Revolutionizing HIV-1 Viral Load Monitoring in India: The Potential of Dried Blood Spot Analysis for Expanding Access and Improving Care.

India continues to grapple with a significant burden of HIV infections. Despite notable progress in prevention and treatment efforts, multiple challenges, such as high-risk populations, inadequate testing facilities, and limited access to healthcare in remote areas, persist. Though the Government of India offers HIV-1 plasma viral load testing at various medical centers, aiding treatment decisions and monitoring antiretroviral therapy effectiveness, enhancing care for individuals living with HIV under the National AIDS Control Program (NACP), the nation's large population and diverse demographics further complicate its outreach and response. Hence, strategic interventions and alternative methods of testing remain crucial to curbing HIV transmission and improving the quality of life for those affected. Dried blood spot (DBS) sampling has emerged as a convenient and cost-effective alternative for HIV-1 viral load testing, revolutionizing the landscape of diagnostic and monitoring strategies for HIV infection. Though the plasma-based viral load remains the gold standard for monitoring HIV-1, DBS-based HIV-1 viral load testing holds immense promise for improving access to care, particularly in resource-limited settings where traditional plasma-based methods may be logistically challenging. DBS entails the collection of a small volume of blood onto filter paper, followed by drying and storage. This approach offers numerous advantages, including simplified sample collection, transportation, and storage, reducing the need for cold-chain logistics. Recent studies have demonstrated the feasibility and accuracy of DBS-based HIV-1 viral load testing, revealing a strong correlation between DBS and plasma measurements. Its implementation can enhance the early detection of treatment failure, guide therapeutic decisions, and ultimately contribute to better clinical outcomes for HIV-infected individuals. Hence, this review explores the principles, advancements, feasibility, and implications of DBS-based HIV-1 viral load testing.

Optimizing rosemary oil nanoemulsion loaded with nelfinavir and epigallocatechin gallate: A Design Expert® endorsed approach for enhanced neuroAIDS management.

This study focuses on optimizing the delivery of Nelfinavir (NFV), a vital protease inhibitor in antiretroviral therapy, and Epigallocatechin gallate (EGCG), a potent adjunctive anti- human immunodeficiency virus (anti-HIV) agent found in green tea. The challenge lies in NFV's low intrinsic dissolution rate, significant p-gp efflux, and high hepatic metabolism, necessitating frequent and high-dose administration. Our objective was to develop a nanoemulsion loaded with NFV and EGCG to enhance oral delivery, expediting antiretroviral effects for NeuroAIDS treatment. After meticulous excipient screening, we selected Tween 40 as the surfactant and polyethylene glycol 400 (PEG 400) as the co-surfactant. Employing a Quality by Design (QbD) approach with statistical multivariate methods, we optimized the nanoemulsion that exhibited a droplet size of 83.21 nm, polydispersity index (PDI) of 2.289, transmittance of 95.20 %, zeta potential of 1.495 mV, pH of 6.95, refractive index of 1.40, viscosity of 24.00 ± 0.42 mPas, and conductivity of 0.162 µS/cm. Pharmacokinetic studies demonstrated superior in vivo absorption of the optimized nanoemulsion compared to NFV and EGCG suspension. The optimized nanoemulsion showcased higher Cmax of NFV (9.75 ± 1.23 µg/mL) and EGCG (27.7 ± 1.22 µg/mL) in the brain, along with NFV (26.44 ± 1.44 µg/mL) and EGCG (313.20 ± 5.53 µg/mL) in the plasma. This study advocates for the potential of NFV and EGCG-loaded nanoemulsion in combination antiretroviral therapy (cART) for effective NeuroAIDS management.

A nanoemulsified formulation of dolutegravir and epigallocatechin gallate inhibits HIV-1 replication in cellular models.

Nanotechnology offers promising avenues for enhancing drug delivery systems, particularly in HIV-1 treatment. This study investigates a nanoemulsified formulation combining epigallocatechin gallate (EGCG) with dolutegravir (DTG) for managing HIV-1 infection. The combinatorial interaction between EGCG and DTG was explored through cellular, enzymatic, and molecular studies. In vitro assays demonstrated the potential of a dual drug-loaded nanoemulsion, NE-DTG-EGCG, in inhibiting HIV-1 replication, with EGCG serving as a supplementary treatment containing DTG. In silico molecular interaction studies highlighted EGCG's multifaceted inhibitory potential against HIV-1 integrase and reverse transcriptase enzymes. Further investigations are needed to validate the formulation's efficacy across diverse contexts. Overall, by integrating nanotechnology into drug delivery systems, this study represents a significant advancement in managing HIV-1 infection.

A protocol for feasibility of plasma based GeneXpert platform and Dried Blood Spot (DBS) based Abbott platform for HIV-1 viral load testing among the people living with HIV attending ART centers in India.

BACKGROUND: HIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type. METHODS: This ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation. RESULTS: The proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools. CONCLUSION: If found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.

The involvement of microRNAs in HCV and HIV infection.

Approximately 2.3 million people are suffering from human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection worldwide. Faster disease progression and increased mortality rates during the HIV/HCV co-infection have become global health concerns. Effective therapeutics against co-infection and complete infection eradication has become a mandatory requirement. The study of small non-coding RNAs in cellular processes and viral infection has so far been beneficial in various terms. Currently, microRNAs are an influential candidate for disease diagnosis and treatment. Dysregulation in miRNA expression can lead to unfavorable outcomes; hence, this exact inevitable nature has made various studies a focal point. A considerable improvement in comprehending HIV and HCV mono-infection pathogenesis is seen using miRNAs. The prominent reason behind HIV/HCV co-infection is seen to be their standard route of transmission, while some pieces of evidence also suspect viral interplay between having a role in increased viral infection. This review highlights the involvement of microRNAs in HIV/HCV co-infection, along with their contribution in HIV mono- and HCV mono-infection. We also discuss miRNAs that carry the potentiality of becoming a biomarker for viral infection and early disease progression.