HIV Damages and Sneaks Through

posted: 14/04/2010

HIV damages the cell walls of the genitals’ mucous membrane, and this lets HIV slip through to infect the vulnerable cells below, we have now learnt from a study. Most experts thought that HIV got through the mucous membrane itself, where these already had surface damage. This new scientific finding steers scientists who are creating microbicides and vaccines, to design these so they block contact between a very specific HIV protein and those in genital mucous membranes.

Microbicide hopes raised
This is an example of basic laboratory research into learning exactly how HIV attacks and works that may help solve a big HIV prevention problem. Women lack a HIV prevention method that they can control. Microbicides and vaccines are the best hope, but none have succeeded. This research gives microbicide and vaccine researchers a clear target to focus on. A few years down the line, we may see more hopeful signs of workable microbicides and vaccines appearing.

All sexual transmission of HIV occurs through mucous membranes. These researchers have basically found out that HIV has a protein that makes genital mucous membranes easier to pass through and cause infection. Previously researchers into HIV transmission had thought that transmission was most likely to occur either when the mucous membrane was damaged (for example through trauma or ulcers), or when many activated immune cells were present (such as during a sexually transmitted infection like gonorrhoea).

Disease progression?
The same ‘damage the cell walls and then sneak past’ strategy used by HIV for infecting people is thought by some experts to also help explain HIV disease progression and the development of some serious conditions, such as atherosclerosis (hardening and narrowing of the arteries).

How HIV does it
This study found that HIV weakens the integrity of surface cells, even when they are undamaged.

"It makes the electrical barrier resistance of epithelial cells decrease. By doing that, the virus can cross the barrier," said lead researcher Charu Kaushic, associate professor in the Centre for Gene Therapeutics at McMaster University, Ontario, Canada.

How does HIV actually get underneath epithelial cells to infect other cells that are susceptible to HIV? "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"

Aisha Nazli, a researcher in Kaushic's laboratory, noticed every time she put HIV on epithelial cells, their electrical resistance went down significantly. It happened every time she tried this.

Protein break through

Kaushic said the surface protein of the virus (the gp120 surface protein) causes the epithelial barrier to break. "The surface protein signals to the inside of the epithelial cells by binding to it", she said. "The epithelial cells start making inflammatory proteins which cause these cells to go on their self-destructive pathway."

The researchers say if viral load and exposure time are enough, HIV can probably disrupt any mucosal barrier in the body, although infection may not necessarily occur every time.

"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccines, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves," said Charu Kaushic.

Source

Nazli A et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathogens 6 (4): e1000852, 2010. (full article, free access)

Hepatitis C and HIV Outlook

posted: 18/11/2009

We can now say that having both hepatitis C and HIV doesn’t make it any more likely people will go on to develop an AIDS illness, but people do have a worsened chance of dying early.

One third higher risk of early death

A massive study of all the studies, a ‘meta-analysis’ of over 100,000 people has produced these findings. Since effective HIV treatment became available in the mid 1990s, co-infected people still have a 35% higher risk of death compared to people with just HIV.

The investigators believe that that “the major contributor to mortality among co-infected subjects during the HAART [highly active antiretroviral therapy] era is likely to be liver disease.”

HIV treatments mean that many people with HIV can look forward to a long and healthy life. However, the outlook for people with both HIV and hepatitis C is significantly shorter than for people who only have HIV.

Indeed, liver-related disease is now an important cause of death in HIV/hepatitis co-infected patients. Although there is a lot of evidence showing that HIV accelerates the course of hepatitis C disease, there is less agreement about the effect of hepatitis C on HIV disease progression.

A team of US investigators therefore conducted a meta-analysis of 37 studies published before April 2008 to see what impact hepatitis C had on HIV disease progression and overall mortality.

Before HIV treatments experience
Ten of the studies were before effective antiretroviral therapy became available. These studies showed that before HIV treatment became available, people with both HIV and hep C were slightly less likely to face worsening HIV than people who only had HIV – not a worsening in HIV health as you might have expected.
This part of the analysis had 4413 people with both hep C and HIV and 10,213 individuals who only had HIV.

After HIV treatments
They then looked at studies after 1996 when modern HIV treatments became available. This part of the analysis had 25,319 people with both hep C and HIV and 61,697 people with only HIV. These showed that people with both hep C and HIV were 35% more likely to die early compared with people who only have HIV.

Older, on treatment, how long with hep C
People with both hep C and HIV who were older, or taking antiretroviral therapy had an especially higher risk of death.

Moreover, the longer someone has both hep C and HIV, then the greater the risk of earlier death.

End outcome
The results from the meta-analysis depend on whether you stop the clock when people get AIDS, or follow people until they die. If you stopped the clock at an AIDS diagnosis, then the results show there is no difference between people who only have HIV and those with hep C as well. But in life, none of us have time machines that can prevent our dying. Therefore we should pay more attention to the 36% higher risk of dying early with hep C.

Seven studies in the meta analysis looked at how hep C and HIV affected disease progression, whether this was defined as either an AIDS diagnosis or death. Co-infected people were 49% more likely to get AIDS or die early than people who only have HIV..

Liver disease likely killer
“The majority contributor to mortality among co-infected subjects during the HAART (highly active antiretroviral therapy) era is likely to be liver disease”, comment the investigators. “The meta-analysis did not demonstrate increased risks of developing AIDS-defining events among co-infected patients”, conclude the investigators.
 

What next?
They recommend that “future studies that attempt to examine mortality among coinfected subjects should attempt to determine the relative contributions of hepatitis C viremia as a surrogate marker for liver disease risk, whether injecting drug use is current…, and whether broader application of hepatitis C treatment positively impacts mortality in co-infected individuals.”

Source

Chen T-Y et al. Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression. Clin Infect Dis 49 (10): 1605-1615, 2009.

photo credit and hepatitis c gene quilt panel 

Hepatitis C - Blood Blamed

posted: 13/11/2009

Contact with blood, not semen, is how hepatitis C is being passed on among some gay men living with with HIV. This is what is now being reported at the European HIV conference underway in Cologne, Germany.

Fisting, group sex, and snorting drugs emerged early on as significant risk factors for sexual transmission of hepatitis C. But unprotected anal sex on its own, without fisting, parties and snorting drugs, doesn't seem to transmit hepatitis C. 

The investigators believe we should refocusing hepatitis C prevention campaigns for HIV-infected gay men from warning about unprotected sex to warning about transmission, probably through tiny, usually invisible, droplets of blood.

Since 2000 outbreaks of sexually transmitted hepatitis C have been reported amongst HIV-positive gay men in a number of large northern European cities including London, Amsterdam and Berlin. Unprotected anal sex and fisting were quickly identified as risk factors.

Semen or Blood?

But is hepatitis C transmitted through the semen (like HIV), or through blood in these encounters?

Because men living with HIV have a higher hepatitis C viral load in semen than men without HIV, this could explain the higher rates of hepatitis C among HIV positive gay men. But HIV-negative partners (of gay men with both HIV and hepatitis C) almost never get heptaitis C, so it looks like it isn't transmitted through semen. HIV-positive heterosexual couples where one partner also have hepatitis C don't infect each other either. This points strongly to blood, not semen, as the means of hepatits C transmission among HIV+ gay men.

Positive gay men in Bonn

Investigators in Bonn did a case-controlled study involving 34 gay men with both HIV and hepatitis C, and 67 age-matched men who only had HIV. None of the men reported injecting drug use.

The men were recruited to the study between 2006 and 2008. They provided information on their sexual and drug use behaviour, and also stated if they had experienced rectal bleeding as a consequence of sex.

Unprotected anal sex was widely reported, and approximately 50% of men reported receptive fisting.

So how does the blood get transmitted?

The first set of statistical analysis showed that several risk factors were associated with infection with hepatitis C including

• use of sex toys
• rectal bleeding
• receptive fisting without gloves
• sharing and snorting stimulant drugs like cocaine and amphetamine during group sex.

Only these three things were clearly linked to heptatits C transmission when they did a more detailed multivariate analysis:

• receptive fisting 
• rectal bleeding 
• drug use during group sex.

So the researchers propose hepatitis C is being transmitted via blood rather than semen, and that even men without hepatatis C can be involved in a transmission chain, during group sex sessions.

Some disagreement

However, not all delegates at the conference were convinced. A questioner from the floor pointed out that many HIV-positive people with acute hepatitis C infection in London do not report fisting.

Moreover, Dr Sanjay Bhagani told aidsmap that it was his sense that the epidemiology of hepatitis C amongst HIV-positive gay men in London was changing and that many infections could probably be attributed to injecting drug use rather than sex.

In addition, HCV itself is sometimes found in semen, and men who have both HIV and HCV tend to have HCV in their semen more often than men who have HCV but not HIV, according to a report from Canadian AIDS Treatment Information Exchange.

Nevertheless, the investigators conclude that prevention messages should inform HIV-positive gay men of the risks of hepatitis C that arise from long-lasting, group-sex sessions where there is rectal trauma caused by activities such as fisting. The blood may not be visible - microscopic amounts are enough - hepatitis C is vastly easier to pass on than HIV.

Source with more details and reference

Hope with 3rd Drug to Treat Hepatits C

posted: 10/11/2009

Adding a new hepatitis C protease inhibitor to existing treatments for hepatitis C led to a 'cure' for 80% of people who just have hepatitis C, a new study C has shown.

Trials are now starting on whether adding this extra drug will also work for people who also have HIV. These trials were delayed because of concerns about interactions between this new hepatitis C protease inhibitor, telaprevir, and anti-HIV drugs.

The patients in the study had hepatitis C genotype 1 infection – one of the harder-to-treat strains of hepatitis C.
 

Many people with HIV are also infected with hepatitis C (co-infection), and liver disease caused by hepatitis C is now a significant cause of death for people with the two infections.
 

Treatment for hepatitis C is with both pegylated interferon and ribavirin. Treatment normally lasts for a year, and can cause unpleasant side-effects. The aim is a 'cure'. This type of 'cure' means having an undetectable hepatitis C viral load six months after treatment has been completed.
 

Best hope for hepatitis C treatment with HIV is to start as soon as possible

Patients who start treatment soon after they are infected with hepatitis C have the best chance of this outcome. If you have already had hepatits C for some time, the 'cure' rate with the current two-drug treatment for a year falls to about one third of people living with HIV.
 

But new anti-hepatitis C drugs are in development, such as a protease inhibitor called telaprevir. It’s been investigated in studies where it’s used in combination with existing treatment. The new study has shown that when these three drugs were used, over 80% of patients who were only infected with hepatitis C were cured of their infection.
 

Studies looking at the safety and effectiveness of newer treatments for hepatitis C are only just starting in people with HIV. These studies have been delayed because of concerns about interactions with anti-HIV drugs.
 

More about hepatitis C treatment with HIV

The July edition of HIV Treatment Update included a feature 'Combinations and conundrums: the challenges of hepatitis C treatment'. Download it
You can subscribe to HIV Treatment Update via NAM's online bookshop, or email NAM  or ring 020 7840 0050. Subscriptions are free for people living with HIV in the UK.
 

Source

Read more about hepatitis C treatment with HIV in the Combinations and Conundrums article in HIV Treatment Update July 2009 pages 8-11 
 

Hep C - relapsed or reinfected?

posted: 29/10/2009

About a third of HIV-positive people who have both hepatitis C and HIV relapse (become ill again) after being treated for hepatitis C. Gay men and people who have ever injected drugs are more likely to have hepatitis C than other people with HIV.

Cure possible, but different strains, relapses and reinfections

Unlike HIV, hepatitis C can be cured. It is treated with two drugs taken together, pegylated interferon and ribavirin. How long you need treatment for depends on which strain of hepatitis C you have. If you have the harder-to-treat genotypes 1 and 4, you need 48 weeks of treatment, but people with genotypes 2 and 3 usually have half this - 24 weeks treatment.
 

Undetectable hepatitis viral load?

Hepatitis C treatment aims for an undetectable hepatitis C viral load. There are two checks to see if it has worked, once at the end of treatment, and 6 months after treatment ended. If hepatitis is still undetectable after 6 months they call this a sustained virological response, and this is considered to be a cure.

1 in 3 success for people with HIV, but a relapse awaits 1 in 3
But only about a third of people with HIV who have had hepatitis C for a while are 'cured' in this way(a cure is more likely if you start hepatitis treatment soon after getting hepatitis C).

But now researchers have found that about a third of the people who are ‘cured’ of hepatitis C after 6 months find hepatitis C reappears later – they have a relapse. People without HIV, but with hepatitis C don’t normally have this relapse problem.

Researchers checked to see if people had really relapsed or whether they had got hepatitis C from someone else. Nearly all the people had a genuine relapse, although two seem to have been reinfected. But we know from a study in London that many HIV-positive gay men who have a hepatitis C ‘relapse’ had in fact been reinfected.

Reinfection a common risk
In the London study which looked at relapsing gay men, of 211 HIV/hepatitis C coinfected men, 16 got hepatitis C again after successful treatment. Looking at the relapsing men, almost all had yet another sexually transmitted infection at the same time - usually syphilis (ten cases), but also gonorrhoea (six cases) and herpes (three cases).

Last year, Dr Mark Nelson, of the Chelsea & Westminster told the August/September issue of HTU Treatment Update that he finds syphilis and lymphogranuloma venereum (LGV) in many of his patients with hepatitis C, and both of them “make HIV and hepatitis C transmission even more likely.”

Positive gay men need better information

He added that the continued sexual transmission of hepatitis C amongst HIV-positive men “underlines the importance of safer sex messages for HIV-positive men. Some men are having condomless sex because they think that they won’t pass on HIV to someone who already has HIV, or if they have an ‘undetectable’ viral load for HIV, they can’t pass on HIV to anyone. But it does seem they’re passing on—and getting—hepatitis C.”

Dr Jones suggests that healthcare providers are “failing our patients,” since they are becoming infected with hepatitis C not once, but multiple times. Since the paper was published two of the men who had been treated for a second episode of acute hepatitis C had become reinfected for a third time. “We need a much stronger public health information and screening programme” for hepatitis C, she said.

Source aidsmap