Antiretroviral Research Articles

Do women with HIV, diabetes mellitus, and full antiretroviral therapy adherence have a lower rate of HIV viremia than men?

Do women with HIV, diabetes mellitus, and full antiretroviral therapy adherence have a lower rate of HIV viremia than men?

Current Trends in HIV Infection in the Republic of Crimea

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection.

Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV). Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI. Results: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S. Conclusions: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.

Characterising HIV-Indicator conditions among two nationwide long-term cohorts of people living with HIV in Germany (1999-2023).

Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive. Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999-2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30days) and HIV-transmission routes were collected. In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29-40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17-20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20-24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29-32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350. This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients' immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation.

Effectiveness, safety, and patient-reported outcomes of emtricitabine/tenofovir alafenamide-based regimens for the treatment of HIV-1 infection: Final 24-month results from the prospective German TAFNES cohort study.

Tenofovir alafenamide (TAF) was introduced in the European Union in 2015 as a novel prodrug of tenofovir showing similar efficacy in clinical trials and a more favorable safety profile than tenofovir disoproxil fumarate (TDF). The German TAFNES cohort study (2016-2019) was conducted to generate real-world evidence. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (PWH) receiving elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF), rilpivirine/F/TAF (R/F/TAF) or F/TAF + 3rd agent were included. Month (M) 24 outcomes included virologic effectiveness (HIV RNA <50 copies/mL), treatment persistence, adverse drug reactions (ADRs) and patient-reported outcomes, using the HIV Symptom Index (HIV-SI), 36-Item Short Form Health Survey (SF-36) and HIV Treatment Satisfaction (HIVTSQ) questionnaires. The study included 767 PWH (92% men, median age 46 years; 301 TN, 466 TE; E/C/F/TAF [n = 318], R/F/TAF [n = 192], F/TAF + 3rd agent [n = 257]). Among TN, 35% had late HIV diagnosis (CD4 < 350/μL and/or AIDS). Of TE, 95% were on suppressive antiretroviral therapy (ART) before switching. D:A:D (Data Collection on Adverse Effects of Anti-HIV Drugs) 5-year risks for chronic kidney disease were high for about 1 in 10 TN and 4 in 10 TE. Overall treatment persistence at M24 was 81% (E/C/F/TAF: 88%; R/F/TAF: 86%; F/TAF + 3rd agent: 70%, with ART simplification of multiple-tablet regimens in 13%). M24 viral suppression (missing = excluded) was 96% (479/501). Discontinuations due to virologic failure or ADRs were rare, 2% (12/767) and 4% (30/767), respectively. HIV-SI and SF-36 summary scores improved in TN; HIVTSQ change scores showed an improvement in treatment satisfaction in TE. Real-world data confirmed a favorable safety profile and high virologic effectiveness with high treatment satisfaction on F/TAF-based ART.

Evaluation of risk factors for obesity among HIV positive adults on antiretroviral therapy in Delta State, Nigeria

Evaluation of risk factors for obesity among HIV positive adults on antiretroviral therapy in Delta State, Nigeria

Archived HIV-1 Drug Resistance Mutations: Role of Proviral HIV-1 DNA Genotype for the Management of Virological Responder People Living with HIV

Despite its effectiveness in controlling plasma viremia, antiretroviral therapy (ART) cannot target proviral DNA, which remains an obstacle to HIV-1 eradication. When treatment is interrupted, the reservoirs can act as a source of viral rebound, highlighting the value of proviral DNA as an additional source of information on an individual’s overall resistance burden. In cases where the viral load is too low for successful HIV-1 RNA genotyping, HIV-1 DNA can help identify resistance mutations in treated individuals. The absence of treatment history, the need to adjust ART despite undetectable viremia, or the presence of LLV further support the use of genotypic resistance tests (GRTs) on HIV-1 DNA. Conventionally, GRTs have been achieved through Sanger sequencing, but the advances in NGS are leading to an increase in its use, allowing the detection of minority variants present in less than 20% of the viral population. The clinical significance of these mutations remains under debate, with interpretations varying based on context. Additionally, proviral DNA is subject to APOBEC3-induced hypermutation, which can lead to defective, nonviable viral genomes, a factor that must be considered when performing GRTs on HIV-1 DNA.

Development of KSHV vaccine platforms and chimeric MHV68-K-K8.1 glycoprotein for evaluating the in vivo immunogenicity and efficacy of KSHV vaccine candidates.

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 is an etiological agent of Kaposi's Sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Considering the high seroprevalence reaching up to 80% in sub-Saharan Africa, an effective vaccine is crucial for preventing KSHV infection. However, vaccine development has been limited due to the lack of an effective animal model that supports KSHV infection. Murine Herpesvirus 68 (MHV68), a natural mouse pathogen persisting lifelong post-infection, presents a promising model for KSHV infection. In this study, we developed KSHV vaccine and a chimeric MHV68 carrying the KSHV glycoprotein, serving as a surrogate challenge virus for testing KSHV vaccines in a mouse model. Among KSHV virion glycoproteins, K8.1 is the most abundant envelope glycoprotein with the highest immunogenicity. We developed two K8.1 vaccines: K8.1 mRNA-lipid nanoparticle (LNP) vaccine and K8.126-87-Ferritin (FT) nanoparticle vaccines. Both induced humoral responses in immunized mice, whereas K8.1 mRNA LNP also induced T cell responses. Using BACmid-mediated homologous recombination, the MHV68 M7 (gp150) gene was replaced with KSHV K8.1 gene to generate chimeric MHV68-K-K8.1. MHV68-K-K8.1 established acute and latent infection in the lungs and spleens of infected mice, respectively. Mice immunized with K8.1 mRNA LNP or K8.126-87-FT showed a reduction of MHV68-K-K8.1 titer but not MHV68 wild type (WT) titer in the lung. In addition, viral reactivation of MHV68-K-K8.1 was also significantly reduced in K8.1 mRNA LNP-immunized mice. This study demonstrates the effectiveness of two vaccine candidates in providing immunity against KSHV K8.1 and introduces a surrogate MHV68 system for evaluating vaccine efficacy in vivo.IMPORTANCEKaposi's sarcoma-associated herpesvirus (KSHV) is a prevalent virus that establishes lifelong persistent infection in humans and is linked to several malignancies. While antiretroviral therapy has reduced Kaposi's Sarcoma (KS) complications in people with HIV, KS still affects individuals with well-controlled HIV, older men without HIV, and transplant recipients. Despite its significant impact on human health, however, research on KSHV vaccine has been limited, mainly due to the lack of interest and the absence of a suitable animal model. This study addresses these challenges by developing KSHV K8.1 vaccine with two platforms, mRNA lipid nanoparticle (LNP) and FT nanoparticle. Additionally, chimeric virus, MHV68-K-K8.1, was created to evaluate KSHV vaccine efficacy in vivo. Vaccination of K8.1 mRNA LNP or K8.126-87-FT significantly reduced MHV68-K-K8.1 titers. Developing an effective KSHV vaccine requires an innovative approach to ensure safety and efficacy, especially for the immunocompromised population and people with limited healthcare resources. This study could be a potential blueprint for future KSHV vaccine development.

Determination and Quantification of Related Impurity Substances in Elvitegravir Drug Substance by Full Factorial Design Evaluated Liquid Chromatography Method

ABSTRACTHerein, our work deals with developing a rapid, accurate, and reliable high‐performance liquid chromatographic technique with the application of quality by design (QbD) experimental tool to quantify Elvitegravir drug (Integrase inhibitors of antiretroviral drug) and its novel related impurities at low levels. Further, this unique method has been validated to prove its consistency. Separation of N‐methyl Elvitegravir (Impurity‐I), 2‐fluoro Elvitegravir (Impurity‐II), and Elvitegravir isopropyl ester (Impurity‐III) in Elvitegravir drug substance was executed by using Kinetex C18 column (150 mm × 2.1 mm × 1.7 µm) with water, acetonitrile, formic acid, and triethylamine (690:300:6:2, v/v/v/v/), mobile phase (MB‐A) and acetonitrile, formic acid and triethylamine (990:6:2, v/v/v), MB‐B. This developed analytical technique gave a well‐separated peak at the retention times of 9.126 min (Elvitegravir), 7.713 min (Impurity‐I), 7.972 min (Impurity‐II), and 8.548 min (Impurity‐III) adequate with the peak properties as per the United States Pharmacopeia guideline. The method's sensitivity and linearity are established by its detection and quantification limits at low levels with a correlation coefficient of 0.998. The method's repeatability, specificity, and accuracy suggest that this developed technique is a reliable determination strategy for Elvitegravir drug substance and its related impurities (Impurity‐I, Impurity‐II, and Impurity‐III) in a simple, feasible, and affordable way.

ФАРМАКОЭКОНОМИЧЕСКИЕ ПОДХОДЫ К АНАЛИЗУ СТОИМОСТИ АНТИРЕТРОВИРУСНЫХ ПРЕПАРАТОВ, ПРИМЕНЯЕМЫЕ В ТЕРАПИИ ВИЧ-ИНФИЦИРОВАННЫХ ПАЦИЕНТОВ

The legislation in force in the Russian Federation guarantees HIV patients protection of their rights in labor, education and other spheres of life, as well as free counseling, diagnosis and treatment of HIV infection. The continued increase in the number of infected people and, more importantly, the emergence of the HIV epidemic from risk groups into the general population highlights the need for additional improvement in the effectiveness of measures taken to counter the spread of infection. In this regard, it is necessary to use the most rational measures, both from the point of view of efficiency and safety, and from the point of view of costs. The most suitable tool for solving these problems is pharmacoeconomical analysis. At the same time, conducting pharmacoeconomical analysis in the field of HIV infection, as well as in any other nosology, involves the need to take into account certain features at the stages of planning and implementation of the study. It is necessary to highlight some key features of the methodology of pharmacoeconomical analysis in the assessment of healthcare technologies in the field of HIV infection, in particular, cost minimization analysis, which involves choosing a medical technology with minimal costs by comparing the monetary value of alternative technologies, provided the same therapeutic effectiveness. The main object of the study was the documented medical histories of HIV-infected patients, statistical and analytical methods of analysis were used and it was established that in the Russian Federation and in Kuzbass there are all drugs for the treatment of patients with HIV infection included in modern lists of treatment standards according to clinical recommendations. The difference in the cost of antiretroviral drugs at the price of government funding has been established, which affects the costs of treating HIV-infected patients.

Causes and Consequences of Persistent Anemia after 6 Months of Antiretroviral Therapy in Tanzania: An Observational Comparative Cohort Study.

Anemia is common among people living with HIV (PLWH), particularly in Africa. Outcomes for PLWH on modern antiretroviral therapy (ART) regimens are not well documented. We conducted an observational study to determine the outcomes and predictors of anemia after ART initiation in Tanzania. We enrolled and followed ART-naïve PLWH and HIV-uninfected individuals at three clinics in Tanzania. We grouped participants into four longitudinal categories based on hemoglobin concentration measured at baseline and 6 months after ART initiation (normal, resolved anemia, incident anemia, and persistent anemia) and followed them for 24 months. There were 991 study participants (494 PLWH, 497 HIV uninfected). After 6 months of ART, 33.9% of PLWH had persistent anemia and 9.9% had incident anemia compared with 12.6% and 9.6% for HIV-uninfected controls. Female sex (adjusted odds ratio [aOR]: 2.62; 95% CI: 1.91-6.75) and low income (aOR: 3.10; 95% CI: 1.36-7.20) were strong predictors of persistent anemia for both PLWH and HIV-uninfected individuals. For PLWH, having a CD4+ T cell count of less than 350 cells/mm3 (aOR: 0.34; 95% Cl: 0.15-0.73) was significantly associated with anemia resolution. Mortality was higher for PLWH who had persistent anemia or incident anemia than for PLWH who had normal hemoglobin or improved anemia (hazard ratio: 4.0, 95% Cl 1.3-12.2). One-third of adults in Tanzania had persistent anemia after 6 months on ART, and persistent anemia was associated with increased mortality. PLWH with persistent or incident anemia after 6 months on modern ART deserve close follow-up, particularly women and low-income adults.

Current Nanotechnological Strategies for Delivery of Anti-Retroviral Drugs: Overview and Future Prospects

Abstract: Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservoirs are responsible for persistent infection. Elimination of the virus from these reservoirs is critical for successful long-term therapy. Therefore, innovative approaches are required to design safe and effective therapies. Nanotechnology has revolutionized HIV drug delivery by addressing key challenges, including improving drug solubility, targeting specific cells, extending drug release, protecting drugs from degradation, overcoming biological barriers, enabling combination therapy, and enhancing vaccine delivery. Several nanocarrier systems, such as dendrimers, nanoemulsions, liposomes, solid nanoparticles (SLNs), and nanostructured lipid carriers, have been proposed to treat HIV infection. Additionally, nanosuspensions of antiretroviral drugs offer promising strategies for improving treatment outcomes. While these advancements have significantly improved HIV management strategies, challenges remain, including unexpected toxicity, avoiding harmful biological interactions, and costs associated with the large-scale production of nanopharmaceuticals.

Successful Management of Progressive Multifocal Leukoencephalopathy in an HIV/AIDS Patient: A Therapeutic Case Report

Background: Progressive multifocal leukoencephalopathy (PML), a rare and devastating opportunistic infection caused by JC virus reactivation, typically carries a poor prognosis in immunocompromised individuals, particularly those with HIV. Aim: To report a remarkable case of full recovery in an HIV-positive patient with PML and highlight the significance of prompt recognition, diagnosis, and combination antiretroviral therapy (cART). Case Summary: A 34-year-old HIV-positive male presented with progressive disturbances of consciousness and movement. MRI revealed multifocal white matter lesions, and JC virus DNA was detected in cerebrospinal fluid. Despite initial deterioration, the patient achieved full recovery with cART. Conclusion: This exceptional outcome emphasizes the critical importance of vigilant monitoring, prompt diagnosis, and effective management strategies for PML in HIV patients, highlighting the potential for full recovery with optimal cART.

Evaluation of Right Ventricular Diastolic Function among HIV-1-Infected Patients on Highly Active Antiretroviral Therapy and its Relationship with CD4 Cell Count and Viral Load

Abstract Context: With the introduction of highly active antiretroviral therapy, human immunodeficiency virus (HIV) patients live longer and therefore develop complications such as cardiovascular diseases. The prevalence of left ventricular diastolic dysfunction among HIV-infected patients ranges from 2.7% to 64%. Data on right ventricular diastolic function among HIV-infected patients in our region of northeastern Nigeria are lacking. Aims: We therefore assessed right ventricular diastolic function among HIV-infected patients on highly active antiretroviral therapy (HAART). Materials and Methods: This cross-sectional study was conducted among HIV-infected patients receiving HAART at the Federal Medical Centre Nguru, Yobe State, Northeastern Nigeria. Tricuspid flow E/A ratio, right ventricular deceleration time, and tissue Doppler E/e’ waves were used to assess the right ventricular diastolic function. Results: One hundred and seven subjects were recruited into the study comprising 70 (65.4%) females and 37 (34.6%) males. The prevalence of right ventricular diastolic dysfunction is 12.15%. CD4 cell count correlated positively with right ventricular deceleration time and negatively with tricuspid E/A ratio. Viral load correlated positively with the tricuspid E/A ratio and negatively with the tricuspid E/e ratio and right ventricular deceleration time. Conclusion: Right ventricular diastolic dysfunction is not uncommon among HIV-infected patients in northeastern Nigeria; its prevalence was found to be 12.15%, and there was a significant positive correlation between right ventricular deceleration time and CD4 cell count and a significant negative correlation between right ventricular deceleration time and viral load, suggesting that lower CD4 cell count and higher viral load are associated with worsening right ventricular diastolic function.

Cardiac biomarkers can detect and track subclinical HIV-associated myocardial disease in newly diagnosed people living with HIV

Abstract Background Cardiovascular disease (CVD) in people living with HIV (PLWH) remains poorly understood, and the profile of disease differs between high-income and low- and middle-income settings[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD[2]. Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. Purpose To assess the presence and evolution of subclinical myocardial disease, we prospectively assessed the hearts of newly diagnosed PLWH and matched, HIV-uninfected controls using cardiac biomarkers and correlated our findings with cardiovascular magnetic resonance imaging (CMR). Methods Newly diagnosed, antiretroviral treatment (ART) naïve PLWH were recruited along with HIV uninfected, age- and sex-matched controls in the Western Cape Province of South Africa. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), Galectin-3, and a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in, and between groups. Results Compared with controls (n=22), hs-cTnT (4.0 ng/l vs 5.1 ng/l; p=0.004) , NT-proBNP (23.2 ng/l vs 40.8 ng/l; p=0.02), and Galectin-3 (6.8 ng/ml vs 9.0 ng/ml; p=0.002) were all significantly higher in the ART naïve group (n=73). After 9 months of ART, hs-cTnT (5.1 ng/l vs 4.3 ng/l; p=0.02) and NT-proBNP (40.8 ng/l vs 28.5 ng/l; p=0.03) both decreased significantly, and a trend of decrease was seen in sST2 (16.5 ng/ml vs 14.8 ng/l; p=0.08). Galectin-3 did not demonstrate decrease over time (9.0 ng/ml vs 8.8 ng/ml; p=0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and ECV, were NT-proBNP (rs≥0.4, p&amp;lt;0.001) and Galectin-3 (rs≥0.3, p&amp;lt;0.01). Conclusion Our cardiac biomarker data supports the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The elevation of Galectin-3 despite ART may be indicative of ongoing cardiac remodelling that may incur future risk of CVD, and necessitates further study. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR, showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Severity and Number of Substances Used are Independently Associated with Antiretroviral Therapy Adherence Over Time among People with HIV in the Current Treatment Era.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.

Reduction of aortic stiffness in newly diagnosed persons with HIV-infection: modifiable vascular dysfunction after antiretroviral therapy?

Abstract Background People living with HIV (PLWH) are at an increased risk of cardiovascular disease (CVD), which is underestimated by contemporary risk stratification systems[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD. Aortic stiffness, as measured with pulse wave velocity (PWV), is a validated predictor of CVD [2,3] and has been shown to be elevated in PLWH at the time of HIV diagnosis compared to HIV-uninfected persons[4]. Purpose To prospectively assess the influence of contemporary antiretroviral therapy (ART) on aortic stiffness in a group of newly diagnosed PLWH in a low- to middle-income setting. Methods A group of ART naïve PLWH with modest cardiovascular risk and free from known CVD, was recruited at the time of HIV diagnosis from the Western Cape Province of South Africa. Aortic stiffness was measured using carotid-femoral PWV on a commercially available device that simultaneously measured the carotid and femoral waveforms on a supine patient in a temperature-controlled room utilising established methodology[4]. The algorithmically-calculated time delay between the upstroke of the carotid and femoral wave-forms provided the transit time (TT). Carotid femoral path distance (path length) was measured using surface anatomy. PWV was calculated as direct path length divided by TT. Aortic distensibility was expressed according to the Bramwell-Hill equation as 3.57/PWV(squared)[5]. ART was initiated and PWV was re-evaluated 9 months later. Results Seventy-three participants completed follow-up and were included. The cohort was relatively young (mean age 32±7 years) with good female representation (n=33, 45%). Most received tenofovir/lamivudine/dolutegravir (n=71, 97%) Half of the group smoked cigarettes. Two participants were controlled hypertensives, and two participants had metabolic syndrome. A significant decrease in PWV (with scaling factor of 0.8) was observed at 9 months of ART (5.93 ±1.0 vs. 5.69 ±1.0 m/s; p=0.01). Aortic distensibility increased significantly as well (0.20 [IQR: 0.16 to 0.26] vs. 0.21 [IQR: 0.19 to 0.27] mmHg-1; p=0.02). Conclusion Improvement in aortic stiffness was observed in a group of newly diagnosed PLWH after 9 months of ART-initiation. This provides evidence of a modifiable component of vascular dysfunction and, in turn, cardiovascular risk with the use of contemporary ART at 9 months. It is unknown if this effect will be sustained long-term. The use of aortic stiffness (alone or in combination with other parameters) as a predictor of cardiovascular outcomes in the ART era requires further study.Abstract figureAbstract table

Time to viral load suppression and its predictors among people living with HIV on antiretroviral therapy in Gebi Resu zone, Afar Region, Ethiopia, 2023.

This study aimed to estimate the time to viral load suppression and identify its predictors among HIV patients receiving antiretroviral therapy (ART) in the Gebi Resu zone, Afar Region, Ethiopia, 2023. The study was conducted at public health facilities in the Gebi Resu zone of the Afar region. This study is a facility-based, retrospective follow-up study. This study included 298 people living with HIV who were receiving ART services at selected health facilities in the Gebi Resu zone. Data were collected by reviewing patient records using a structured checklist. Bivariate and multivariate Cox regression analyses were conducted to assess the relationship between variables and control for confounders. The incidence rate of viral load suppression was 9.46 per 100 person-months. The median time to viral load suppression was 7.7 months, with an interquartile range of 3.8 months (IQR = 6.47-10.27). Patients at clinical stages 3 and 4 [AHR = 0.67, 95%CI (0.47, 0.96)], those who received cotrimoxazole prophylaxis therapy [AHR = 1.47, 95%CI (1.12, 1.92)], and patients with poor drug adherence [AHR = 0.40, 95%CI (0.18, 0.90)] were significantly associated with time to viral load suppression among people on antiretroviral therapy. The time to viral load suppression and the median time to viral load suppression among people living with HIV on ART were shorter than those observed in many developing and developed countries. Clinical stage, cotrimoxazole prophylaxis therapy, and drug adherence were significant predictors of viral load suppression.

REverse transcriptase ACTivity (REACT) assay for point-of-care measurement of established and emerging antiretrovirals for HIV treatment and prevention.

Maintaining adequate levels of antiretroviral (ARV) medications is crucial for the efficacy of HIV treatment and prevention regimens. Monitoring ARV levels can predict or prevent adverse health outcomes like treatment failure or drug resistance. However, conventional ARV measurement using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is slow, expensive, and centralized delaying clinical and behavioral interventions. We previously developed a rapid enzymatic assay for measuring nucleotide reverse transcriptase inhibitors (NRTIs) - the backbone of HIV treatment and prevention regimens - based on the drugs' termination of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we expand our work to include non-nucleoside reverse transcriptase inhibitors (NNRTIs) - an ARV class used in established and emerging HIV treatment and prevention regimens. We demonstrate that the REverse Transcriptase ACTivity (REACT) assay can detect NNRTIs including medications used in oral and long-acting/extended-release HIV treatment and prevention. We demonstrate that REACT can measure NNRTIs spiked in either buffer or diluted plasma and that fluorescence can be measured on both a traditional plate reader and an inexpensive portable reader that can be deployed in point-of-care (POC) settings. REACT measured clinically relevant concentrations of five NNRTIs spiked in aqueous buffer. REACT measurements showed excellent agreement between the plate reader and the portable reader, with a high correlation in both aqueous buffer (Pearson's r = 0.9807, P < 0.0001) and diluted plasma (Pearson's r = 0.9681, P < 0.0001). REACT has the potential to provide rapid measurement of NNRTIs in POC settings and may help to improve HIV treatment and prevention outcomes.

Impact of Dolutegravir plus Lamivudine as First-Line Antiretroviral Treatment on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood.

To compare the effects of first-line antiretroviral treatment (ART) with dolutegravir plus lamivudine (DTG+3TC) versus DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) on the evolution of the HIV-1 reservoir and immune activation biomarkers in people with HIV (PWH). DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naïve PWH. Participants were randomized (1:1) to receive ART with DTG+3TC (2DR group) or DTG+FTC/TAF (3DR group). Total and intact proviral HIV-1 DNA, cell-associated RNA in CD4+ T cells, the frequency of HIV-infected CD4+ T cells able to produce p24, plasma soluble inflammatory markers (IL-6, sCD14, TRAIL, IP-10, FABP2, CRP and D-dimer), and activation and exhaustion markers in CD4+ and CD8+ T cells were longitudinally determined. Forty-four participants (22 per study arm) were enrolled. Baseline mean (SD) log10 plasma viral load (pVL) and CD4+ T cell counts were 4.4 (0.7) copies/mL and 493 (221) cells/mm3, respectively. All participants completing the study (2DR n=20; 3DR n=21) had pVL <50 copies/mL at week 48, except for one in the 2DR group who was resuppressed after treating syphilis. Changes from baseline to week 48 in all reservoir parameters or in levels of soluble inflammatory biomarkers and activated or exhausted CD4+ and CD8+ T cells were similar between 2DR and 3DR groups. First-line ART with DTG+3TC resulted in a similar reduction of HIV-1 persistence parameters in peripheral blood, and comparable changes in immune-associated soluble and T-cell markers compared with DTG+FTC/TAF. These findings support recommendation of DTG/3TC among preferred options for first-line ART in PWH.