Which classes of antiviral drugs still highly effective in the case of HIV virus?
Nucleoside reverse transcriptase inhibitors (NRTI) and nucleotide reverse transcriptase inhibitors (NtRTI)
Dear Pals ,
Effectiveness of drug also depends upon the stage of HIV .Generally NTRI should work
Regards
Aamir Javed
The first effective therapy against HIV was the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine (AZT).
Broadly, there are five classes of drugs, which are usually used in combination, to treat HIV infection. Use of these drugs in combination can be termed anti-retroviral therapy (ART), combination anti-retroviral therapy (cART) or highly active anti-retroviral therapy (HAART).
Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. Maraviroc and enfuvirtide are the two currently available agents in this class.
Nucleoside reverse transcriptase inhibitors (NRTI) and nucleotide reverse transcriptase inhibitors (NtRTI) are nucleoside and nucleotide analogues which inhibit reverse transcription. Examples of currently used NRTIs include zidovudine, abacavir, lamivudine,emtricitabine, and tenofovir.
Non-Nucleoside reverse transcriptase inhibitors (NNRTI) inhibit reverse transcriptase by binding to an allosteric site of the enzyme; NNRTIs act as non-competitive inhibitorsof reverse transcriptase. NNRTIs affect the handling of substrate (nucleotides) by reverse transcriptase by binding near the active site. NNRTIs can be further classified into 1st generation and 2nd generation NNRTIs. 1st generation NNRTIs include nevirapine and efavirenz. 2nd generation NNRTIs are etravirine and rilpivirine. HIV-2 is naturally resistant to NNRTIs.
Integrase inhibitors (also known as integrase nuclear strand transfer inhibitors or INSTIs) inhibit the viral enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. Raltegravir has two metal binding groups that compete for substrate with two Mg2+ ions at the metal binding site of integrase. As of early 2014, two other clinically approved integrase inhibitors are elvitegravir and dolutegravir.
Protease inhibitors block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane. Examples of HIV protease inhibitors are Lopinavir, Indinavir, Nelfinavir, Amprenavir and Ritonavir. Darunavir and atazanavir are currently recommended as first line therapy choices.[4]Maturation inhibitors have a similar effect by binding to gag, but development of two experimental drugs in this class, Bevirimat and Vivecon, was halted in 2010.
It would depend on the genotype of the patient's HIV. Depending on where you practice, the rate of baseline resistance will vary.
In the US, current guidelines recommend using either a NRTI backbone along with either an integrase inhibitor or a protease inhibitor. Preferred regimens are:
Integrase Strand Transfer Inhibitor-Based Regimens:
• Dolutegravir/abacavir/lamivudine (only for patients who are HLA-B*5701 negative (AI)
• Dolutegravir plus tenofovir disoproxil fumarate (tenofovir)/emtricitabine (AI)
• Elvitegravir/cobicistat/tenofovir/emtricitabine (only for patients with pre-antiretroviral therapy CrCl >70 mL/min) (AI)
• Raltegravir plus tenofovir/emtricitabine (AI)
Protease Inhibitor-Based Regimen:
• Darunavir/ritonavir plus tenofovir/emtricitabine (AI)
Please note that the combination tenofovir/emtricitabine/efavirenz is no longer considered a preferred regimen due to possible Central Nervous System side effects with the efavirenz.
Regards,
Paul Anthony
Drug efficacy as Paul Anthony mentioned is dependent on a patients resistance profile. There are other factors that the US guidelines committee has been factoring into decisions on preferred regimens that we sometimes overlook but play a major role in the clinical setting.
Medication tolerability is very important considering the fact that most patients would be on drugs for a significant length of time. If you go bakwards in history there has been many different medications specifically in the NRTI class that I would say have fallen by the wayside. These drugs are no longer used in the US and even in some developing worls setting because of the side-effects they cause maily lypodystrophy and peripheral neuropathy mostly from mitochondrial toxicity.
The integrase inhibitors as a class have both proven efficcay and rather low toxicity. The rapid viral decay that is seen when these drugs are used actually makes the development of resistance less likely even in moderately compliant patients. Most of us clinicians are choosing regimens based on our projections on the adherence of our patients as well how likely they are to develop side-effects. We also consider who is more likely to stop medications because of some minor side-effect.
Your question though very valid has no good answer in the real life clinical setting.
Dear Sir,
I send to you this link I think Helpful.
https://www.aids.gov/hiv...hiv.../treatment.../overview...
The contribution of NRTIs to highly effective long-term HIV suppression is, at least in part, due to their synergistic effects in combination with other class of antiretrovirals. In addition, intracellular accumulation and prolonged retention of active metabolites of some NRTIs allowing for their once-daily dosing is more forgiving towards non-adherence and can buffer the pharmacokinetic fluctuations in levels of other drugs in any given regimen. Because of these unique properties, NRTIs are likely to remain, at least in the near future, the backbone of most drug combinations for the treatment of both naïve and experienced patients.
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