Search

Introduction: Antiretroviral (ARV) drugs have improved prognoses for people living with HIV. However, HIV-associated neurocognitive disorders (HAND) persist despite undetectable viral loads. Some ARVs have been linked to neuropsychiatric effects that may contribute to HAND. Synapse loss correlates with cognitive decline in HAND and synaptic deficits may contribute to the neuropsychiatric effects of ARV drugs. Methods: Using an automated high content assay, rat hippocampal neurons in culture expressing PSD95-eGFP to label glutamatergic synapses and mCherry to fill neuronal structures were imaged before and after treatment with 25 clinically used ARVs. Results and Discussion: At a concentration of 10 µM the protease inhibitors nelfinavir and saquinavir, the non-nucleoside reverse transcriptase inhibitors etravirine and the 8-OH metabolite of efavirenz, the integrase inhibitor bictegravir, and the capsid inhibitor lenacapavir produced synaptic toxicity. Only lenacapavir produced synapse loss at the nanomolar concentrations estimated free in the plasma, although all 4 ARV drugs induced synapse loss at Cmax. Evaluation of combination therapies did not reveal synergistic synaptic toxicity. Synapse loss developed fully by 24 h and persisted for at least 3 days. Bictegravir-induced synapse loss required activation of voltage-gated Ca2+ channels and bictegravir, etravirine, and lenacapavir produced synapse loss by an excitotoxic mechanism. These results indicate that select ARV drugs might contribute to neuropsychiatric effects in combination with drugs that bind serum proteins or in disease states in which synaptic function is altered. The high content imaging assay used here provides an efficient means to evaluate new drugs and drug combinations for potential CNS toxicity. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV) infection causes Acquired Immune Deficiency Syndrome (AIDS), a collection of symptoms arising from the deteriorating immunity. The number of people living with HIV worldwide continues to increase year-by-year. Those infected with HIV need antiretroviral (ARV) therapy to suppress the amount of HIV in the body. Purpose: This study aimed to investigate the determinants of adherence in people living with HIV/AIDS (PLHIV) undergoing ARV therapy in Situbondo Regency. Methods: This study employed a quantitative analytic observational approach with a cross-sectional design. Data analysis involved both descriptive and multivariate analysis. The population for this study consisted of 328 individuals, from which 212 were selected as samples, all being PLHIV on ART as of April 2022, sourced from ARV treatment services in Situbondo district. Results: The research analysis was based on predisposing factors, measured using three indicators: work, knowledge, and belief in ARVs. Supporting aspects were measured by two factors: ownership of health insurance and adherence counselling. Reinforcing factors were measured using two indicators: family support and stigma in the community. Conclusion: The study concluded that predisposing and reinforcing factors significantly influenced PLHIV adherence to antiretroviral therapy. However, supporting factors did not show a significant influence on adherence in PLHIV undergoing antiretroviral therapy in the Situbondo District.

Introduction: Antiretroviral (ARV) drugs have improved prognoses for people living with HIV. However, HIV-associated neurocognitive disorders (HAND) persist despite undetectable viral loads. Some ARVs have been linked to neuropsychiatric effects that may contribute to HAND. Synapse loss correlates with cognitive decline in HAND and synaptic deficits may contribute to the neuropsychiatric effects of ARV drugs.Methods: Using an automated high content assay, rat hippocampal neurons in culture expressing PSD95-eGFP to label glutamatergic synapses and mCherry to fill neuronal structures were imaged before and after treatment with 25 clinically used ARVs.Results and Discussion: At a concentration of 10 μM the protease inhibitors nelfinavir and saquinavir, the non-nucleoside reverse transcriptase inhibitors etravirine and the 8-OH metabolite of efavirenz, the integrase inhibitor bictegravir, and the capsid inhibitor lenacapavir produced synaptic toxicity. Only lenacapavir produced synapse loss at the nanomolar concentrations estimated free in the plasma, although all 4 ARV drugs induced synapse loss at Cmax. Evaluation of combination therapies did not reveal synergistic synaptic toxicity. Synapse loss developed fully by 24 h and persisted for at least 3 days. Bictegravir-induced synapse loss required activation of voltage-gated Ca2+ channels and bictegravir, etravirine, and lenacapavir produced synapse loss by an excitotoxic mechanism. These results indicate that select ARV drugs might contribute to neuropsychiatric effects in combination with drugs that bind serum proteins or in disease states in which synaptic function is altered. The high content imaging assay used here provides an efficient means to evaluate new drugs and drug combinations for potential CNS toxicity.

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-g expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound. [ABSTRACT FROM AUTHOR]

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound.

Introduction: Behavioral risk factors, in addition to increasing the risk of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) transmission, can affect antiretroviral therapy (ART) compliance of people with the condition. The aim of this study was to determine the prevalence of behavioral risk factors and its' effect on adherence to antiretroviral drugs (ARV) treatment in patients with HIV/AIDS in Western Iran. Material and methods: This study was performed among all patients diagnosed with HIV/AIDS in Kermanshah Province for 25 years, from 1995 till 2019. Adherence to treatment in these patients was divided into three categories according to the World Health Organization definition, i.e., non-adherence, cessation, and adherence to treatment. Using single-variable and multi-variable logistic regression, the effect of important variables in four models was modified, and the effect of each of behavioral risk factors was analyzed in patients with non-adherence or experienced cessation compared to those who adhered to ARV. Results: Of the 2,867 patients with HIV/AIDS, 2,449 (85.42%) were males. The mean age of HIV infection was 33.36 ± 11.8 years. In 1995, less than 10 percent of people received treatment, and in 2019, it was more than 67 percent. All behavioral risk factors increased non-adherence to medication and cessation of ARV. In general, after controlling confounding variables, except for needle sharing, all behavioral variables affected ARV treatment. The greatest impact on non-adherence to medication was history of drug abuse, history of imprisonment, history of injection drug use, and sex with non-spouse, with a chance of 10.87 (range, 7.21-16.39), 3.94 (range, 2.84-5.46), 3.86 (range, 2.47-6.03), and 3.38 (range, 2.19-5.23) times more than patients without these risk factors, respectively. Conclusions: Although the process of receiving treatment has been increasing since 2005, the nonadherence to medication is still high in high-risk groups; therefore it is important to focus more on reducing non-adherence and eventual cessation of treatment. In particular, more attention is necessary for health education and raising the level of awareness of these groups. [ABSTRACT FROM AUTHOR]

HIV pre-exposure prophylaxis (HIV-PrEP) is effective in reducing the likelihood of HIV acquisition in HIV-negative people at high risk of exposure. Guidelines recommend testing for sexually transmitted infections (STIs) before starting, and periodically on PrEP, including bacterial infections, HIV, hepatitis C virus, and, for those who are non-immune, hepatitis B virus. Diagnosed infections can be promptly treated to reduce onward transmission. HTLV-1 is not mentioned; however, it is predominantly sexually transmitted, causes adult T-cell leukaemia/lymphoma (ATL) or myelopathy in 10% of those infected, and is associated with an increased risk of death in those without any classically HTLV-associated condition. The 2021 WHO Technical Report on HTLV-1 called for the strengthening of global public health measures against its spread. In this scoping review, we, therefore, (1) discuss the epidemiological context of HIV-PrEP and HTLV-1 transmission; (2) present current knowledge of antiretrovirals in relation to HTLV-1 transmission prevention, including nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs); and (3) identify knowledge gaps where data are urgently required to inform global public health measures to protect HIV-PrEP users from HTLV-1 acquisition. We suggest that systematic seroprevalence studies among PrEP-using groups, including men who have sex with men (MSM), people who inject drugs (PWIDs), and female sex workers (FSWs), are needed. Further data are required to evaluate antiretroviral efficacy in preventing HTLV-1 transmission from in vitro studies, animal models, and clinical cohorts. PrEP delivery programmes should consider prioritizing the long-acting injectable INSTI, cabotegravir, in HTLV-1 endemic settings.

Background: Recent reports have indicated the use of antiretroviral (ARV) drugs to boost animal production in neighboring Uganda, with further reports of use in several African countries., Methods: This cross-sectional study was conducted in nine districts in Tanzania, and involved screening for the presence of three first-line ARVs (lamivudine, nevirapine, and efavirenz) residues in the muscle and blood of domestic pigs and broiler chickens, and in sampled animal feed and water. Residues were determined using liquid chromatography and mass spectrometry (LC-MS/MS). The method involved calibration of the lower limit of quantitation (LLOQ) and limit of detection (LOD). ARVs were detected and quantified using the Multiple Reaction Monitoring (MRM) system., Results: 131 (66.8%) of the 196 samples of muscle, blood, and animal feed were found to contain lamivudine residues, with the highest concentration detected in domestic pig blood and muscle (7.58mg/kg) and the lowest concentration (0.01 mg/kg) in broiler chicken feed. There was a significant relationship between the presence of lamivudine by sample type and sample origin (p=0.000). Nevirapine and efavirenz drugs were not detected in any of the collected samples. No ARV residues were detected in water samples (n=37)., Conclusion: This study confirms the use of ARVs in animal production in Tanzania as evidenced by the presence of residues in animal feeds. We found lamivudine residues in domestic pigs and broiler chickens at concentrations higher than those recently reported in other East African studies. Farmers living with HIV may be using ARVs from their prescribed medications, which may lead to poor adherence and the emergence of drug resistance. Besides direct human and animal health issues, these residues in animal feeds and animal excreta can lead to environmental contamination leading to several negative impacts. We recommend a total ban on human-designated ARVs in animal production and advocate for comprehensive studies and monitoring systems across African countries to reveal potential societal and other reasons for their use and provide comprehensive solutions using One Health approaches., Competing Interests: Additional Declarations: The authors declare no competing interests. Competing interests The authors declare that they have no competing interests.

HIV treatment adherence in Indonesia is a major challenge. Although previous studies have demonstrated several barriers and facilitators to adherence, studies providing a comprehensive analysis from both PLHIV and HIV service providers’ perspectives are limited, especially in Indonesia. In this qualitative study with 30 people living with HIV on treatment (PLHIV-OT) and 20 HIV service providers (HSPs), we explored, via online interviews, the barriers and facilitators to antiretroviral therapy (ART) adherence using a socioecological approach. Both PLHIV-OT and HSPs reported stigma as a major barrier at each socioecological level, including public stigma at the societal level, stigma in healthcare settings, and self-stigma at the intrapersonal level. Stigma reduction must therefore be prioritized. PLHIV-OT and HSPs also reported support from significant others and HSPs as the foremost facilitators to ART adherence. The enablement of support networks is thus an important key to improved ART adherence. Overall, the societal level and health system barriers to ART adherence should be addressed in order to remove barriers and enhance the facilitators at the subordinate socioecological levels.

The increasing of HIV/AIDS every year become a health problem in Indonesia. Patients of HIV/AIDS should use longterm Antiretroviral (ARV) therapy of antiretroviral therapy to support the success of antiretroviral therapy. The objective of this study was to know and compare the effectivity of four ARV combination. The four ARV combination are combination A (AZT+3TC+NVP), combination B (AZT+3TC+EFV), combination C (TNF+3TC+NVP), combination D (TNF+3TC+EFV) base on increasing CD4. This study cohort-longitudinal design. Samples for this study were taken by total sampling using all data of HIV/AIDS outpatients at RS Fartmawati on 2016. The inclusion criteria were patients of (≥17 years old), received treatment of either one of the four ARV combination, and had data of CD4 from laboratory result before and 6-12 months after the treatment. Data were taken from patients medical record and analyzed with non-parametric Kruskal Wallis-test. The study results showed of 124 patients had increased the CD4 mean >100 sel/mm3 one year after the treatment. The average rate of increment of each combination of antiretroviral therapy on a median CD4 cell count of 1 year was a combination of A (73.93), combination B (70.87), combination C (48.73), combination D (55.57) and there was a significant difference in CD4 cell gain in patients taking combination A-C (p value = 0.047), combination A-D (p value = 0.041), and combination B-D (p value = 0.045) at the evaluation on 1 year. Conclusion, combination A is more effective than combination B, D and C.

BackgroundIn the “treat all” era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men.MethodsFrom 2009–2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men via periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4+ T cell counts < 350/µL within 3–24 months post-infection. Kaplan−Meier and Cox-regression analyses were conducted to identify predictors of rapid progression.ResultsAmong 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection (adjusted hazard ratio [aHR] 1.7, 95% confidence interval [CI] 1.2–2.3], depression (aHR 1.9, 95% CI 1.5–2.6), baseline CD4+ T cell count < 500/μL (aHR 3.5, 95% CI 2.4–5.1), higher baseline HIV viral load (aHR 1.6, 95% CI 1.2–2.3), acute symptoms lasting ≥ 2 weeks (aHR 1.6, 95% CI 1.1–2.2), higher body mass index (aHR 0.9, 95% CI 0.9–1.0), higher HIV viral load (aHR 1.7, 95% CI 1.4–2.1), set point viral load at 3 months (aHR 2.0, 95% CI 1.6–2.5), each 100-cell/μL decrease in CD4+ T cell count at 3 months (aHR 2.2, 95% CI 1.9–2.5), and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 (all p < 0.05).ConclusionAlmost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4+ T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified via simple indicators such as body mass index and routine blood test parameters in low and middle-income countries.

Background: In the "treat all" era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men. Methods: From 2009–2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men via periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4+ T cell counts < 350/µL within 3–24 months post-infection. Kaplan−Meier and Cox-regression analyses were conducted to identify predictors of rapid progression. Results: Among 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection (adjusted hazard ratio [aHR] 1.7, 95% confidence interval [CI] 1.2–2.3], depression (aHR 1.9, 95% CI 1.5–2.6), baseline CD4+ T cell count < 500/μL (aHR 3.5, 95% CI 2.4–5.1), higher baseline HIV viral load (aHR 1.6, 95% CI 1.2–2.3), acute symptoms lasting ≥ 2 weeks (aHR 1.6, 95% CI 1.1–2.2), higher body mass index (aHR 0.9, 95% CI 0.9–1.0), higher HIV viral load (aHR 1.7, 95% CI 1.4–2.1), set point viral load at 3 months (aHR 2.0, 95% CI 1.6–2.5), each 100-cell/μL decrease in CD4+ T cell count at 3 months (aHR 2.2, 95% CI 1.9–2.5), and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 (all p < 0.05). Conclusion: Almost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4+ T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified via simple indicators such as body mass index and routine blood test parameters in low and middle-income countries. [ABSTRACT FROM AUTHOR]

The human cell cycle is a tightly regulated process with checkpoints in place to ensure genomic integrity. Cyclin/cyclin dependent kinases (CDKs) complexes drive the progression of the cell cycle while CDK-inhibitors (CDKIs) halt the cell cycle. Deregulation of the cell cycle is a hallmark of lung cancer. TP53 and FOXO transcription factors share similar mechanisms in the regulation of the cell cycle. Lung carcinogenesis in the antiretroviral (ARV) era remains to be understood. This study aimed at mapping the biological pathways related to the human cell cycle that are influenced by the ARVs (Efavirenz-EFV and Lopinavir/ritonavir-LPV/r) treatment in A549 and MRC-5 lung cells. For this purpose, Reactome database was used to map these pathways. In addition, the Database for Annotation, Visualisation and Integrated Discovery (DAVID) was used for functional enrichment analysis in a set of genes and to visualise differentially expressed genes within a particular KEGG pathway, and also to perform Gene Ontology. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to determine the protein-protein interaction of the differentially expressed gene (DEG) targets. Reactome analysis revealed a decrease in DNA replication and an increase in response to external stimuli and DNA repair genes in both normal and adenocarcinoma lung cancer models. A further increase in apoptotic genes is observed in the cancer cells in response to ARV treatment. Interestingly, the FOXO pathway was also shown to be upregulated in the test (ARV) groups. KEGG pathway shows a reduction in cyclin/CDK activity in ARV treated models. STRING analysis illustrates a direct and strong interaction between DNA damage and response (DDR) genes upregulated by ARV exposure. Analysis from all three databases suggests the cytotoxic and anti-proliferative effects of EFV and LPV/r on lung cancer.

Peningkatan kasus HIV/AIDS yang terjadi setiap tahun menjadi masalah kesehatan di Indonesia. Pasien HIV/AIDS harus menggunakan terapi antiretroviral (ARV) seumur hidup untuk menekan replikasi HIV, sehingga diperlukan pemantauan untuk mendukung keberhasilan terapi ARV. Penelitian ini bertujuan untuk membandingkan efektivitas empat kombinasi ARV yang terdiri dari kombinasi A (AZT+3TC+NVP), kombinasi B (AZT+3TC+EFV), kombinasi C (TNF+3TC+NVP), kombinasi D (TNF+3TC+EFV) dengan menilai kenaikan CD4. Desain studi penelitian adalah cohort longitudinal. Sampel penelitian yang digunakan yaitu seluruh pasien HIV/AIDS rawat jalan di RS Fatmawati Tahun 2016 yang memenuhi kriteria inklusi: pasien dewasa (≥17 tahun) yang mendapatkan terapi salah satu kombinasi ARV, dan memiliki data pemeriksaan CD4 awal, 6-12 bulan setelah terapi. Data diambil dari rekam medis pasien dan dianalisis dengan non-parametrik Kruskal wallis. Hasil penelitian pada 124 pasien menunjukkan semua kombinasi ARV efektif meningkatkan nilai CD4>100 sel/mm3 setahun. Rata-rata kenaikan CD4 masing-masing kombinasi ARV pada pemeriksaan 1 tahun adalah kombinasi A (73.93), kombinasi B (70.87), kombinasi C (48.73), kombinasi D (55.57). dan terdapat perbedaan kenaikan nilai CD4 yang bermakna pada pasien yang menggunakan ARV kombinasi A-C (p value=0,047), kombinasi A-D (p value=0,041), dan ARV kombinasi B-D (p value=0,045) pada saat evaluasi penggunaan rata-rata 1 tahun. Kesimpulan, kombinasi A lebih efektif daripada kombinasi B, D dan C.

There is a need to establish consensus for harmonization in antiretroviral (ARV) therapy (ART) switch treatment strategy and address the dilemma that exists in terms of subpar immune response to therapy or an immunologic deterioration while on therapy. The purpose of this review is to identify the factors that contribute to ARV treatment failure, such as insufficient dosage, drug interactions, poor adherence, drug resistance, and poor medication absorption. It is crucial to adopt a more efficient strategy to address this challenging dilemma. After ARV treatment failure, the aim of therapy is virologic suppression, which targets plasma viral load below the limits of detection as assessed by very sensitive tests with lower limits of quantification of 20 to 75 RNA copies/ml. The therapeutic objectives when complete virologic suppression is not possible, should be to maintain or restore immunologic function, stop the progression of the clinical illness, and minimize the emergence of new drug resistance that could further restrict the options for ARV drugs. Treatment history and drug-resistance testing, including the findings of previous and ongoing resistance tests, should be considered while selecting ARV regimens. Hence, the treatment approach post-ARV failure can be personalized based on clinical, immunologic, virologic, or as a mix of the three domains on a case-to-case basis. The evaluation of projected ARV activity should be based on treatment history and previous resistance test findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sharma et al.)

Background In 2018, the World Health Organisation (WHO) released interim guidelines, advising a change of regimens to dolutegravir-based first- and second-line antiretroviral therapy (ART), based on which, in 2021, the National Aids Control Organisation (NACO) updated its guidelines to include the tenofovir + lamivudine + dolutegravir (TLD) regimen as a first line of therapy for all people living with HIV (PLHIV) and second- and third-line regimens to dolutegravir-based regimens. Considering this change of regimen, the adverse drug reaction (ADR) profiling and longitudinal prescription pattern of antiretroviral and concomitant medications in adult patients at the ART centre of a tertiary care hospital were assessed in this study. Methods Ninety-seven PLHIV out of all the patients who attended the ART centre from September 2021 to July 2022 were enrolled and followed up for six months. The ADRs that occurred during this period were collected along with details of prescription patterns and analyzed by descriptive statistics. Causality assessment for ADR was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Results Seventy-eight percent (n=76 out of 97) of patients experienced at least one ADR, and 128 ADRs were seen in 97 patients. The most common ADRs were increased alkaline phosphatase (39.0%, n=128), dyslipidaemia (12.5%, n=128), and nephrotoxicity (10.1%, n=128). The drug most suspected of causing ADRs was dolutegravir (27.5%, n=342). The most common therapeutic regimen was TLD (71.2%, n=97). The most prescribed drug was lamivudine (30.6%, n=1183). The most prescribed concomitant medication was cotrimoxazole (15%, n=312). Conclusions Dolutegravir-based regimens have been implemented for PLHIV in a phased-out manner from previous non-dolutegravir-based ART regimens, which is in line with the recent NACO guidelines. However, it has also led to an increase in dolutegravir-associated ADRs like increased alkaline phosphatase, dyslipidaemia, and nephrotoxicity. Continuous monitoring of prescriptions and ADRs can add to our knowledge regarding their use and ADRs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sekar et al.)

Sexually transmitted infections affect hundreds of millions of people worldwide. Both human immunodeficiency virus (HIV-1 and −2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir disoproxil fumarate (TDF), exhibited sustained-release for up to 4 weeks, and provided complete in vitro protection against HSV-2 and HIV-1 for 24 h and 1 wk, respectively, based on the doses tested. In vitro cell culture and EpiVaginal tissue tests confirmed the safety of fibers in vaginal and cervical cells, highlighting the potential of PLGA and PLCL EFs as multipurpose next-generation drug delivery vehicles. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. Design: 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. Results: The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm3. Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. Conclusion: In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use. [Copyright &y& Elsevier]

Abstract: HIV-exposed seronegative individuals (HESNs) are persons who remain seronegative despite repeated exposure to HIV, suggesting an in vivo resistance mechanism to HIV. Elucidation of endogenous factors responsible for this phenomenon may aid in the development of new classes of microbicides and therapeutics. We compared cervicovaginal protein abundance profiles between high-risk HESN and two control groups: low-risk HESN and HIV-positives. Four iTRAQ-based quantitative experiments were performed using samples classified based on presence/absence of particular gynaecological conditions. After statistical analysis, two proteins were shown to be differentially abundant between high-risk HESNs and control groups. Serpin A5, a serine proteinase inhibitor and Myeloblastin, a serine protease, were up- and downregulated, respectively. Commercially available ELISA assays were used to confirm differential Serpin A5 levels. These results suggest that HIV resistance in CVF of HESNs is the result of a delicate balance between two complementary mechanisms: downregulation of serine proteinases and upregulation of their inhibitors. [Copyright &y& Elsevier]

Abstract: Background: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. Objectives: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. Study design: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n =467) and HIV-negative (n =2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. Results: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200cells/μl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07–1.59), multiple HPV types (PRa 1.52; 95% CI 1.14–2.01), and HPV-16 (PRa 9.00; 95% CI 1.66–48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45–3.24) compared to those with CD4 counts 500cells/μl or above. Conclusion: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations. [Copyright &y& Elsevier]

Concern has been raised about the ART patients relinquishing the principles of the ABC (abstain, be faithful and condomise) approach to the prevention of HIV infection once the positive effects of ART are experienced. Ten years after the launch of the national ART programme in Swaziland, it remained unknown to what extent this concern applied to ART patients attending one ART clinic in Swaziland. This study sampled 340 ART patients from one ART clinic in Swaziland. A purposely designed questionnaire covering four indicators of sexual practice namely: number of children hoped for, type of sexual relationship, number of sexual partners and condom use were administered to respondents by four field workers. The main statistically significant findings of this study included: * Females were more likely to disclose their HIV status than males * Males were more likely to use condoms than females * There was an association between religion and disclosure, but clergy were the least "trusted" persons to whom the respondents would disclose * The notion of increased promiscuity accompanied with prolonged ART, was contradicted These finding must be interpreted within the context of the target population -- ART patients attending one ART clinic in Swazialnd. [ABSTRACT FROM AUTHOR]

Introduction: Nutrition and HIV are closely related. Any immune impairment as a result of HIV leads to malnutrition, which in turn, can also lead to reduced immunity, thus contributing to a more rapid progression to AIDS. Methods: This cross-sectional study determined the nutritional status of children living with HIV and are receiving antiretroviral medication in the Klang Valley. A total of 95 children aged one to eighteen years old were recruited between September 2008 and February 2009. Data collected included socio-economic status, anthropometric measurements, dietary intake, medical history and serum levels of selected micronutrients specific for immunity. Results: The mean age of the children was 8.4±3.9 years and the mean duration on antiretroviral medications was 68.3±38.3 months. Anthropometric assessment found that 9.5% of the children were underweight and 31.6% were overweight. In contrast, 20.8% were stunted and 14.6% severely stunted. Biochemical indicators showed that 10.4% had deficiency in vitamin A while 12.5% had deficiency in selenium. Total cholesterol and HDL-C levels were found to be low in 30.5% and 10.5% of the children respectively. Conclusion: Dietary assessment showed almost all the children did not achieve the recommended energy intake for their age groups and almost half of the children did not achieve the RNI for selenium and vitamin A. This study provides an insight on the nutritional status of children living with HIV. [ABSTRACT FROM AUTHOR]

Objective: To compare growth and body composition of uninfected children exposed to HIV with a contemporary HIV-unexposed group and to US references. Study design: Uninfected children exposed to HIV under 2 years were enrolled into a longitudinal observational study and unexposed children under 2 years of age in a cross-sectional evaluation. Weights, lengths, head circumferences, skinfold thicknesses, and arm and thigh circumferences were measured and adjusted for age using Centers for Disease Control and National Health and Nutrition Examination Survey standards. Uninfected children exposed to HIV were compared with an unexposed nearest-neighbor matched comparison group. Uninfected children exposed to HIV were compared by age to Centers for Disease Control standards for growth measures and National Health and Nutrition Examination Survey standards for body composition. Results: One hundred eleven uninfected children exposed to HIV and 82 children not exposed to HIV were evaluated. For the matched comparison for both groups, the mean age was 10 months, 59% were male, and 73% were African American. No statistical differences were found in anthropometric measurements between uninfected children who were or were not exposed to HIV. Uninfected children exposed to HIV were smaller than US standards at birth with mean (SD) weight-for-age and weight-for-length z-scores of −0.39 (1.06); P = .002 and −0.35 (1.04); P = .005, respectively. Over the first 2 years of life, there was a trend toward increasing weight-for-age z-score, length-for-age z-score, and weight-for-length z-score in uninfected children exposed to HIV. Subscapular and triceps skinfolds among uninfected children exposed to HIV were lower than national standards and there was a trend that mid-upper arm circumference decreased over time. Conclusions: Growth and body composition of uninfected children who were or were not exposed to HIV were similar. Uninfected children exposed to HIV weigh less at birth and show a pattern of slightly accelerated growth in the first 2 years of life. Uninfected children exposed to HIV had less subcutaneous fat and decreasing mid-upper arm circumference over time when compared with US standards. [Copyright &y& Elsevier]

Background: Patients with HIV often have multiple medications besides antiretrovirals (ARV). Medication regimen complexity-formulations, dosing frequencies, and additional directions-expands pill burden by considering self-care demands. Studies show an inverse association between ARV adherence and medication complexity for ARVs only. Patient-level medication regimen complexity beyond ARV complexity is unknown., Objective: To measure and characterize Patient-level Medication Regimen Complexity Index (pMRCI) and Antiretroviral Medication Regimen Complexity Index (ARCI) for patients in 2 HIV clinics. We hypothesized that an all-medication complexity metric will exceed disease-state-defined complexity metrics; for ARVs only, the pMRCI score will be smaller than the ARCI score by capturing fewer features of regimens. Associations between complexity and adherence were not assessed., Method: Electronic records supplied a retrospective, random sample of adult patients with HIV; medication lists were used to code the pMRCI (n=200). A random subsample (n=66) was coded using ARCI for ARV regimens only., Result: Medication counts ranged from 1 to 27; pMRCI scores ranged from 2 to 67.5. ARVs contributed roughly 25% to the pMRCI; other prescriptions contributed about 66%. Dosing frequency made the largest contribution of all components (62%) to the pMRCI. For ARVs, pMRCI and ARCI scores did not differ statistically., Conclusion: Unique dosing frequencies raised complexity and may provide opportunities for intervention. Other prescriptions drove pMRCI scores, suggesting that HIV management programs should review all medications. A patient-level approach added value to understanding the role of medications in patient complexity; future work can assess association of pMRCI with adherence and patient outcomes., (© The Author(s) 2014.)