antivirals used in autism inhibit HIV directly !!! what implications...

[Guest guest]

that is not through lowering overall viral load and freeing the immune

system, but through DIRECT inhibition of HIV virus (even though it is

not supposed to, it is a different type of virus, but heaps of studies

showing exactly that). ... meaning that all the treatments now

used in autism: chelation, valtrex, hbot, enzymes, raising glutathione,

herbs... ALL directly inhibit HIV. makes me wonder if all we doing right now in autism treatments is blindfold fighting a HIV-like virus?or

has

HIV mutated as to not be deadly to humans any more (as in simian

immunodeficiency virus, which is very deadly in some monkeys, but

relatively harmless in others - in monkeys that have had it for a while it "only" induces relatively milder form of immunosupression, regardless of absolutely massive viral loads in those monkeys )?

and has tricked our

immune systems into not producing antibodies - meaning it would be

impossible to detect by standard ELISA hiv test!!!

J Biol Chem.

2008 Nov 14;283(46):31289-93. Epub 2008 Sep 24.

The antiherpetic drug acyclovir inhibits HIV replication and selects

the V75I reverse transcriptase multidrug resistance mutation.

McMahon

MA et al. Department of Pharmacology and

Molecular Sciences, s Hopkins University

School of Medicine, Baltimore, land 21205, USA.

The antiviral drug acyclovir is a

guanosine nucleoside analog that potently inhibits herpes simplex virus (HSV)

replication. Acyclovir treatment in patients coinfected with HSV and human

immunodeficiency virus (HIV) has been observed to alter disease course and decrease HIV viral load, a finding that

has been attributed to indirect effects of HSV suppression on HIV replication.

Based on this hypothesis, several clinical studies have recently investigated

the use of acyclovir for treatment of patients coinfected with HSV and HIV or

for prophylaxis against HIV transmission. In this report, we use a single round

HIV infectivity assay to show that acyclovir directly inhibits HIV

infection with an IC50 of approximately 5 microm. The target of

acyclovir in HIV-infected cells is validated as HIV reverse transcriptase (RT)

by the emergence of the RT variant V75I under the selective pressure of

acyclovir. The V75I mutation is part of the multidrug resistance pathway that

enhances viral resistance to many of the best RT inhibitors approved for the

treatment of HIV. Biochemical analyses demonstrate that acyclovir triphosphate

is a chain terminator substrate for HIV RT and can compete with dGTP for

incorporation into DNA. Although acyclovir may prove a useful lead for

development of new HIV treatments, the selection of resistant mutants raises a

cautionary note to the use of acyclovir monotherapy in patients coinfected with

HSV and HIV. PMID: 18818198

Cell Host

Microbe. 2008 Sep 11;4(3):260-70.

Comment in:

Cell

Host Microbe. 2008 Sep 11;4(3):194-5.

Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in

herpesvirus-infected human tissues.

Lisco

A, et al.Eunice Kennedy Shriver National Institute of Child Health and

Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

For most viruses, there is a need

for antimicrobials that target unique viral molecular properties. Acyclovir

(ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA

polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress

other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human

tissues, but not in HHV-free tissue or cell cultures. However, addition of

HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity.

We hypothesized that such HIV suppression requires ACV phosphorylation by HHV

kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement

for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1

reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT

at the termination site. These data suggest that ACV anti-HIV-1 activity may

contribute to the response of HIV/HHV-coinfected patients to ACV treatment and

could guide strategies for the development of new HIV-1 RT inhibitors.PMID:

18779052

J Infect Dis.

2008 Dec 15;198(12):1804-8.

Herpes simplex virus (HSV)-suppressive therapy decreases plasma and

genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized,

placebo-controlled, cross-over trial.

Baeten

JM,et al.Department of Global Health, University of Washington,

Seattle, WA 98104, USA. jbaeten@...

A randomized cross-over trial of

herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg

twice daily, or placebo for 8 weeks, a 2-week washout period, then the

alternative therapy for 8 weeks) was conducted among 20 Peruvian women

coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who

were not on antiretroviral therapy. Plasma samples (obtained weekly) and

endocervical swab specimens (obtained thrice weekly) were collected for HIV-1

RNA polymerase chain reaction. Plasma HIV-1 level was

significantly lower during the valacyclovir arm, compared with the placebo arm

(-0.26 log10 copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1

level (-0.35 log10 copies/swab, a 55% decrease [P < .001]). Suppressive

HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1

disease progression.MID: 18928378

J

Infect Dis. 2007 Nov 15;196(10):1500-8. Epub 2007 Oct 31.

Herpes

simplex virus (HSV) suppression with valacyclovir reduces rectal and blood

plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized,

double-blind, placebo-controlled crossover trial.

Zuckerman

RA, et al Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. ccelum@...

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection

is common among human immunodeficiency virus (HIV)-infected persons, and HSV

reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels

during HSV suppression in coinfected persons in a placebo-controlled crossover

trial. METHODS: Twenty antiretroviral therapy (ART)-naive

HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell

counts >200 cells/ microL were randomized to receive either valacyclovir at

500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week

washout period and then received the alternative regimen for 8 weeks. Specimens

included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]),

thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR)

obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were

rectal and plasma HIV-1 RNA levels by treatment arm. RESULTS: HIV-1 was

detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected

in 29% and 4% of mucocutaneous specimens obtained during placebo and

valacyclovir administration, respectively (P<.001). Valacyclovir resulted in

a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10)

copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI,

0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1

level, compared with values for placebo. CONCLUSIONS: Valacyclovir

significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected

men. HSV suppression may provide clinical benefits to persons not receiving

highly active ART as well as public health benefits.PMID: 18008230

J Infect Dis.

2008 Dec 15;198(12):1804-8.

Herpes simplex virus (HSV)-suppressive therapy decreases plasma and

genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized,

placebo-controlled, cross-over trial.

Baeten

JM, et al

Department of Global Health, University of Washington,

Seattle, WA

98104, USA.

jbaeten@...

A randomized cross-over trial of

herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg

twice daily, or placebo for 8 weeks, a 2-week washout period, then the

alternative therapy for 8 weeks) was conducted among 20 Peruvian women

coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were

not on antiretroviral therapy. Plasma samples (obtained weekly) and

endocervical swab specimens (obtained thrice weekly) were collected for HIV-1

RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower

during the valacyclovir arm, compared with the placebo arm (-0.26 log10

copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1 level (-0.35

log10 copies/swab, a 55% decrease [P < .001]). Suppressive HSV-2 therapy has

the potential to reduce HIV-1 infectiousness and slow HIV-1 disease

progression. PMID: 18928378

J

Acquir Immune Defic Syndr. 2004 Apr 15;35(5):435-45.

The

effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a

review of two overlapping epidemics.

Corey

L, et al Department of Medicine, University of Washington Program in

Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA 98109,

USA. lcorey@...

Increasing evidence demonstrates a substantial link

between the epidemics of sexually transmitted HIV-1 and herpes simplex virus

(HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that

prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1

acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda

indicate that at all levels of plasma HIV-1 RNA in the source partner,

HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of

acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo

studies suggest that mucosal HIV-1 shedding is more frequent and in greater

amounts during mucocutaneous HSV-2 replication, including subclinical mucosal

reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most

experience frequent subclinical and clinical reactivations of HSV-2.

Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy

with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater

attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons

is warranted, especially those who continue to be sexually active, those not on

antiretroviral therapy, or those whose disease is not well suppressed by

antiretrovirals. PMID: 15021308

J

Infect Dis. 2002 Dec 15;186(12):1718-25. Epub 2002 Nov 22.

Changes

in plasma human immunodeficiency virus type 1 RNA associated with herpes

simplex virus reactivation and suppression.

Schacker

T, Department of Medicine, University

of Minnesota, Minneapolis,

55455, USA.

Schac008@...

In early trials of antiretroviral therapy, acyclovir was

associated with increased survival by an unknown mechanism. The hypothesis that

subclinical herpes simplex virus (HSV) reactivation was associated, in vivo,

with increased plasma human immunodeficiency virus (HIV) RNA and suppression

with a reduced plasma HIV RNA load was investigated. HSV cultures were

performed daily on HSV-2-positive/HIV-positive patients, and plasma HIV-1 RNA

loads were measured at regular intervals. A subset of patients prior to,

during, and after HSV suppression with high-dose acyclovir was measured to determine

whether HSV suppression was associated with a decrease in HIV replication. Most

(25/27 HSV-2-positive/HIV-positive persons) reactivated HSV. Total HSV shedding

rate was strongly correlated with plasma HIV-1 RNA load (R=0.54; P=.004), and the plasma HIV-1 RNA level

at a given CD4 cell count was 48% lower when treated with acyclovir.

These data indicate that frequent mucosal HSV reactivation influences HIV

replication in vivo and daily HSV suppression may be important in the

management of HSV-positive/HIV-positive persons. PMID: 12447756