Emerging Trends in the Long-acting Antiretroviral Therapy: Current Status and Therapeutic Challenges

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajpushpa Labh ◽  
Rachna Gupta
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Drug Distribution ◽  
Antiretroviral Drugs ◽  
Current Status ◽  
People Living With Hiv ◽  
Viral Reservoirs ◽  
Emerging Trends ◽  
Gradual Development ◽  
Long Acting

: Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of People Living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in fight against HIV. Few long acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, longacting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. LongActing Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.

Neuro-AIDS: Current status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment.

2020 ◽  
Vol 15 ◽  
Author(s):  
Smita P. Kakad ◽  
Sanjay J. Kshirsagar
Keyword(s):  
Nervous System ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Sensory Neuropathy ◽  
Current Status ◽  
Viral Reservoir ◽  
Viral Reservoirs ◽  
Highly Active ◽  
Aids Therapy ◽  
The Brain

Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as NeuroAIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions. Materials/Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which acts as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination antiretroviral therapy. Results/Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful to treat neuro-AIDS and related disorders effectively.

scholarly journals Antiretroviral Drugs Impact Autophagy with Toxic Outcomes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman
Keyword(s):  
Quality Control ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Viral Suppression ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Foreign Material ◽  
Complete Understanding ◽  
Living With Hiv ◽  
Target Effects

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.

Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9–15 Months in 14 Triangular Clinics in Iran, 2015–2016

Intervirology ◽  
2018 ◽  
Vol 61 (6) ◽  
pp. 292-300 ◽  
Author(s):  
Minoo Mohraz ◽  
Katayoun Tayeri ◽  
Hengameh Namdari Tabar ◽  
Zahra Bayat Jozani ◽  
Leila Sadeghi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
People Living With Hiv ◽  
Hiv Drug Resistance ◽  
Living With Hiv

scholarly journals Reasons People Living with HIV Might Prefer Oral Daily Antiretroviral Therapy, Long-Acting Formulations, or Future HIV Remission Options

2020 ◽  
Vol 36 (12) ◽  
pp. 1054-1058
Author(s):  
Karine Dubé ◽  
Danielle M. Campbell ◽  
Kelly E. Perry ◽  
John T. Kanazawa ◽  
Parya Saberi ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
People Living With Hiv ◽  
Long Acting ◽  
Living With Hiv

Optimal antiretroviral therapy for aging

Sexual Health ◽  
2011 ◽  
Vol 8 (4) ◽  
pp. 534 ◽  
Author(s):  
Damien V. Cordery ◽  
David A. Cooper
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Treatment Guidelines ◽  
Age Groups ◽  
Developed Countries ◽  
Neurological Complications ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Metabolic Complications ◽  
Long Term Treatment

The introduction of highly active antiretroviral therapy (HAART) has irrevocably changed the nature of the HIV epidemic in developed countries. Although the use of HAART does not completely restore health in HIV-infected individuals, it has dramatically reduced morbidity and mortality. Increases in life expectancy resulting from effective long-term treatment mean that the proportion of older people living with HIV has increased substantially in the past 15 years. Increasing age is associated with many complications including cardiovascular disease, neurological complications, kidney and liver dysfunction, and metabolic complications such as dyslipidaemia and diabetes. HIV infection and antiretroviral drugs have also been associated with similar complications to those seen with increasing age. The increase in HIV prevalence in older age groups has not been accompanied by the development of treatment guidelines or recommendations for appropriate antiretroviral therapy or clinical management in these patients.

scholarly journals Transmitted Drug Resistance in Antiretroviral Therapy-Naive Persons With Acute/Early/Primary HIV Infection: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxiang Guo ◽  
Yaxin Wu ◽  
Yang Zhang ◽  
Xinchao Liu ◽  
Aixin Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Meta Analysis ◽  
Antiretroviral Drugs ◽  
Cochrane Library ◽  
Transmitted Drug Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Primary Hiv Infection

Background: The widespread use of antiretroviral therapy (ART) has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with primary HIV infection (PHI)/AHI/early HIV infection (EHI) and to describe the critical drug-resistant mutations.Methods: We systematically searched the literature between January 1, 2008, and April 30, 2021, in PubMed, Web of Science, Embase, and the Cochrane Library. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE.Results: The data of this meta-analysis come from 12 observational studies, covering 3,558 ART-naive individuals with PHI, AHI, or EHI. The overall prevalence of HIV-TDR is 9.3% (95% CI: 6.8%–11.8%, I2 = 81.1%, in 11 studies). The prevalence of resistance by drug class is the highest for the nonnucleoside reverse transcriptase inhibitors (NNRTIs) at 5.7% (95% CI: 2.9%–8.5%, I2 = 96.6%, in 11 studies), followed by nucleoside reverse transcriptase inhibitors (NRTIs) at 3.4% (95% CI: 1.8%–5.0%, I2 = 86.3%, in 10 studies) and protease inhibitors (PIs) at 3.3% (95% CI: 2.7%–3.9%, I2 = 15.6%, in 10 studies). The prevalence of TDR to integrase inhibitors (INIs) is 0.3% (95% CI: 0.1%–0.7%, I2 = 95.9%, in three studies), which is the lowest among all antiretroviral drugs.Conclusion: The overall prevalence of TDR is at a moderate level among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.

scholarly journals EVALUATION ON THE NUMBER OF CD4 T CELLS AND ANTIRETROVIRAL SIDE EFFECTS IN PATIENTS WITH AIDS

2016 ◽  
Vol 3 (2) ◽  
pp. 96
Author(s):  
Siti Qamariyah Khairunisa ◽  
Irine Normalina ◽  
Nasronudin Nasronudin
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Cd4 T Cells ◽  
Secondary Data ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Before And After ◽  
Record Card ◽  
Living With Hiv

Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occur within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy and side effects arising during the taking of ARVs. Samples were collected from 10 patients infected by HIV/AIDS in a clinic in Surabaya. This study is an analytical survey. Data collection was conducted using secondary data obtained from the medical record card status on HIV paients in a clinic in Surabaya. Data results showed that the side effects that often occur in people with AIDS are appetite loss (90%), headache (80%), insomnia (80%) and nausea (70%). While many combinations of antiretroviral drugs have side effects such as a combination of AZT +3 TC + EFV, d4T +3 TC + followed by EFV and AZT +3 TC + NVP. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cellsin patients living with HIV, as shown by the tendency of an increase in the number of CD4 T-cells in 8 out of 10 AIDS patients who received a antiretroviral therapy.

scholarly journals Prevalence of Nonsuppressed Viral Load and Associated Factors Among Adults Receiving Antiretroviral Therapy in Eswatini, Lesotho, Malawi, Zambia, and Zimbabwe (2015-2017): Results from Population-Based Nationally-Representative Surveys

2020 ◽  
Author(s):  
Andreas D Haas ◽  
Elizabeth Radin ◽  
Avi J Hakim ◽  
Andreas Jahn ◽  
Neena Philip ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Virologic Failure ◽  
Scale Up ◽  
Female Gender ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Second Line ◽  
Viral Load Suppression ◽  
Factors Associated

Introduction: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a target of ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) to have viral load suppression (VLS). We examined factors associated with nonsuppressed viral Load (NVL). Methods: We included PLHIV receiving ART aged 15-59 years from Eswatini, Lesotho, Malawi, Zambia, and Zimbabwe. Blood samples from PLHIV were analyzed for HIV RNA and recent exposure to antiretroviral drugs (ARVs). Outcomes were NVL (viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL), and receiving second-line ART. We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. Results: The prevalence of NVL was 11.2%: 8.2% experienced VF, and 3.0% interrupted ART. Younger age, male gender, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married, and residing in Zimbabwe, Lesotho, or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female gender, shorter ART duration, higher CD4 count, and alcohol use were associated with higher odds for interrupted ART and lower odds for VF. Many people with VF (44.8%) had CD4 counts <200 cells/μL, but few (0.31% per year) switched to second-line ART. Conclusions: Countries are approaching UNAIDS VLS targets for adults. Treatment support for people initiating ART with asymptomatic HIV infection, scale-up of viral load monitoring, and optimized ART regimens may further reduce NVL prevalence.

scholarly journals EVALUATION ON THE EFFECT OF ANTIRETROVIRAL DRUGS ON CD4 T-CELL AND THE INCREMENT OF BODY WEIGHT AMONG HIV-AIDS PATIENTS IN SURABAYA

2016 ◽  
Vol 3 (2) ◽  
pp. 92
Author(s):  
Edith Frederika ◽  
Irine Normalina ◽  
Nasronudin Nasronudin ◽  
Rury Mega
Keyword(s):  
T Cells ◽  
Body Weight ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Cd4 T Cells ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Antiretroviral Drug ◽  
Before And After ◽  
Living With Hiv

Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occurr within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy, the side effects arising during the taking of ARVs are related to the increment of body weight among the HIVAIDS patients. Subjects were then narrowed down from 25 to 12 due to the incomplete data. The results showed that the top three most side effects which often occur in people with AIDS are appetite loss (20.0%), nausea (17.8%), and diarrhoea (15.6%). Meanwhile, about 58% of the subjects experienced increment of their body weight, and 42% were losing weight due to the side effects of the ARV therapy. Among those who lost their body weight, 50% were in the productive ages between 21–30 years old. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cells in patients living with HIV, as shown by the tendency of an increment in the number of CD4 T-cells in patients who received antiretroviral therapy. However, around 42% of those patients were losing weight because of the side effects of the therapy. Therefore, the importance of giving specific nutrient to overcome with the weight loss is needed to be given to the patients HIV instead of only giving the ARV treatment.

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