use the two-stage instrumental variable mean group estimator. We find that ART reduces child mortality. Moreover, we find an inverted U-shaped non-linear relationship between UCTs and child mortality that is contingent to the level of cash transfer coverage. Our analyses also reveal that UCTs improve the effect of ART on child mortality by enhancing access and adherence to treatment. While the focus of our analyses was on the child mortality effects of ART and UCTs, our findings reaffirm the well-documented impacts of factors such as public health expenditure, HIV/AIDS, female education, and health worker density on child mortality. Collectively, the combination of high ART and UCTs coverage, increased public health expenditure, enhanced female education, and improved health worker density, represents value for money for policymakers and funders. These areas should be prioritised to improve child well-being.

Heavily treatment-experienced persons living with HIV currently in care in Italy: characteristics, risk factors, and therapeutic options-the ICONA Foundation cohort study.

OBJECTIVES: Heavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021. METHODS: HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories. RESULTS: Among the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio [OR] 1.60 per 100 cells/mmc lower CD4, 95% confidence interval [CI] 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count <200 cells/mmc or VL>200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count <200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one antiretroviral drug class. CONCLUSIONS: HTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new antiretroviral drugs.

Difficult-to-treat HIV in Sweden: a cross-sectional study.

BACKGROUND: Our aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV. METHODS: In this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) ≥ 2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health). RESULTS: Nine percent of the Swedish HIV cohort in 2023 (n = 8531) met at least one criterion for difficult-to-treat HIV. Most of them had ≥ 2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p = 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group. CONCLUSIONS: Although 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.

Policy and Programming Towards Addressing Treatment Gaps in Adolescents Living with HIV: A Content Analysis of Policy and Programme Documents in Namibia.

Adolescents living with HIV (ALHIV) face unique challenges resulting in persistent treatment gaps, particularly viral non-suppression. Country programs adopt policies, guidelines, and innovations, based on WHO recommendations and best practices from elsewhere. However, it is unclear to what extent these tools address the management of adolescents with viral non-suppression. We report on a review of guidelines for the provision of HIV services to ALHIV in Namibia. We conducted a systematic document review using Content Analysis and Thematic Analysis methodology, and the READ approach. We identified seven relevant policy documents, four of which somewhat addressed viral non-suppression (treatment gap) in ALHIV and outlined interventions to improve treatment outcomes in adolescents considering their lived experience and unique challenges. The persistent treatment gap may reflect policy implementation gaps in specifically addressing viral non-suppression. It may be worthwhile to leverage existing documents to develop specific operational guidance for ALHIV with unsuppressed viral loads.

Study analysing the potential gaps in the contents of policies and programme documents meant to address management of adolescents living with HIV with high viral load Viral load suppression is a huge challenge in adolescents living with HIV (ALHIV). Globally, adolescents lag when compared to children and adults in achieving viral suppression levels set for achieving HIV epidemic control. The WHO and global HIV program initiatives recommend evidence-based interventions to be included in policies and guidelines to address unique barriers adolescents face that prevent them from staying in HIV care and adhering to their medication. The extent to which country policies guide service providers in managing high viral load cases among adolescents is important in identifying and addressing the persistent gaps. We reviewed the contents of policies, guidelines and other programmatic documents that address HIV management in adolescents in Namibia to assess the extent to which the documents guide management of ALHIV who have high viral load. Seven documents addressing management of ALHIV in Namibia were identified. Four documents address viral suppression among adolescents and recommend some interventions to improve treatment outcomes in adolescents in general. The documents acknowledge the uniqueness of the adolescence, with unique experiences and challenges. However, the documents fall short in providing comprehensive and specific guidance in managing adolescents with high viral loads, for program implementers and direct service providers for ALHIV. The fragmented guidance on managing adolescents with unsuppressed viral loads may be leading to implementation gaps or uncertainties among service providers on how to manage unique cases. It would be essential to focus future efforts on consolidation or development of comprehensive guidance on management of adolescents with high viral load, and capacitating the healthcare providers and stakeholders engaged in addressing social determinants of health affecting these adolescents. A multisectoral approach may provide a pathway to improved viral suppression among ALHIV.

Avances en el tratamiento de los niños y adolescentes con infección por HIV / Advances in the treatment of children and adolescents with HIV infection

El uso de antirretrovirales (ARV) en el embarazo, el parto y el recién nacido y la aplicación de tratamientos combinados en los niños se han asociado con una disminución del sida en pediatría y el aumento de la sobrevida. La introducción de los inhibidores de integrasa en una dosis diaria ha eliminado barreras para la adherencia, pero los medicamentos orales diarios continúan planteando problemas de privacidad y estigma. Las nuevas tecnologías de administración de los medicamentos y las nuevas drogas junto con la combinación de ARV y los anticuerpos ampliamente neutralizantes (bNAb), ofrecen un potencial de opciones futuras para el tratamiento pediátrico del HIV. Los bNAb son anticuerpos que pueden reconocer diferentes tipos de HIV, bloquear su entrada en las células sanas y ayudar a destruir las células ya infectadas, pueden administrarse por vía parenteral y constituyen un enfoque novedoso y seguro con potencial para el tratamiento y la prevención del HIV, incluida la transmisión vertical. En los lactantes que contraen HIV, los bNAb podrían ofrecer ventajas terapéuticas al reducir el reservorio del virus, mejorar la inmunidad adquirida y, en el futuro, proporcionar un camino hacia la cura funcional. Dentro de los ARV inyectables de acción prolongada, cabotegravir/ rilpivirina se ha incorporado en las guías internacionales de adultos y adolescentes tanto para el tratamiento como para la prevención. A medida que el tratamiento del HIV en adultos va evolucionando, es fundamental asegurar que los neonatos, lactantes, niños y adolescentes tengan acceso a las mejores opciones de tratamiento y prevención a lo largo de su vida (AU)

The use of antiretrovirals (ARVs) during pregnancy, delivery, and in the newborn and the use of combination therapy in children have been associated with a decrease in pediatric AIDS and increased survival. The introduction of once-daily integrase inhibitors has removed barriers to adherence, but daily oral medications continue to pose privacy and stigma issues. New drug delivery technologies and new drugs along with the combination of ARVs and broadly neutralizing antibodies (bNAbs) offer potential future options for pediatric HIV treatment. bNAbs are antibodies that can recognize different types of HIV, block their entry into healthy cells and help destroy already infected cells, can be delivered parenterally, and represent a novel and safe approach with potential for the treatment and prevention of HIV, including mother-to-child transmission. In infants who contract HIV, bNBAs could offer therapeutic advantages by reducing the viral reservoir, enhancing acquired immunity and, in the future, providing a pathway to a functional cure. Within the long-acting injectable ARVs, cabotegravir/rilpivirine has been incorporated into international guidelines for adults and adolescents for both treatment and prevention. As adult HIV treatment evolves, it is critical to ensure that newborns, infants, children and adolescents have access to the best treatment and prevention options throughout their lives (AU)

"This Is Actually a Really Unique Moment in Time": Navigating Long-Acting HIV Treatment and HIV Cure Research with Analytical Treatment Interruptions-A Qualitative Interview Study in the United States.

Advancements in long-acting (LA) HIV treatment and cure research with analytical treatment interruptions (ATIs) have generated important scientific and implementation questions. There is an urgent need to examine challenges navigating the evolving HIV treatment and cure research landscape. From August to October 2022, we conducted 26 semistructured interviews with biomedical researchers and community members representing a predominantly woman demographic to explore the complexity of navigating the rapidly evolving HIV therapeutic and HIV cure research landscape. We purposively sampled individuals recruited from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories for HIV Cure Research. Audio files were transcribed verbatim and analyzed through a thematic approach, using an inductive and iterative process. Among 26 participants, 10 were biomedical researchers and 16 community members, including 11 were people with HIV. Three main themes emerged: (1) We are at a pivotal moment in the evolving landscape of HIV therapeutics and LA HIV treatment and HIV cure research should not be siloed but considered together; (2) There are challenges with engagement in HIV cure research and in switching between oral daily antiretroviral treatment and LA formulations and, mainly, the prolonged pharmacokinetic tail of these compounds matched with limited patient education about their impacts; and (3) There are unique opportunities as a result of this evolving therapeutic landscape, including the key role of decision support for people with HIV, centering around patient autonomy, and the need to learn from the lived experiences of people with HIV who choose LA treatment and/or participation in HIV cure research. Despite a bias toward the woman gender, our study identifies key considerations for navigating concurrent LA HIV treatment and HIV cure research with ATIs from both community members and biomedical researchers' perspectives. Achieving optimal HIV control remains a formidable challenge, necessitating robust interdisciplinary collaborations and engagement with key stakeholders.