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.

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 HIV-2: an overview

2015 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
Mangala S. Borkar ◽  
Akshay A. Kashid
Keyword(s):  
Reverse Transcriptase ◽  
Opportunistic Infections ◽  
Well Being ◽  
Response To Treatment ◽  
Strand Transfer ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Hiv 1

HIV-2 is much less common compared to HIV-1, has to be confirmed by HIV-2 Western Blot test and is resistant to Efavirinz and Nevirapine. There are two HIV viruses, HIV-1 and HIV-2. HIV-2 is relatively rare in India. The clinical course of HIV-2 infection is slower, plasma HIV-2 RNA levels are lower as compared to HIV-1 infection, but once the illness progresses to AIDS, the course is similar to HIV-1. In few cases, there may be mixed infection with both HIV-1 and HIV-2,but the course of the illness is like in HIV-1 However ,even in mixed infections, one has to give the therapy as we would in isolated HIV-2 infection. In general it is accepted that therapy in cases of HIV-2 infection should be started before there is clinical progression. Studies recommend starting therapy when CD4 count drops below 500. HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors. Therapy in HIV-2 patients should include two nucleoside reverse transcriptase inhibitors plus an HIV-2 active boosted protease inhibitor or integrase strand transfer inhibitors. Monitoring of CD4 cell counts and clinical improvement should be used to assess response to treatment. Drugs used in Government ART centres in India under the umbrella of NACO are Tenofovir 300mg + Lamivudine 300 mg + Lopinavir 200 mg + Ritonavir 50 mg and are observed to be beneficial clinically in terms of weight gain, increase in CD4 levels ,prevention and control of opportunistic infections and improved sense of well-being.

HIV-1 Resistance Profile of the Novel Nucleoside Reverse Transcriptase Inhibitor β-D-2′,3′-Dideoxy-2′,3′-Didehydro-5-Fluorocytidine (Reverset™)

2003 ◽  
Vol 14 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Romas Geleziunas ◽  
Karen Gallagher ◽  
Hangchun Zhang ◽  
Lee Bacheler ◽  
Sena Garber ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Resistance Profile ◽  
Wide Range ◽  
Resistant Strains ◽  
Hiv 1

Nucleoside reverse transcriptase inhibitors (NRTIs) represent the cornerstone of highly active antiretroviral therapy when combined with non-nucleoside reverse transcriptase inhibitors (NNRTIs) or HIV-1 protease inhibitors (PIs). Unlike the NNRTIs and PIs, NRTIs must be successively phosphorylated by cellular kinases to a triphosphate form, which represents the active metabolite possessing antiviral activity. Emergence of viral resistance to NRTIs has severely hampered treatment options for persons infected with HIV-1. As such, there is an urgent need to develop NRTIs capable of suppressing NRTI-resistant strains of HIV-1. We have recently reported that the cytidine analogue D-d4FC (DPC817, Reverset™) effectively inhibits clinically prevalent resistant strains of HIV-1. In this report, we have extended these findings and now describe a detailed resistance profile for this novel NRTI. By examining a panel of 50 viruses carrying RTs derived from HIV-1 clinical isolates displaying a wide range of NRTI resistance mutations, we report that the median fold increase in effective antiviral concentration for such a panel of viruses is 3.2, which is comparable to tenofovir (2.8-fold) and didanosine (2.4-fold). D-d4FC is highly effective at inhibiting subsets of lamivudine-and zidovudine-resistant variants but, like other NRTIs, seems less potent against multi-NRTI-resistant viruses, particularly those carrying the Q151M complex of mutations. Finally, in vitro selections for HIV-1 mutants capable of replicating in the presence of D-d4FC yielded a mutant carrying the RT K65R mutation. This mutation confers 5.3- to 8.7-fold resistance to D-d4FC in vitro. These findings suggest that D-d4FC may represent an alternative NRTI for the treatment of individuals infected with lamivudine- and zidovudine-resistant strains of HIV-1.

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