--- Quote from: life2 on August 16, 2013, 11:07:07 pm ---Definitely is and it's not just an issue for those with hiv. It's a global issue involving antibiotic resistant bacteria like MRSA as well. (I've personally won this lottery :() In the case of hiv we know it naturally has a high rate of mutation. It's a tricky bastard. One way to reduce the amount of mutations created is by keeping the viral load as low as possible through HAART. The interesting question is if/how the presence of HAART drugs affect the rate or variation of mutation? ote
I would imagine the probability of a mutation that renders the virus less fit is much much much higher than one that renders it more fit. However, what is happening during the reverse transcriptase step and what is integrated are TWO VERY DIFFERENT STEPS. What is integrated is the transcript that will be transcribed ALWAYS! However when things are reverse transcribed into DNA to new cells, most mutations like said above probably render the virus useless but the one that makes it more fit will make it to integration. You would think that with all the antibodies and the drugs in the bloodstream would prevent this copy from integrating preventing any resistance issues. Even having a resistant strain come into your system while on treatment should not be an issue because the antibodies should neutralize this strain. I think this is supported with evidence that reinfection is highly unlikely and there have been a few cases reported. --- End quote ---
Mishma:
Not so confusing, maybe a tad alarmist.
Remember folks, HIV inhabits reservoirs (brain/testes) that are beyond the reach of HAART. Even in those of us who have undetectable virus in our plasma still have actively replicating viruses within our bodies.
Rare mutations that increase the fitness (or reproductive success) of a virus may have either deleterious or rarely confer on it an advantage: Disadvantage 1) a mutation that increases virulence and kills off the host quickly would in time reduce the number of new infections (think the Ebola and Marburg viruses 2) a mutation in HIV that restores the host's ability to fight it (restoring IFN and apoptosis pathways) would also be disadvantageous.
Advantage: 1) drug resistance. Some folks (a minority) are just not "fit," enough to fight the virus, even with the aid of HAART. The viruses wins in the short run in this scenario but loses the war.
The bottom line, in my opinion, is viral persistence and the ongoing low-level chronic inflammation that we endure are more to be feared then the classic "superinfection," scenario-which has never materialized.
mecch:
--- Quote from: Mishma on August 19, 2013, 05:34:40 pm --- Advantage: 1) drug resistance. Some folks (a minority) are just not "fit," enough to fight the virus, even with the aid of HAART. The viruses wins in the short run in this scenario but loses the war.
--- End quote ---
Please show statistics. Please elaborate what a "minority" is. Please tell me about people, say infected within the last 10 years, on HAART at the appropriate time, and adherent - who were not "fit" and died of AIDS, cause all 2nd, 3rd, and salvage therapies useless. Hmmmm?????
Mishma:
There are lies, damn lies and then there are statistics. Basic common sense here my friend. Antivirals and antibiotics only supplement our own immune responses to the various pathogens-they are not the cure all for everyone-nor has HAART alone eradicated the virus from anyone who has been infected any significant period of time.
I agree that perfect adherence and salvage therapies for those who have been diagnosed and treated early in their disease course will do a lot better in the long run than those of us who started with either nothing or AZT. Plus, studies have shown that the longer individuals stay virally suppressed the less likely they are to rebound. But I digress you wanted facts:
http://www.ncbi.nlm.nih.gov/pubmed/17450401
Bull Math Biol. 2007 Aug;69(6):2027-60. Epub 2007 Apr 21. Emergence of HIV-1 drug resistance during antiretroviral treatment. Rong L, Feng Z, Perelson AS. Source Department of Mathematics, Purdue University, West Lafayette, IN 47907, USA. Abstract Treating HIV-infected patients with a combination of several antiretroviral drugs usually contributes to a substantial decline in viral load and an increase in CD4(+) T cells. However, continuing viral replication in the presence of drug therapy can lead to the emergence of drug-resistant virus variants, which subsequently results in incomplete viral suppression and a greater risk of disease progression. In this paper, we use a simple mathematical model to study the mechanism of the emergence of drug resistance during therapy. The model includes two viral strains: wild-type and drug-resistant. The wild-type strain can mutate and become drug-resistant during the process of reverse transcription. The reproductive ratio [Symbol: see text](0) for each strain is obtained and stability results of the steady states are given. We show that drug-resistant virus is more likely to arise when, in the presence of antiretroviral treatment, the reproductive ratios of both strains are close. The wild-type virus can be suppressed even when the reproductive ratio of this strain is greater than 1. A pharmacokinetic model including blood and cell compartments is employed to estimate the drug efficacies of both the wild-type and the drug-resistant strains. We investigate how time-varying drug efficacy (due to the drug dosing schedule and suboptimal adherence) affects the antiviral response, particularly the emergence of drug resistance. Simulation results suggest that perfect adherence to regimen protocol will well suppress the viral load of the wild-type strain while drug-resistant variants develop slowly. However, intermediate levels of adherence may result in the dominance of the drug-resistant virus several months after the initiation of therapy. When more doses of drugs are missed, the failure of suppression of the wild-type virus will be observed, accompanied by a relatively slow increase in the drug-resistant viral load.
mecch:
--- Quote from: Mishma on August 20, 2013, 12:00:00 pm --- Simulation results suggest that perfect adherence to regimen protocol will well suppress the viral load of the wild-type strain while drug-resistant variants develop slowly. However, intermediate levels of adherence may result in the dominance of the drug-resistant virus several months after the initiation of therapy. When more doses of drugs are missed, the failure of suppression of the wild-type virus will be observed, accompanied by a relatively slow increase in the drug-resistant viral load.
--- End quote ---
Still drumming my fingers, still waiting for statistics, field reports, actual studies of these few people who are are "just not "fit," enough to fight the virus, even with the aid of HAART."