Replies to post #9134 on Cytodyn Inc (CYDY)

[jboatswain]

CCR5 is a major co-receptor for the HIV-1 virus;however, in humans, a 32-bp deletion results in a non-functional receptor protein that confers resistance to HIV-1 infection.This observation gave impetus to the development of small molecular weight antagonists and led to the approval of maraviroc,9 the first of a new class of virus entry inhibitors, for use in drug-resistant CCR5-tropic HIV-1 infection in 2007.

That's another detail about Maraviroc.

Competitive (pro 140) vs allosteric (Maraviroc): http://www.majordifferences.com/2013/02/difference-between-competitive.html

Despite this difference, it is good to understand how Maraviroc (MVC) develops resistance.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598208/

Resistance to MVC often occurs when previously undetectable X4-tropic HIV-1 are selected under pressure from drug treatment.25 This occurs when R5-tropic viruses, which previously constitute the majority of viral species, are sufficiently repressed. Viruses capable of using X4, which previously constituted a small minority, then multiply and become the dominant viral species

In 2007 maraviroc, a competitive CCR5 inhibitor, received clinical approval. Maraviroc is
representative of the new HIV drug class (entry inhibitors) that showed additional efficiency in ART
pretreated patients [40]. However, viral failure has been observed by re-emergence of X4-tropic viruses
with ongoing entry inhibitor use. This phenomenon was intensively studied and most studies found the
presence of even very small populations of non-CCR5 using strains of HIV before maraviroc initiation.
Evolutionary analysis revealed that X4-tropic viruses do not evolve de novo as a result of increased
selective pressure, but rather arise from pre-existing populations [41,42]. Therefore, X4-variants of HIV
can re-emerge if the R5 viral suppression is incomplete and/or the reservoir size of HIV has not been
suppressed to a critical level

Now put the above paragraphs in the context of this board's stance: screening can fix problems. Screening won't help PRO 140 if we consider this issue.

Has MVC increased the CCR5 density? I have no answer. Have HAART drugs increased CCR5 density? Some say, yes; some say, no. This is based on cursory reading.

http://jamanetwork.com/journals/jama/article-abstract/197929

Discontinuation of combined antiretroviral therapy (CART) improves virological control and specific immunity in some persons infected with human immunodeficiency virus 1 (HIV-1),1 whereas in others it results in rapid viral rebound and decrease in the antiviral cytotoxic T cell responses below the pretherapeutic level.2 The host factors responsible for these opposite consequences are largely unknown. We have recently reported that the mean number of CCR5 coreceptors at the surface of CD4 T cells (CCR5 density) is logarithmically correlated with viral load3 and disease progression4 during HIV-1 infection. We have explained this link by showing in vitro that CCR5 density strongly determines the efficiency of HIV-1 life cycle, particularly at the reverse transcription stage.5 Herein we report a test of the hypothesis that CCR5 density, which is stable over time in a given individual but varies among individuals, might determine the intensity of viral rebound after cessation of CART.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449250/

CCR5 density remained unchanged after highly active anti-retroviral therapy (HAART) introduction or cessation, whereas CD38 expression decreased and increased, respectively.