An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

2020 ◽  
Vol 27 (5) ◽  
pp. 760-794 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
António J. Preto ◽  
Beatriz Bueschbell ◽  
Pedro Matos-Filipe ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Targeted Delivery ◽  
Highly Active Antiretroviral Therapy ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Reverse Transcriptase Inhibitors ◽  
Replication Process ◽  
Antiretroviral Agents ◽  
Multiple Drugs

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

scholarly journals HIV-1 CRF63_02A6 models as a tool for evaluating efficacy of developing antiretroviral drugs

2020 ◽  
Vol 10 (4) ◽  
pp. 769-774
Author(s):  
D. P. Zyryanova ◽  
N. V. Bogacheva ◽  
A. V. Totmenin ◽  
N. M. Gashnikova
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Federal District ◽  
Antiretroviral Drugs ◽  
Infection Process ◽  
Reverse Transcriptase Inhibitors ◽  
Infectious Molecular Clones ◽  
Hiv 1

Highly active antiretroviral therapy (HAART) allows not only to control the infection process in certain patient, but also to reduce a risk of HIV infection spreading in general, so that one of the goals for international community fighting against HIV-spread is to maximize coverage of infected subjects with HAART. Antiretroviral therapy in HIV infection is administered lifelong, so that therapeutic efficacy may be lowered due to emergence of resistant HIV-1 variants. Currently, development of new antiretroviral drugs is currently underway throughout the world, therefore standard HIV-1 models are demanded to evaluate antiviral efficacy of promising drugs. To reliably assess drug efficiency regarding Russiawide HIV-1 variants, HIV-1 genovariants widespread in Russia should be used as a virus model. A recently emerged recombinant form of CRF63_02A6 HIV-1 is spread in Russia being currently a dominant variant detected among HIV-infected individuals in an extended region of the Siberian Federal District: in the Novosibirsk, Tomsk, Omsk, Kemerovo Regions, Krasnoyarsk and Altai Krai. We have obtained CRF63_02A6 infectious isolates of HIV-1, one of which contains mutations, reducing the sensitivity to the applied inhibitors of the virus reverse transcriptase. In addition, we constructed infectious molecular clones based on HIV-1 CRF63_02A6 variants with an affinity for CCR5 coreceptors and CXCR4. Infectious isolates and molecular clones CRF63_02A6 tested as models for assessing efficacy of antiretroviral drugs using the example of the drug “Efavirenz”. The fifty percent inhibitory concentration determined on the models of HIV-1 infectious molecular clones and HIV-1 isolate 18RU7056 ranged from 0.00027 pg/ml to 0.00046 pg/ml being in agreement with data published elsewhere. Concentrations of “Efavirenz” used in the study did not suppress the replication of HIV-1 12RU6987, which is resistant to non-nucleoside reverse transcriptase inhibitors, which confirms the decrease in the sensitivity of HIV-1 12RU6987 to “Efavirenz” by no less than 10,000 times. Thus, our data demonstrate that CRF63_02A6 HIV-1 isolated strains and infectious molecular clones are relevant and complementary tools for assessing efficacy of developing drugs aimed at suppressing HIV-1, including non-nucleoside-resistant virus reverse transcriptase inhibitors.

scholarly journals Nelfinavir and Non-Nucleoside Reverse Transcriptase Inhibitor-Based Salvage Regimes in Heavily Hiv Pretreated Patients

2003 ◽  
Vol 14 (4) ◽  
pp. 201-205 ◽  
Author(s):  
Jean-Guy Baril ◽  
Eric A Lefebvre ◽  
Richard G Lalonde ◽  
Stephen D Shafran ◽  
Brian Conway
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Salvage Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Retrospective Chart Review ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Rna ◽  
Cell Counts ◽  
Rna Levels

OBJECTIVE: To assess the efficacy of nelfinavir mesylate (NFV) in combination with delavirdine mesylate(DLV) or efavirenz (EFV) and other antiretroviral agents following virological failure on other protease inhibitor (PI)-based regimens.DESIGN: Multicentre, retrospective chart review.METHODS: One hundred-one patients who were naive to both NFV and non-nucleoside reverse transcriptase inhibitors (NNRTIs) and who initiated NFV plus DLV or EFV-based salvage regimens were reviewed. Response to treatmentwas defined as a reduction in HIV ribonucleic acid (RNA) levels to unquantifiable levels (less than 50 copies/mL, less than 400 copies/mL, less than 500 copies/mL) on at least one occasion after the initiation of salvage therapy. Baseline correlates of response, including prior duration of HIV infection, prior number of regimens, viral load and CD4 cell counts were also evaluated.RESULTS: Patients had a mean duration of HIV infection of 10 years, a mean duration of prior therapy of four years, a median of four prior nucleoside reverse transcriptase inhibitors and a median of two prior PIs. At the time of review the mean duration of salvage therapy was 63.4 weeks. Virological suppression was achieved in 59 (58.4%) patients within a mean of eight weeks and maintained for a mean of 44.9 weeks (themean follow-up was78 weeks). Of the non-responders, 16 (38%) achieved a less than 1 log10decrease in HIV RNA levels. Although there was no association between baseline correlates, response rate (75.7%) was significantly higher in patients with HIV RNA levels of 50,000 copies/mL or lower and CD4 counts greater than 200 cells/mm3.CONCLUSION: NFV/NNRTI-based highly active antiretroviral therapy regimens are an effective therapy in many patients who have experienced virological breakthroughs on at least one prior PI-based regimen.

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.

Complexity of Interactions Between Voriconazole and Antiretroviral Agents

2008 ◽  
Vol 42 (5) ◽  
pp. 698-703 ◽  
Author(s):  
Erin M Yakiwchuk ◽  
Michelle M Foisy ◽  
Christine A Hughes
Keyword(s):  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Product Information ◽  
Chronic Administration ◽  
Antiretroviral Drugs ◽  
Data Sources ◽  
Limited Information ◽  
Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Nonnucleoside Reverse Transcriptase Inhibitors

Objective: To evaluate and summarize pertinent aspects of the literature on interactions between voriconazole and antiretroviral agents. Data Sources: Primary literature was identified through MEDLINE (1950-February 2008), EMBASE (1988-February 2008), and International Pharmaceutical Abstracts (1970-February 2008) using the search terms voriconazole, ritonavir, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, raltegravir, maraviroc, and drug interactions. Additionally, relevant abstracts from infectious diseases and HIV conferences (2004-February 2008), reference citations from relevant publications, and product information monographs were reviewed. Study Selection And Data Abstraction: All articles identified from the data sources and published in English were reviewed. Of these, studies and reports addressing voriconazole pharmacokinetics or interactions with antiretroviral agents were evaluated. Data Synthesis: The interactions between voriconazole and antiretroviral drugs are complex. Voriconazole and ritonavir exhibit a time- and dose-dependent interaction. Ritonavir initially inhibits voriconazole metabolism, but, with chronic administration, subsequently induces voriconazole metabolism. This interaction is more pronounced with high doses of ritonavir. Coadministration of voriconazole and efavirenz at usual doses is contraindicated because of a 2-way interaction resulting in efavirenz toxicity and decreased therapeutic effect of voriconazole. Dosage adjustments of both drugs are required. Based on pharmacokinetic characteristics, interactions between voriconazole and other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (including etravirine), and maraviroc are likely but have not been well characterized in the literature. Interactions between voriconazole and nucleoside reverse transcriptase inhibitors or raltegravir are not anticipated. Conclusions: Interactions between voriconazole and antiretrovirals have the potential for serious consequences. However, because there is limited information available, further studies are warranted to establish these interactions and clarify their appropriate management. Until then, clinicians should be aware of the potential for interactions between voriconazole and antiretroviral agents and how to monitor for these interactions in clinical practice.

scholarly journals Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1263
Author(s):  
Ashley O. Otto ◽  
Christina G. Rivera ◽  
John D. Zeuli ◽  
Zelalem Temesgen
Keyword(s):  
Reverse Transcriptase ◽  
Adverse Reactions ◽  
Antiretroviral Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Entry Inhibitors ◽  
Clinical Literature ◽  
Contemporary Practice ◽  
Living With Hiv

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.

scholarly journals In VitroActivity of Antiretroviral Drugs against Plasmodium falciparum

2011 ◽  
Vol 55 (11) ◽  
pp. 5073-5077 ◽  
Author(s):  
Christian Nsanzabana ◽  
Philip J. Rosenthal
Keyword(s):  
Plasmodium Falciparum ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Antiretroviral Drugs ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Reverse Transcriptase Inhibitors

ABSTRACTMalaria and HIV infection are both very common in many developing countries. With the increasing availability of therapy for HIV infection, it was of interest to determine whether antiretroviral drugs exert antimalarial effects. We therefore tested thein vitroactivity of 19 antiretroviral drugs against the W2 and 3D7 strains ofPlasmodium falciparumat concentrations up to 50 μM. None of 5 tested nucleoside reverse transcriptase inhibitors demonstrated activity. Two nonnucleoside reverse transcriptase inhibitors, efavirenz (mean 50% inhibitory concentration [IC50] of 22 to 30 μM against the two strains) and etravirine (3.1 to 3.4 μM), were active; nevirapine was not active. Also active were the fusion inhibitor enfuvirtide (6.2 to 7.9 μM) and the entry inhibitor maraviroc (15 to 21 μM). Raltegravir was not active. However, for all active drugs mentioned above, the IC50s were considerably greater than the concentrations achieved with standard dosing. The effects most likely to be clinically relevant were with HIV protease inhibitors. Of the tested compounds, activity was seen with lopinavir (2.7 to 2.9 μM), atazanavir (3.3 to 13.0 μM), saquinavir (5.0 to 12.1 μM), nelfinavir (6.5 to 12.1 μM), ritonavir (9.5 to 10.9 μM), tipranavir (15.5 to 22.3 μM), and amprenavir (28.1 to 40.8) but not darunavir. Lopinavir was active at levels well below those achieved with standard dosing of coformulated lopinavir-ritonavir. Lopinavir also demonstrated modest synergy with the antimalarial lumefantrine (mean fractional inhibitory concentration index of 0.66 for W2 and 0.53 for 3D7). Prior data showed that lopinavir-ritonavir also extends the pharmacokinetic exposure of lumefantrine. Thus, when used to treat HIV infection, lopinavir-ritonavir may have clinically relevant antimalarial activity and also enhance the activity of antimalarials.

scholarly journals New Antiretroviral Therapies for Pediatric HIV Infection

2005 ◽  
Vol 10 (4) ◽  
pp. 215-247
Author(s):  
Jennifer L. Morris ◽  
Donna M. Kraus
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Pediatric Patients ◽  
Age Groups ◽  
Pediatric Hiv ◽  
Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Immunodeficiency Syndrome ◽  
Year 2000 ◽  
Hiv 1

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection.

Osteonecrosis of the knee in a patient receiving antiretroviral therapy

2002 ◽  
Vol 13 (11) ◽  
pp. 792-794 ◽  
Author(s):  
S H Allen ◽  
A L Moore ◽  
M J Tyrer ◽  
B J Holloway ◽  
M A Johnson
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Avascular Osteonecrosis ◽  
Antiretroviral Agents ◽  
Highly Active ◽  
The Right

A case of avascular osteonecrosis of the right knee is described in a patient with HIV infection. The patient had been receiving highly active antiretroviral therapy for two years prior to presentation. Osteonecrosis is an uncommon albeit serious complication of HIV infection and is associated with use of antiretroviral agents.

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