Sacrifice bunt to left field: Tiny kinda sorta win for anti-HIV-1 therapies

Last week I wrote about a disappointing study where they found that treating people infected with HIV-1 and HSV-2 with acyclovir didnt decrease their rates of HIV-1 transmission to their partners... even though they had lower HIV-1 viral loads, and fewer HSV-2 outbreaks.

Really disappointing.

Well, that same group reanalyzed their data from a different angle: The people who got acyclovir, how did that effect their progression to AIDS?

Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial--
Our results show that standard doses of aciclovir for suppression of herpes simplex virus type 2 in people infected with HIV-1 and herpes type 2 reduced the risk of HIV-1 disease progression by 16%. Fewer participants in the aciclovir group than in the placebo group had CD4 cell counts fall below 200 cells per μL (p=0·06), started antiretroviral therapy (p=0·05), or died from non-trauma-related reasons (p=0·29). Furthermore, fewer of those in the group assigned aciclovir with counts of 350 cells per μL or higher had counts fall below this concentration than did those in the placebo group (p=0·002).

This is only 'meh' news, in that this only works on people who are dually infected with HIV-1 and HSV-2. And acyclovir isnt reliably stopping progression to AIDS-- lots of people in the acyclovir group had to go on real antiretrovirals, just like the people who got placebo... just fewer of them.

BUT, this is good news, too, cause acyclovir is NOT directly acting on HIV-1. Its just stopping the unhelpful partnership between HIV-1 and HSV-2. Thus HIV-1 has no conceivable way of 'mutating' to restart that partnership. Its not really a job it is prepared to do, it was just taking advantage of a useful situation. We know this, because that drop in HIV-1 viral load in HSV-2 patients taking acyclovir? The HIV-1 load stayed down for two years (the length of the study). If you give someone with HIV-1 one antiretroviral, viral load would go down, but then it would pop back up when drug resistant variants regained fitness.

Summary: HIV-1 and HSV-2 infected patients have higher HIV-1 viral loads than people infected with HIV-1 only, because HSV-2 codes for proteins HIV-1 finds useful. Acyclovir, a drug that stops HSV-2, also stops HIV-1 piggy-backing on HSV-2.

Thus HIV-1/HSV-2 positive patients who are on acyclovir have lower viral loads and delayed HIV-1 disease progression a little bit, but does not stop their ability to transmit HIV-1, at all.

Because 70-90% of HIV-1 positive individuals are also HSV positive, and because lots of people still dont have access to HAART, and because acyclovir is (relatively) pretty cheap, acyclovir could extend the lives of some infected folks until we get a better plan.

Tiny wins, thats all Im asking for now.

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But I guess that's really what most of the advances in science and technology are made up of -- incremental improvements, gained at the cost of a lot of hard work, frustration, and disappointment.

Hollywood likes the big, dramatic stuff, of course, and those are the stories that sell -- perhaps because they're the only ones that the public understands, or perhaps because they're the only stories that Hollywood sells.

But I suspect that every big, dramatic breakthrough was preceded by long years, decades, or centuries of incremental gains -- it may take only a moment to ask the question that leads to a breakthrough, but to reach the point where it's possible to figure out what question to ask? That can take generations.

So it's an incremental gain, but even if it gives us just a few meters of new ground, it's good -- and it may yet, by whatver it leads to, directly or indirectly, be better than we know.

By TotallyUncool (not verified) on 17 Feb 2010 #permalink