Human Immunodeficiency Virus Treatment Research Articles

Presence of Teen Clubs and its Association with Clinic Attendance among Adolescents Living with HIV in Tanzania: A Retrospective Cohort Study.

Adolescent's living with Human Immunodeficiency Virus (HIV) are widely reported to have poor adherence to antiretroviral therapy (ART) due to stigma and fear of discrimination. A "Teen club" is an adolescent centered intervention designed to reduce social stigma and improve adherence and retention in HIV care. In this study we determined how the availability of teen clubs within routine HIV care and treatment facilities affects adolescents' clinic attendance. We conducted a retrospective cohort study using secondary data from routine clinic records on adolescents (10-19 years) who started ART between 2010 and 2016, and had documented clinic visits between March 2017 and September 2017 at HIV care and treatment clinics (CTC) in northern and central Tanzania. Good clinic attendance was defined as attending at least four monthly clinic visits during the 7-month follow-up period. A Poisson model with robust standard errors was used to assess the relationship between presence of a teen club at health facilities and good clinic attendance adjusting for other factors including sex, age at ART initiation, duration on ART, WHO clinical stage and health facility level. Of the 2839 adolescents, 73.1% had good clinic attendance. Good clinic attendance was independently associated with availability of a teen club at the health facility (aRR=1.16, 95%CI:1.09-1.21) and been on ART for >2 years (aRR=1.15, 95%C1.02-1.30). Adolescents aged 15-19 years during this study were less likely to have good clinic attendance (aRR= 0.93, 95%CI:0.88-0.98) than those aged <15 years. Sex and WHO clinical stage were not associated with good clinic attendance. Teen clubs improved visit adherence among adolescents in HIV care and treatment. Further qualitative research should be conducted to explore adolescents' perception of teen clubs as well as other enablers to clinic attendance.

CNS Prophylaxis Among Patients with HIV-Associated Diffuse Large B-Cell Lymphoma - a Single Center Retrospective Study

Title: CNS Prophylaxis Among Patients with HIV-Associated Diffuse Large B-Cell Lymphoma - A Single Center Retrospective Study Introduction: Patients with Human Immunodeficiency Virus (HIV) are known to develop Lymphoma at a higher rate compared with the general population, with Diffuse Large B-Cell Lymphoma (DLBCL) being the most common subtype. Historically, before the advent of HIV treatment with antiretroviral therapy (ART), HIV-associated DLBCL was considered a more aggressive type of lymphoma and all patients were treated with central nervous system (CNS) prophylaxis. However, since ART has been widely adopted, there is some data to suggest that HIV-associated DLBCL among those taking ART more closely resembles de-novo DLBCL and may not need to be universally treated with CNS prophylaxis. There are no good prospective trials evaluating which patients who develop HIV-associated DLBCL while on ART should receive CNS prophylaxis. Furthermore, studies that tried to predict which DLBCL patients are at greater risk for CNS relapse explicitly excluded patients with HIV. Despite the absence of data, guidelines have shifted and current NCCN guidelines now recommend that HIV patients with DLBCL should be risk stratified as de-novo DLBCL patients with respect to CNS directed therapy. In this study, patients with HIV-associated DLBCL were retrospectively analyzed to understand the patterns of CNS prophylaxis and effects on relapse free survival. Methods: The Electronic Medical Record was queried at a large academic medical center in New York City for patients with HIV-associated DLBCL between the years of 2012 and 2021 using ICD-10 codes. Other subtypes of Lymphoma such as Burkitt's or Plasmablastic Lymphoma were excluded. Patients who did not receive their entire treatment course within the institution were also excluded. Clinical characteristics at diagnosis, treatment type, CNS prophylaxis, and survival data was collected and analyzed. Results: A total of 38 patients were identified according to the inclusion criteria. 26 patients (68%) underwent screening lumbar punctures (LPs) for CNS disease while 12 patients (32%) did not. The two groups were not statistically different within any categories except for LDH, where the LP group had a median LDH of 492 units/L and the non-LP group had a median LDH of 241 units/L (p-value: 0.031). The two groups were not statistically different in cell of origin subtypes, stage, bone marrow involvement, kidney/adrenal involvement, the use of ART prior to diagnosis, IPI or CNS-IPI scores. In addition, among the group that had an LP done with no CNS involvement (n=25), there was no statistical difference in relapse-free survival among those who received adequate CNS prophylaxis and those who did not (p-value 0.886). Conclusions: Among patients with HIV-associated DLBCL in a large academic medical center in New York City, there is no reliable indicator to predict which were offered screening lumbar punctures and which were not. Clinicians may be using additional measures of aggressiveness not accounted for in standard IPI and CNS-IPI scoring algorithms. Furthermore, there was no clear benefit in relapse free survival among high-risk patients who received adequate CNS prophylaxis versus those who did not in this limited sample size. Further research is needed to determine whether patients with HIV-associated DLBCL should be risk stratified similarly to de-novo DLBCL patients with respect to CNS prophylactic therapy.

Spatial heterogeneity in relationship between district patterns of HIV incidence and covariates in Zimbabwe: a multi-scale geographically weighted regression analysis.

A study was conducted to investigate the district-level patterns of incidence of the human immunodeficiency virus (HIV) in Zimbabwe in the period 2005-2015 and explore variations in the relationship between covariates and HIV incidence across different districts. Demographic health survey data were analysed using hotspot analysis, spatial autocorrelation, and multi-scale geographically weighted regression (MGWR) techniques. The analysis revealed hotspots of the HIV epidemic in the southern and western regions of Zimbabwe in contrast to the eastern and northern regions. Specific districts in Matabeleland South and Matabeleland North provinces showed clusters of HIV incidence in 2005-2006, 2010-2011 and 2015. Variables studied were multiple sex partners and sexually transmitted infections (STI) condom use and being married. Recommendations include implementing targeted HIV prevention programmes in identified hotspots, prioritising interventions addressing the factors mentioned above as well as enhancing access to HIV testing and treatment services in high-risk areas, strengthening surveillance systems, and conducting further research to tailor interventions based on contextual factors. The study also emphasizes the need for regular monitoring and evaluation at the district level to inform effective responses to the HIV epidemic over time. By addressing the unique challenges and risk factors in different districts, significant progress can be made in reducing HIV transmission and improving health outcomes in Zimbabwe. These findings should be valuable for policymakers in resource allocation and designing evidence-based interventions.

Machine Learning-Assisted Discovery of Novel Anti-HIV Drug Candidates: An Analysis Using Molecular Datasets

Human Immunodeficiency Virus (HIV) serves as a crisis of global public health, necessitating new anti-HIV agents due to the virus's rapid mutation and subsequent drug resistance. While current Combination Antiretroviral Therapy (CART) has helped control the infection and mortality rates, traditional drug development approaches are costly and inefficient. This study aims to address this issue by applying machine learning algorithms for lead compound discovery using the extensive, quality-assured DTP Antiviral Screen Databases. Three molecular datasets—Extended-Connectivity Fingerprints (ECFP), Simplified Molecular-Input Line-Entry System (SMILES), and 2D molecular IMAGES—were processed using Principal Component Analysis (PCA), train-test splitting, and dataset balancing. Six machine learning algorithms were employed, including linear and nonlinear models, optimized through 5-fold cross-validation. The Area Under the Receiver Operating Characteristic (AUROC) curve was utilized to evaluate the models' performance, as well as the macro averaged precision, averaged recall, averaged F1 score, and balanced accuracy metrics. The ensemble models were constructed from the top-performing individual models. The best individual model, a SVM model trained on the ECFP dataset, achieved performance metrics of 0.78 on macro-averaged precision; 0.68 on macro-averaged recall; 0.72 on macro-averaged F1 score; 0.71 on balanced accuracy; and 0.75 on AUROC when evaluated on the testing data. The best ensemble model, fused with SVM, kNN, and logistic regression trained on the ECFP dataset, achieved performance metrics of 0.82 on macro-averaged precision; 0.67 on macro-averaged recall; 0.72 on macro-averaged F1 score; and 0.70 on balanced accuracy when evaluated on the testing data. The models were then applied to a Pubmed-extracted drug dataset, identifying several promising anti-HIV drug candidates, fulfilling the study's objective to improve the efficiency and success rate of new anti-HIV drug screening and discovery. In summary, this research demonstrates the transformative potential of machine learning in accelerating and optimizing the drug discovery process for HIV treatment.

The Application of Prodrugs as a Tool to Enhance the Properties of Nucleoside Reverse Transcriptase Inhibitors.

Antiretroviral Therapy (ART) is an effective treatment for human immunodeficiency virus (HIV) which has transformed the highly lethal disease, acquired immunodeficiency syndrome (AIDS), into a chronic and manageable condition. However, better methods need to be developed for enhancing patient access and adherence to therapy and for improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS.

FOSAMPRENAVIR CALCIUM LOADED DENDRIMERS: FORMULATION DEVELOPMENT, EVALUATION AND HEMOLYTIC TOXICITY STUDIES

Objective: Dendrimers are the three-dimensional polymeric architectural motif which bestows an advanced platform for drug delivery and drug targeting. Dendrimers are a novel cargo system that can accommodate larger amounts of the drug in its structure by conjugating the drug with terminal amine functional groups. The present work was designed to develop Fosamprenavir calcium-loaded 5th generation poly (propylene imine) (5G PPI) dendrimers for effective treatment of Human immunodeficiency virus. Methods: The drug loading was carried out using a direct method with continuous stirring for 48 h. The sample was characterized using different analytical techniques and also evaluated for drug entrapment, drug release, and release kinetics. The hemolytic toxicity studies were also performed and evaluated based on % hemolysis and surface morphology of RBCs after incubating with the prepared formulation. Results: The Fourier transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectral analysis confirms the conjugation of the Fosamprenavir calcium and dendrimers. Differential scanning calorimetry analysis (DSC) also confirmed the conjugation of the drug with dendrimers. Scanning electron microscopy (SEM) images showcased the spherical floral arrangement of the dendrimer structure. The drug entrapment studies revealed 69.83±0.31% of the drug encapsulated in the dendrimer structure. The drug release studies showed 80.18±0.65% in phosphate buffer pH 7.4 and 68.09±1.78% in acetate buffer pH 5.0. The drug release kinetics showed that the Higuchi release pattern was followed for the release pattern of pH 5 and pH 7.4. The hemolysis study revealed that the conjugation of the drug with 5G PPI dendrimers drastically reduces the hemolysis. Conclusion: Thus, from the studies, it can be concluded that an efficient drug delivery system can be developed for the anti-retroviral drug Fosamprenavir calcium by loading on 5G PPI dendrimers.

Two into one does go: Formulation development of a multipurpose combination vaginal ring releasing dapivirine and metronidazole for prevention of HIV infection and treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection. With the dapivirine-releasing vaginal ring for HIV prevention now approved in several African countries, here we report formulation development of a next-generation ring product that releases both dapivirine (DPV) and the antibiotic drug metronidazole (MET). Following thermal analysis studies to characterize the phase behaviour of DPV-MET mixtures and rheological analysis to assess the cure characteristics of the active silicone elastomer mixes, matrix-type rings were manufactured containing 25 or 200 mg DPV in combination with 100, 250, 500, 1000 or 2000 mg MET. The results for drug content, in vitro release, mechanical testing, and Gardnerella vaginalis time-kill experiments demonstrate the feasibility of incorporating both DPV and MET in a matrix-type ring formulation and indicate that clinically effective release rates may be possible.

Perspectives on HIV pre-exposure prophylaxis (PrEP) implementation in Mississippi among Black women and clinical staff: Recommendations for clinical trauma-informed programs

Intimate partner violence (IPV) can constraint Black women’s ability to prioritize and access Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) services. Recent research has called for the development of trauma-informed PrEP implementation programs to improve the delivery of PrEP to Black cisgender women; however, many PrEP-prescribing settings do not reflect this recommendation. The current study sought to identify key components to develop a trauma-informed PrEP implementation program for Black cisgender women and clinical staff. We conducted focus groups with PrEP-eligible Black cisgender women (February-June 2019), and semi-structured interviews with clinical staff offering HIV prevention and treatment services (October-November 2020) in community healthcare clinics in Mississippi. Seven themes were identified as needed to facilitate integration of trauma-informed approaches into existing PrEP programs, including defining intimate partner violence (IPV), appropriate IPV screening and response, HIV prevention in abusive relationships, staff training needs, and creating supportive clinic environments. PrEP-eligible Black women and clinical staff generally agreed on how to best operationalize IPV screening and response, the importance of trauma-informed staff training, and the need for Black women-specific informational campaigns. However, Black women highlighted the need for providers to discuss HIV prevention in controlling relationships, and to respond to IPV disclosure. HIV pre-exposure prophylaxis has yet to achieve the potential impact observed in trials. Ultimately, realizing the HIV prevention potential of PrEP in the US necessitates centering the perspectives of Black cisgender women and staff to better integrate trauma-informed approaches.

Human Immunodeficiency Virus (HIV) Treatment With Antiretroviral Therapy Mitigates the High Risk of Mental Health Disorders Associated With HIV Infection in the US Population.

Whether treatment of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) is associated with lower risk of mental health disorders (MHDs) among people with HIV (PWH) remains unknown. We aim to determine the association between HIV and MHDs and whether ART alters the risk of MHDs among PWH in the US adult population. We conducted a real-world study using the Merative MarketScan claims database (2016-2020), identifying individuals with HIV (diagnosed using International Classification of Diseases, Tenth Revision, Clinical Modification codes) and those without HIV. A multivariable stratified Cox proportional hazard regression model was conducted to examine the association of HIV treatment status with MHDs, adjusting for potential confounders. Additionally, we sought to determine the effect modification of ART on the relationship between living with HIV and MHDs. A total of 313 539 individuals, with a mean age of 44.2 (standard deviation, 11.4) years, predominantly males (81.2%), residing in the South region of the US (50.9%) were included in the present analysis. During 671 880 person-years of follow-up, 46 235 incident MHD cases occurred. In the multivariable Cox proportional hazard model, living with HIV was associated with higher risk of incident MHDs. Relative to those without HIV, the adjusted hazard ratio was 1.85 (95% confidence interval [CI], 1.79-1.92; P < .001) for those with HIV on treatment, and 2.70 (95% CI, 2.59-2.82; P < .001) for those with HIV without any treatment. Stronger associations between HIV and MHDs were observed in men relative to women, among those aged 18-34 years relative to those aged 55-63 years, and among those with no overweight/obesity relative to obese individuals (Pinteraction < .001 for all). HIV was associated with an increased risk of developing MHDs. However, HIV treatment mitigated the risk.

Increased Levels of Caspase-1 and IL-1β Among Adults With Persistent Immune Activation After 12 Years of Suppressive Antiretroviral Therapy in the Infectious Diseases Institute HIV Treatment Cohort.

We sought evidence of activated pyroptosis and the inflammasome pathways among human immunodeficiency virus (HIV)-infected adults after 12 years of suppressive antiretroviral therapy (ART) and persistent immune activation in the Infectious Diseases Institute HIV treatment cohort in Uganda. In a cross-sectional study, using peripheral blood mononuclear cells of HIV-infected individuals with high and low immune activation (CD4/CD8+CD38+HLA-DR+ cells) relative to HIV-negative reference group, caspase-1 expression was measured using flow cytometry and plasma interleukin 18 and interleukin 1β (IL-1β) levels using enzyme-linked immunosorbent assay. There was higher expression of caspase-1 by CD4 T cells of ART-treated individuals with high immune activation relative to those with lower immune activation (P = .04). Similarly, plasma levels of IL-1β were higher among ART-treated individuals with high immune activation levels relative to those with low immune activation levels (P = .009). We observed a low positive correlation between caspase-1 expression by CD4/CD8 T cells and immune activation levels (r= 0.497 and r= 0.329, respectively). Caspase-1 and IL-1β were high among individuals with high immune activation despite 12 years of suppressive ART. There is a need to further understand the role of persistent abortive infection and the latent HIV reservoir characteristics as drivers of persistent activation and inflammation and to subsequently intervene to prevent the complications of chronic immune activation during long-term ART.

Lived experiences of students with virological failure on antiretrovirals at a university in Limpopo.

Human immunodeficiency virus (HIV)-positive students at a rural university in Limpopo province are followed-up according to the national guidelines for the treatment of HIV. Blood monitoring revealed that some students on antiretroviral (ARV) treatment were not virologically suppressed despite adherence and compliance being emphasised at every visit. The study sought to identify the students' experiences that were hindering the viral load from improving. A two-phase qualitative, explorative, descriptive study design was followed. Convenience purposive sampling methods were taken on. By means of a semi-structured interview guide, face-to-face interviews were directed. Thematic content analysis was applied. Non-disclosure, noisy ARV packaging, stigma, and service delivery played a role in determining levels of student adherence and compliance with ARVs in the study sample. Study findings suggest practical recommendations to improve compliance among students on ARVs: provision of HIV education to all students to help reduce stigma and make it easier to disclose HIV status; use of user-friendly noise-free packaging by pharmaceutical companies to enclose medication, such as blister packs; a supermarket approach in service delivery points to reduce the stigmatising effects of consulting rooms for ARV services.Contribution:There is scope to examine the relevance of these findings for other students in the country, to compare them, and to use material from larger studies to guide targeted interventions that could improve adherence among young people.

Intestinal Microbiota Dysbiosis Promotes Mucosal Barrier Damage and Immune Injury in HIV-Infected Patients

The intestinal microbiota is an “invisible organ” in the human body, with diverse components and complex interactions. Homeostasis of the intestinal microbiota plays a pivotal role in maintaining the normal physiological process and regulating immune homeostasis. By reviewing more than one hundred related studies concerning HIV infection and intestinal microbiota from 2011 to 2023, we found that human immunodeficiency virus (HIV) infection can induce intestinal microbiota dysbiosis, which not only worsens clinical symptoms but also promotes the occurrence of post-sequelae symptoms and comorbidities. In the early stage of HIV infection, the intestinal mucosal barrier is damaged and a persistent inflammatory response is induced. Mucosal barrier damage and immune injury play a pivotal role in promoting the post-sequelae symptoms caused by HIV infection. This review summarizes the relationship between dysbiosis of the intestinal microbiota and mucosal barrier damage during HIV infection and discusses the potential mechanisms of intestinal barrier damage induced by intestinal microbiota dysbiosis and inflammation. Exploring these molecular mechanisms might provide new ideas to improve the efficacy of HIV treatment and reduce the incidence of post-sequelae symptoms.

Loss to Follow-up and Death Among Individuals With Newly Diagnosed Human Immunodeficiency Virus Receiving Dolutegravir-Based First-Line Antiretroviral Treatment in Eastern Ethiopia: Implications for 95% United Nations Targets.

Loss to follow-up (LTFU) and death are unfavorable outcomes of human immunodeficiency virus (HIV) treatment. This study aimed to identify the predictors of LTFU and death among individuals with newly diagnosed HIV receiving dolutegravir (DTG)-based first-line antiretroviral treatment (ART) in eastern Ethiopia. A multisite prospective cohort study was carried out between October 2020 and July 2022. New case patients who started ART were enrolled consecutively and then followed up for the next 6 months. A structured questionnaire and checklists were used to collect data. HIV viral load was determined using the Abbott RealTime HIV-1 assay. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with the outcomes. A total of 235 people with newly diagnosed HIV were enrolled; 16.6% (95% confidence interval, 12.3%-21.9%) were lost to follow-up, and 5.9% (3.5%-9.8%) died within 6 months of follow-up. Baseline World Health Organization clinical stage I (adjusted odds ratio, 3.93 [95% confidence interval, 1.34-11.57]), low viral load (3.67 [1.09-12.36]), and body weight (1.04 [1.01-1.07]) were predictors of LTFU, whereas nonfunctional status (10.02 [1.9-51.3]) was the only factor associated with death. LTFU and death rates among patients with DTG were relatively high, accounting for roughly a quarter of the attrition of people with newly diagnosed HIV from ART care and services. Thus, targeted interventions are required to reduce LTFU and death among individuals with HIV on ART. Further investigation is necessary to evaluate the long-term effects of DTG-based regimens on LTFU and its impact on HIV mortality rates, and qualitative research, specifically tracing LTFU, is recommended.

HivNet: Studying in Depth the Morphology of HIV-1 Virion Using Deep Learning

Purpose: Human Immunodeficiency Virus (HIV) continues to be a disease that kills thousands of individuals each year. The HIV infection is incurable. However, HIV infection has turned into a treatable chronic health condition because of improved access to efficient HIV prevention, diagnosis, treatment, and care. Transmission Electron Microscopy’s (TEM) ability to directly visualize virus particles and distinguish ultrastructure morphology at the nanometer scale, makes it useful in HIV-1 research where it is used for assessing the actions of inhibitors that obstruct the maturation and morphogenesis phases of the virus lifecycle. Hence with its use, the disease's serious stage can be avoided by receiving an early diagnosis.&#x0D; Materials and Methods: Through the dedicated use of computer vision frameworks and machine learning techniques, we have developed an optimized low-computational-cost 8-layer Convolutional Neural Network (CNN) backbone capable of classifying HIV-1 virions at various stages of maturity and morphogenesis. The dataset including TEM images of HIV-1 viral life cycle phases is analysed and augmented through various techniques to make the framework robust in real-time. The CNN layers then extract pertinent disease traits from TEM images and utilise them to provide diagnostic predictions.&#x0D; Results: It was discovered that the framework performed with an accuracy of 99.76% on the training set, 85.83% on the validation set, and 91.33% on the test set, after being trained on a wide range of micrographs which comprised of different experimental samples and magnifications.&#x0D; Conclusion: The suggested network's performance was compared to that of other state-of-the-art networks, and it was discovered that the proposed model was undisputed for classifying TEM images of unseen HIV-1 virion and required less time to train and tweak its weights. The framework can operate more effectively than machine learning algorithms that consume a lot of resources and can be deployed with limited computation and memory resource requirements.

Impact of an Interprofessional HIV Quality Improvement Team on Patient Care and Resident Learning Opportunities.

Although human immunodeficiency virus (HIV) care is a recommended competency for family medicine training, many programs report a lack of HIV expertise among faculty. After the departure of faculty with HIV care experience, an interprofessional HIV quality improvement team (HIV-QIT) of physicians and pharmacists aimed to maintain on-site HIV care and retain learning opportunities for residents, using process improvement and panel reviews with a remote HIV specialist faculty member. This study reports on a multicycle quality improvement pilot project with pre- and postintervention chart reviews between December 2019 and May 2021. All patients received primary care and HIV-QIT chart reviews on-site. We compared patients with integrated HIV care on-site to those receiving external HIV specialty care. Primary outcomes included virologic suppression, CD4 count ≥200 cells/mm3, and adherence to guideline-recommended HIV care. In cycle 1 (January-June 2020), the HIV-QIT reviewed patient charts and sent guideline-based recommendations to physicians. In cycle 2 (July 2020-May 2021), the HIV-QIT implemented several HIV-specific processes, including decision support updates, note templates, order sets, and reference materials. Sustained process improvements included HIV panel chart audits every 3 to 6 months and subsequent provider education. Of 29 patients, more than half (55%, n=16) received integrated HIV care at the primary care site. We found no significant difference in care quality measures between primary and specialty care. Barriers to care completion included missed or canceled follow-up visits, on-site phlebotomy service closures, and declined HIV services. The HIV-QIT maintained on-site HIV treatment and retained experiential learning opportunities through process improvement and specialist-supported care recommendations to primary care physicians.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study

IntroductionThe expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria.MethodsWe analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria’s largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006–2009 as the pre-expansion period and 2010–2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders.ResultsAmong 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01–2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010–2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010–2016 compared to 2006–2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006–2009 and 2010–2016 after adjusting for age, sex, and CD4 T-cell count.ConclusionThe expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study.

Many improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups. This was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer. Seventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8-18) kg vs. 20 (10.5-26) kg, p < 0.0001). Children with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth.

Leveraging CD4 Cell Count at Entry Into Care to Monitor Success of Human Immunodeficiency Virus Prevention, Treatment, and Public Health Programming in the Greater St Louis Area Between 2017 and 2020.

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

Acute HIV Diagnosis After Initiation of Pre-exposure Prophylaxis in a Young Adult Patient: A Case Report

Oral pre-exposure prophylaxis (PrEP) in the prevention of human immunodeficiency virus (HIV) infection is highly effective, yet the majority of sexually active adolescents and young adults (AYAs) at highest risk for HIV infection, particularly AYA males who have sex with males, have not been prescribed this medication. Provider hesitancy in prescribing PrEP to at-risk AYA patients is often associated with concerns about patient nonadherence and its effect on inducing HIV medication resistance. This case report has two aims. First, to outline the clinical course for an AYA patient prescribed PrEP for 3 months and then found to have HIV with an M184V resistance mutation and subsequently started on HIV treatment. And second, to illustrate how the benefits of PrEP initiation outweigh its risks by presenting clinical data on resistance patterns to PrEP medications. The patient eventually achieved viral suppression within 5 months of starting HIV treatment which has been sustained up to 2 years. This case illustrates that M184V resistance mutations, although rarely associated with PrEP, are unlikely to impact options for HIV treatment. Providers should recommend and prescribe oral PrEP to AYA patients at risk for HIV infection without concern for nonadherence leading to HIV medication resistance.