Human Immunodeficiency Virus Treatment Research Articles

Virtual avatars as a new tool for human immunodeficiency virus prevention among men who have sex with men: a narrative review.

Human immunodeficiency virus (HIV) continues to affect sexual and gender minorities, predominantly men who have sex with men (MSM). Stigma, medical mistrust, and apprehension towards discussing sexual health with one's medical provider are significant barriers in seeking or accessing preventive services. Those obstacles could be surpassed through novel digital and electronic health interventions, specifically with virtual avatar technology. Avatars are digital self-representative agents that are controlled with an interactive electronic device. Avatars allow for virtual self-immersion within infinitely customizable environments to practice skill building, fostering relationships and more, through an optional incognito approach. The objective of this narrative review is to examine recent uses of and developments in avatar technology, highlight the personalization attribute of this technology, and evaluate its strengths and limitations as a tool for HIV prevention among MSM. We reviewed recent scientific literature generated by PubMed that use virtual avatar technology in HIV prevention and treatment among populations put at risk. Articles that met the inclusion criteria were then categorized on how the avatar technology was used. We identified eleven studies that met inclusion criteria. Avatar technology was found to create a comfortable environment for participants to address and discuss their sexual behaviors with less hesitation. Avatars can build rapport with populations put at high risk, creating an opportunity for reevaluation of their sexual behavior while assisting them in being able seek information, preventive services, or treatment for HIV or other sexually transmitted infections (STIs). Given the increased use of digital technology in health and prevention, avatars might be useful in sexual health education and HIV prevention among populations put at risk. The benefits and potential in utilizing this technology for HIV prevention are highlighted.

Pharmacokinetic Drug-Drug Interactions Involving Antiretroviral Agents: An Update.

Antiretroviral therapy is the recognized treatment for human immunodeficiency virus (HIV) infection involving several antiviral agents. Even though highly active antiretroviral therapy has been proven to be very effective in suppressing HIV replication, the antiretroviral drugs, belonging to different pharmacological classes, present quite complex pharmacokinetic properties such as extensive drug metabolism and transport by membrane-associated drug carriers. Moreover, due to uncomplications or complications in HIV-infected populations, an antiretroviralbased multiple-drug coadministration therapy strategy is usually applied for treatment effect, thus raising the possibility of drug-drug interactions between antiretroviral drugs and common drugs such as opioids, stains, and hormonal contraceptives. Herein, thirteen classical antiretroviral drugs approved by US Food and Drug Administration were summarized. Besides, relative drug metabolism enzymes and transporters known to interact with those antiretroviral drugs were detailed and described. Furthermore, one after the summarized antiretroviral drugs, the drug-drug interactions between two antiretroviral drugs or antiretroviral drug - conventional medical drugs of the past decade were discussed and summarized. This review is intended to deepen the pharmacological understanding of antiretroviral drugs and promote more secure clinical applications for antiretroviral drugs to treat HIV.

Selenium and Omega-3 Fatty Acids Ameliorate Highly Active Anti-Retroviral Therapy (HAART)-induced Reproductive Impairment in Male Wistar Rats.

Highly active anti-retroviral therapy (HAART) is currently the main stay in the treatment of Human Immunodeficiency Virus (HIV) disease. This treatment regimen typically combines three or more antiretroviral drugs and like most drug combinations or polypharmacy, has side effects including those on reproductive function which could place HIV patients on HAART under double risk in terms of reproductive function. Part of tissue damage following HAART administration is blamed on oxidative stress. We therefore sought to explore effects of Omega 3 and Selenium, two common antioxidants on HAART-induced male reproductive impairment in a non-HIV animal model. Sixteen male adult Wistar rats weighing 120g to 250g used for the study were grouped into 4 groups of four rats each (control, HAART-only, HAART + Omega 3 and HAART + Selenium groups). Duration of daily administration was six weeks. Results showed no significant changes in pH of epidydimal semen among the groups. Sperm count and viability were significantly reduced in HAART-only compared with control (p<0.05) but increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p< 0.05). Sperm motility was significantly reduced in HAART-only compared with control group (p< 0.05). A significantly higher percentage of total sperm defects was observed in HAART-only group compared with control (p <0.05) but significantly lower in the HAART + Selenium compared with HAART-only groups (p<0.05). Serum testosterone was significantly reduced in HAART-only compared with control groups (p<0.05) but significantly increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART- only group (p<0.05). Serum concentration of luteinizing and follicle stimulating hormones were not significantly different among the groups. Testicular concentration of malondialdehyde was significantly increased in HAART-only compared with control (p<0.05) but significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p<0.05 in each). Testicular glutathione peroxidase activity was significantly reduced in HAART-only and HAART + Selenium groups compared with control (p< 0.05), but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Testicular superoxide dismutase activity was significantly lower in the HAART-only and HAART + Selenium compared with control (p<0.05) but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Level of tumour necrosis factor - alpha in testes was significantly higher in HAART-only (p<0.05) but lower in the HAART + Selenium (p<0.05) groups compared with control. Tumor necrosis factor-alpha was however significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only (p<0.05 each) groups. Interleukin-6 levels were significantly increased in all HAART-administered groups compared with control (p<0.05 each) though significantly reduced in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). In conclusion, co-administration of Omega 3 or Selenium with HAART ameliorates HAART-induced male reproductive impairment, alteration in redox and inflammatory status in rats. Keywords: HAART, male reproductive impairment, Omega 3, Selenium.

Evaluation of adherence to antiretroviral medications in a supermarket‐based community pharmacy

AbstractIntroductionA critical aspect of human immunodeficiency virus (HIV) infection management and prevention is adherence to antiretroviral (ARV) medications. There are limited recent studies focused on the impact of community pharmacy interventions on ARV adherence; previous studies were conducted between 2004 and 2012 with more complicated regimens.ObjectivesThe primary objective was to compare the adherence rates for ARV medications for both HIV treatment and prevention in patients using HIV‐focused (HIV‐F) pharmacies compared with traditional (non‐HIV focused) pharmacies in a supermarket‐based community pharmacy. The secondary objectives were to determine which factors impact adherence rates as well as the demographic information of patients using HIV‐F pharmacies.MethodsThis was a retrospective study of de‐identified pharmacy dispensing data for patients filling ARV medications from October 2018 to July 2021 at a Safeway pharmacy in the Washington D.C., Maryland, and Virginia (DMV) area. Patients 18 years and older who had fill records at a Safeway pharmacy in the DMV area of at least two 30‐day supplies of ARV medication were included. For all eligible patients, medication adherence was measured by assessing the proportion of days covered (PDC).ResultsOf the 1496 patients who met the inclusion criteria, 971 patients used an HIV‐F pharmacy. Overall, patients were predominantly male (78.9%) with a median age of 44 years. The median PDC score of HIV‐F pharmacies was higher than traditional pharmacies, but the difference was not statistically significant (97.1% vs. 96.6%, respectively, p = 0.2).ConclusionPatients using this regional division supermarket‐based community pharmacy have a high PDC score regardless of pharmacy type. Use of newer ARV agents may have facilitated patients' adherence and diminished the potential benefit of utilizing HIV‐F pharmacies. Pharmacies currently providing specialized patient care for ARV medications may need to re‐evaluate how best to promote medication adherence.

Interruption of Biomedical Interventions Among LGBTQ Individuals in the United States at the Onset of the COVID-19 Pandemic

The COVID-19 pandemic has negatively impacted healthcare access in the United States. This study sought to explore LGBTQ adults’ changes in access and adherence to preexposure prophylaxis (PrEP), human immunodeficiency virus (HIV) treatment, hormone replacement therapy (HRT), and contraception. This study employs data from a cross-sectional internet survey conducted between May and July 2020. The analysis was stratified by medications: PrEP (n = 147), HIV treatment (n = 78), HRT (n = 86), and contraception (n = 185). For people using PrEP, those between the ages of 18–29 and 30–39 and those with insurance did not report having difficulty accessing their medications; however, people between the ages of 30 and 39 did report that they had missed doses of this medication. For people using antiretroviral therapy (ART), cisgender (cis) gay men did not report trouble accessing medications, whereas lesbian cis women, respondents between the ages of 18–29 and 30–39, did report trouble accessing medications. For those using HRT, white non-Hispanic, black, and Latinx individuals did not have trouble accessing medication; however, Asian, Native American, Pacific Islander, and Middle Eastern participants did experience trouble accessing medication. Finally, contraceptive users with insurance did not experience difficulty in accessing medication and did not miss doses of this medication. Changes to medication access and adherence during the COVID-19 pandemic can be used to develop new protocols to help meet the needs of vulnerable populations such as the LGBTQ community. New protocols that may ensure access, as well as privacy around access to medications, are insurance coverage for telehealth.

Development and In-House Validation of an Enzyme-Linked Immunosorbent Assay and a Lateral Flow Immunoassay for the Dosage of Tenofovir in Human Saliva

Highly active antiretroviral therapy (HAART) includes very potent drugs that are often characterized by high toxicity. Tenofovir (TFV) is a widely used drug prescribed mainly for pre-exposure prophylaxis (PreP) and the treatment of human immunodeficiency virus (HIV). The therapeutic range of TFV is narrow, and adverse effects occur with both underdose and overdose. The main factor contributing to therapeutic failure is the improper management of TFV, which may be caused by low compliance or patient variability. An important tool to prevent inappropriate administration is therapeutic drug monitoring (TDM) of compliance-relevant concentrations (ARCs) of TFV. TDM is performed routinely using time-consuming and expensive chromatographic methods coupled with mass spectrometry. Immunoassays, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFIAs), are based on antibody–antigen specific recognition and represent key tools for real-time quantitative and qualitative screening for point-of-care testing (POCT). Since saliva is a non-invasive and non-infectious biological sample, it is well-suited for TDM. However, saliva is expected to have a very low ARC for TFV, so tests with high sensitivity are required. Here, we have developed and validated a highly sensitive ELISA (IC50 1.2 ng/mL, dynamic range 0.4–10 ng/mL) that allows the quantification of TFV in saliva at ARCs and an extremely sensitive LFIA (visual LOD 0.5 ng/mL) that is able to distinguish between optimal and suboptimal ARCs of TFV in untreated saliva.

PrEP Access as HIV Prevention for LGBTQ+ College Students: An Exploration of Current Barriers to Access

Background: Although tremendous strides have been made in Human Immunodeficiency Virus (HIV) prevention, detection, and treatment, HIV remains a public health issue in the United States. Sexual and gender diverse individuals and the 18-24 age group are considered vulnerable populations at risk for contracting the virus. Pre-exposure prophylaxis (PrEP) is a medication that has proven effective in reducing the risk of HIV transmission. Aim: This article aims to justify the necessity of PrEP medication on college campuses, especially for gender and sexual diverse students. Methods: This article provides information on the state of PrEP education, availability, and access on college campuses in the United States. This article also addresses barriers that college students face with accessing PrEP medication through college health services. Results: Limited research has found that most colleges in the United States lack PrEP availability for college students. Other factors, including insurance, privacy concerns, and stigma, may deter students from seeking and taking PrEP medication. Conclusions: This article supports widespread PrEP availability and access on college campuses and acknowledges the need to address barriers that keep students from utilizing PrEP.

Development of dissolving microneedles for intradermal delivery of the long-acting antiretroviral drug bictegravir

Oral administration and intramuscular (IM) injection are commonly recommended options for human immunodeficiency virus (HIV) treatment. However, poor patient compliance due to daily oral dosing, pain at injection sites and the demand for trained healthcare staff for injections limit the success of these administration routes, especially in low-resource settings. To overcome these limitations, for the first time, we propose novel bilayer dissolving microneedles (MNs) for the intradermal delivery of long-acting nanosuspensions of the antiretroviral (ARV) drug bictegravir (BIC) for potential HIV treatment and prevention. The BIC nanosuspensions were prepared using a wet media milling technique on a laboratory scale with a particle size of 358.99 ± 18.53 nm. The drug loading of nanosuspension-loaded MNs and BIC powder-loaded MNs were 1.87 mg/0.5 cm2 and 2.16 mg/0.5 cm2, respectively. Both dissolving MNs exhibited favorable mechanical and insertion ability in the human skin simulant Parafilm® M and excised neonatal porcine skin. Importantly, the pharmacokinetic profiles of Sprague Dawley rats demonstrated that dissolving MNs were able to intradermally deliver 31% of drug loading from nanosuspension-loaded MNs in the form of drug depots. After a single application, both coarse BIC and BIC nanosuspensions achieved sustained release, maintaining plasma concentrations above human therapeutic levels (162 ng/mL) in rats for 4 weeks. These minimally invasive and potentially self-administered MNs could improve patient compliance, providing a promising platform for the delivery of nanoformulated ARVs and resulting in prolonged drug release, particularly for patients in low-resource settings.

Menopause in women living with HIV

Background: Significant improvements in the treatment of human immunodeficiency virus (HIV) have increased the life expectancy of individuals living with HIV to resemble that of the general population. Consequently, a growing number of women living with HIV will reach midlife and go through menopause.

Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial.

Dolutegravir (DTG), combined with a backbone of 2 nucleoside reverse transcriptase inhibitors, is currently the preferred first-line treatment for human immunodeficiency virus (HIV) in childhood. CHAPAS4 is an ongoing randomized controlled trial investigating second-line treatment options for children with HIV. We did a nested pharmacokinetic (PK) substudy within CHAPAS4 to evaluate the DTG exposure in children with HIV taking DTG with food as part of their second-line treatment. Additional consent was required for children on DTG enrolled in the CHAPAS4 trial to participate in this PK substudy. Children weighing 14-19.9 kg took 25 mg DTG as dispersible tablets and children ≥20 kg took 50 mg film-coated tablets. Steady-state 24-hour DTG plasma concentration-time PK profiling was done at t = 0 and 1, 2, 4, 6, 8, 12, and 24 hours after observed DTG intake with food. Reference adult PK data and pediatric data from the ODYSSEY trial were used primarily for comparison. The individual target trough concentration (Ctrough) was defined as 0.32 mg/L. Thirty-nine children on DTG were included in this PK substudy. The geometric mean (GM) area under the concentration-time curve over the dosing interval (AUC0-24h) was 57.1 hours × mg/L (coefficient of variation [CV%], 38.4%), which was approximately 8% below the average AUC0-24h in children in the ODYSSEY trial with comparable dosages, but above the adult reference. The GM (CV%) Ctrough was 0.82 mg/L (63.8%), which was comparable to ODYSSEY and adult reference values. This nested PK substudy shows that the exposure of DTG taken with food in children on second-line treatment is comparable with that of children in the ODYSSEY trial and adult references. Clinical Trials Registration.ISRCTN22964075.

Lived experiences of adolescents living with human immuno- deficiency virus in Namibia

Adolescents living with human immunodeficiency virus (HIV) experience stigma, ill-treatment, and many other challenges due to their health condition. Their experience with HIV is highly overlooked, yet, it shapes their decisions and influences their health outcomes. The objective of this study was to explore and describe the lived experiences of adolescents living with HIV in the Namibian context. We conducted a qualitative study of adolescents (aged 10-19 years) at five different anti-retroviral treatment (ART) clinics in Rundu district, Kavango region Namibia. We used purposive sampling and collected data through in-depth interviews with 21 adolescents from October 2020 to December 2020. We analyzed the data with content analysis. The mean age of participants was 16 years, and the age ranged between 12-19 years. Most participants (62%) have never been in a relationship or engaged in sexual activities. All the participants were in school at the time of the study. The content analysis yielded five broad categories: i) experience with HIV care and treatment, ii) finding out about HIV Status, iii) the interplay between HIV and social relationships, iv) the need for information on HIV and the treatment, v) multiple fears, worries, and means to cope. Adolescents living with HIV (ALWH) experience many challenges due to their health condition. Learning about their HIV status is one of the most challenging experiences. There is a need for continued HIV care and support for adolescents living with HIV, which is adolescent- friendly and focused.

Efficacy and Safety of Two-Drug Regimens That Are Approved from 2018 to 2022 for the Treatment of Human Immunodeficiency Virus (HIV) Disease and Its Opportunistic Infections.

The human immunodeficiency virus (HIV) is a type of virus that targets the body's immune cells. HIV infection can be divided into three phases: acute HIV infection, chronic HIV infection, and acquired immunodeficiency syndrome (AIDS). HIV-infected people are immunosuppressed and at risk of developing opportunistic infections such as pneumonia, tuberculosis, candidiasis, toxoplasmosis, and Salmonella infection. The two types of HIV are known as HIV-1 and HIV-2. HIV-1 is the predominant and more common cause of AIDS worldwide, with an estimated 38 million people living with HIV-1 while an estimated 1 to 2 million people live with HIV-2. No effective cures are currently available for HIV infection. Current treatments emphasise the drug's safety and tolerability, as lifelong management is needed to manage HIV infection. The goal of this review is to study the efficacy and safety of newly approved drugs from 2018 to 2022 for the treatment of HIV by the United States Food and Drug Administration (US-FDA). The drugs included Cabotegravir and Rilpivirine, Fostemsavir, Doravirine, and Ibalizumab. From the review, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) was shown to be noninferior to the continuation of the previous regimen, efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) in virologically suppressed adults with HIV-1. However, DOR/3TC/TDF had shown a preferable safety profile with lower discontinuations due to adverse events (AEs), lower neuropsychiatric AEs, and a preferable lipid profile. Ibalizumab was also safe, well tolerated, and had been proven effective against multiple drug-resistant strains of viruses.

Conjoint tobacco and alcohol use and depression among HIV-positive patients in Sedibeng, South Africa.

Psychosocial challenges among human immunodeficiency virus (HIV)-positive patients may promote substance use disorders. This study explored the relationship between conjoint tobacco and alcohol use and depression symptoms among HIV positive patients in Sedibeng District, South Africa. In a cross-sectional study of 404 participants, a questionnaire collected information on sociodemography, tobacco and alcohol use and depression symptoms. Outcome measures included the prevalence of conjoint tobacco and alcohol use and its association with positive screen for depression. The mean participant age was 43.2 years. Most completed secondary school (62.9%), were black (99.0%), female (65.8%), unemployed (53.6%) and on antiretroviral therapy (ART) for 1 year (97.8%). Current tobacco use was reported by 23.3% (n= 94) participants with most smoking cigarette (73.7%) and having low nicotine dependence (75.5%). Current alcohol use was reported by 43.6% (n= 176) participants, and 36.9% were categorised as harmful users. Only 7.7% (n= 31) participants screened positive for depression; the prevalence of conjoint tobacco and alcohol use was 19.6% (n= 79) and this was not associated with depression (p= 0.438). Harmful alcohol users were more than five times likely to report conjoint tobacco and alcohol use (p= 0.000), but women were less likely to report it (p= 0.000). Conjoint tobacco and alcohol use is common among patients with HIV infection. Although not associated with positive screen for depression, its relationship with harmful alcohol use reiterates the need for an integrated tobacco and alcohol use screening and treatment strategy in the HIV treatment programme in primary care.Contribution:To the authors best knowledge, this study is the first published study that explored the relationship between conjoint tobacco and alcohol use, and depression among HIV-positive patients in the South African primary care settings.

Barriers and facilitators to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review and meta-analysis.

Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing, treatment, and retention to care are low among adolescents. We conducted a mixed-method systematic review to assess anti-retroviral therapy (ART) adherence; barriers and facilitators to ART adherence and ART outcomes among adolescents living with HIV and on ART in sub-Saharan Africa. We conducted searches in four scientific databases for studies conducted between 2010 and March 2022 to identify relevant primary studies. Studies were screened against inclusion criteria and assessed for quality, and data was extracted. Meta-analysis of rates and odd ratios was used to plot the quantitative studies and meta-synthesis summarized the evidence from qualitative studies. A total of 10 431 studies were identified and screened against the inclusion/ exclusion criteria. Sixty-six studies met the inclusion criteria (41 quantitative, 16 qualitative, and 9 mixed-methods study designs). Fifty-three thousand two hundred and seventeen (53 217) adolescents (52 319 in quantitative studies and 899 in qualitative studies) were included in the review. Thirteen support focused interventions for improved ART adherence were identified from quantitative studies. The plotted results from the meta-analysis found an ART adherence rate of 65% (95%CI 56-74), viral load suppression was 55% (95%CI 46-64), un-suppressed viral load rate of 41% (95%CI 32-50), and loss to follow up of 17% (95%CI 10-24) among adolescents. Meta-synthesis found six themes of barriers to ART (social, patient-based, economic, health system-based, therapy-based, and cultural barriers) in both the qualitative and quantitative studies, and three themes of facilitators to ART were also identified (social support, counselling, and ART education and secrecy or confidentiality) from qualitative studies. ART adherence remains low among adolescents in SSA despite multiple interventions implemented to improve ART adherence. The low adherence rate may hinder the attainment of the UNAIDS 2030 targets. Additionally, various barriers to ART adherence due to lack of support have been reported among this age group. However, interventions aimed at improving social support, educating, and counselling adolescents may improve and sustain ART adherence. Systematic review registration: PROSPERO CRD42021284891.

Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ and DOVATO in Healthy Adult Participants.

This randomized food effect study in healthy adult participants examined dispersible tablet formulations of fixed-dose combinations of dolutegravir/abacavir/lamivudine (TRIUMEQ) and dolutegravir/lamivudine (DOVATO). While adult tablet formulations of these combinations are currently approved for the treatment of human immunodeficiency virus, alternate formulations for children are urgently needed to facilitate appropriate pediatric dosing for patients who may have difficulty swallowing a conventional tablet. This study compared the effect of a high-fat, high-calorie meal on the pharmacokinetics, safety, and tolerability of dispersible tablet (DT) formulations of the two-drug and three-drug regimens, with administration under fasting conditions. Both the two-drug and three-drug dispersible tablet formulations, administered under fasting conditions and following a high-fat, high-calorie meal, were well tolerated in healthy participants. There were no clinically relevant differences in drug exposure for either regimen when administered with a high-fat meal as compared to under fasting conditions. Safety observations were similar for both treatments, either in the fed or fasted state. Both TRIUMEQ DT and DOVATO DT formulations can be administer with or without food.

Analysis of inpatient complications in HIV/AIDS patients undergoing total hip arthroplasty – A propensity matched cohort study

Patients with human immunodeficiency virus (HIV) are at higher risk for orthopedic related diseases due to dysregulation in bone metabolism and metabolic effects related to their medication regimen. Furthermore, the rate of hip arthroplasty in HIV patients is increasing. With the recent changes in THA methodologies and improvements in HIV treatment, there is a need for updated research analyzing hip arthroplasty outcomes in this high-risk patient population. In this study, we used a national database to evaluate postoperative outcomes in HIV patients undergoing THA compared to THA patients without HIV. We use a propensity algorithm to create a cohort of 493 HIV negative patients for matched analysis. Among the 367,894 THA patients included in this study, 367,390 patients were HIV negative and 504 were HIV positive. The HIV cohort had a lower mean age (53.34 vs 65.88, p < 0.001), lower proportion of females (44% vs 76.4%, p < 0.001), lower incidence of diabetes without complications (5% vs 11.1%, p < 0.001) and a lower incidence of obesity (0.544 vs 0.875, p = 0.002). In the unmatched analysis, the incidence of acute kidney injury (4.8% vs 2.5%, p = 0.004), pneumonia (1.2% vs 0.2%, p = 0.002), periprosthetic infection (3.6% vs 1%, p < 0.001), and wound dehiscence (0.6% vs 0.1%, p = 0.009) were higher in HIV cohort, most likely due to inherent demographic variances present in the HIV population. In the matched analysis, the rates of blood transfusion (5.0% vs 8.3%, p = 0.041) were lower in the HIV cohort. Other post-operative variables, such as rates of pneumonia, wound dehiscence, and surgical site infections were not statistically significant between the HIV positive population and HIV negative matched cohort. Our study found similar rates of postoperative complications in HIV positive and HIV negative patients. The rate of blood transfusions in HIV positive patients was also noted to be lower. Our data suggests that THA is a safe procedure in patients infected with HIV.

The State of the HIV Epidemic in the Philippines: Progress and Challenges in 2023.

In the past decade, the Philippines has gained notoriety as the country with the fastest-growing human immunodeficiency virus (HIV) epidemic in the Western Pacific region. While the overall trends of HIV incidence and acquired immunodeficiency syndrome (AIDS)-related deaths are declining globally, an increase in new cases was reported to the HIV/AIDS and ART Registry of the Philippines. From 2012 to 2023, there was a 411% increase in daily incidence. Late presentation in care remains a concern, with 29% of new confirmed HIV cases in January 2023 having clinical manifestations of advanced HIV disease at the time of diagnosis. Men having sex with men (MSM) are disproportionately affected. Various steps have been taken to address the HIV epidemic in the country. The Philippine HIV and AIDS Policy Act of 2018 (Republic Act 11166) expanded access to HIV testing and treatment. HIV testing now allows for the screening of minors 15-17 years old without parental consent. Community-based organizations have been instrumental in expanding HIV screening to include self-testing and community-based screening. The Philippines moved from centralized HIV diagnosis confirmation by Western blot to a decentralized rapid HIV diagnostic algorithm (rHIVda). Dolutegravir-based antiretroviral therapy is now the first line. Pre-exposure prophylaxis in the form of emtricitabine-tenofovir disoproxil fumarate has been rolled out. The number of treatment hubs and primary HIV care facilities continues to increase. Despite these efforts, barriers to ending the HIV epidemic remain, including continued stigma, limited harm reduction services for people who inject drugs, sociocultural factors, and political deterrents. HIV RNA quantification and drug resistance testing are not routinely performed due to associated costs. The high burden of tuberculosis and hepatitis B virus co-infection complicate HIV management. CRF_01AE is now the predominant subtype, which has been associated with poorer clinical outcomes and faster CD4 T-cell decline. The HIV epidemic in the Philippines requires a multisectoral approach and calls for sustained political commitment, community involvement, and continued collaboration among various stakeholders. In this article, we outline the current progress and challenges in curbing the HIV epidemic in the Philippines.

Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4+ T Cells.

The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4+ T cells. Histone deacetylases (HDACs) interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4+ T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells.

Estimating the prevalence and correlates of pain among people living with HIV who use unregulated drugs in a Canadian setting.

Although prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and people who use unregulated drugs (PWUD), pain and its possible links to substance use patterns and engagement in HIV treatment remains poorly characterized. We sought to evaluate the prevalence and correlates of pain among a cohort of PLWH who use un-regulated drugs. Between December 2011 and November 2018, 709 participants were recruited, and data were analyzed using generalized linear mixed-effects (GLMM). At baseline, 374 (53 percent) individuals reported moderate-to-extreme pain in the previous 6 months. In a multivariable model, pain was significantly associated with nonmedical prescrip-tion-opioid use (adjusted odds ratio (AOR) = 1.63, 95 percent confidence interval (CI): 1.30-2.05), nonfatal overdose (AOR = 1.46, 95 percent CI: 1.11-1.93), self-managing pain (AOR = 2.25, 95 percent CI: 1.94-2.61), requesting pain medication in the previous 6 months (AOR = 2.01, 95 percent CI: 1.69-2.38), and ever being diagnosed with a mental illness (AOR = 1.47, 95 percent CI: 1.11-1.94). Establishing accessible pain management interventions that address the complex intersection of pain, drug use, and HIV-infection has potential to improve quality of life outcomes among this population.

The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.

Human immunodeficiency virus (HIV) treatment with antiretroviral regimens containing integrase strand transfer inhibitors such as dolutegravir (DTG) and bictegravir (BIC) offers high levels of protection against the development of drug resistance mutations. Despite this, resistance to DTG and BIC can occur through the development of the R263K integrase substitution. Failure with DTG has also been associated with the emergence of the G118R substitution. G118R and R263K are usually found separately but have been reported together in highly treatment-experienced persons who experienced treatment failure with DTG. We used cell-free strand transfer and DNA binding assays and cell-based infectivity, replicative capacity, and resistance assays to characterize the G118R plus R263K combination of integrase mutations. R263K reduced DTG and BIC susceptibility ~2-fold, in agreement with our previous work. Single-cycle infectivity assays showed that G118R and G118R plus R263K conferred ~10-fold resistance to DTG. G118R alone conferred low levels of resistance to BIC (3.9-fold). However, the G118R plus R263K combination conferred high levels of resistance to BIC (33.7-fold), likely precluding the use of BIC after DTG failure with the G118R plus R263K combination. DNA binding, viral infectivity, and replicative capacity of the double mutant were further impaired, compared to single mutants. We propose that impaired fitness helps to explain the scarcity of the G118R plus R263K combination of integrase substitutions in clinical settings and that immunodeficiency likely contributes to its development.