New drug approved
A drug from a completely new class of antiretrovirals has been approved in the US. It is called maraviroc (its trade-name in the US is Selzentry, but will be called Celsentri in the UK and Europe). Maraviroc belongs to a class of anti-HIV drugs called CCR5 inhibitors and it works by preventing HIV from attaching itself to something called the CCR5 co-receptor on the surface of immune system cells. This means that HIV is prevented from infecting cells. All the currently available oral anti-HIV drugs work against HIV once it has entered a cell.
Maraviroc has been approved for use by people who have taken a lot of anti-HIV drugs in the past and who have something called CCR5-tropic HIV (this can be checked for using a special test).
Studies during the development of maraviroc showed that highly treatment-experienced people who received maraviroc with a combination of anti-HIV drugs selected by resistance tests (a so called, optimised background of drugs) were much more likely to get their viral load below 400 copies/ml and 50 copies/ml than those who just took the optimised background with a placebo.
A study presented to the recent International AIDS Society conference in Sydney showed that the best results were seen when maraviroc was combined with at least one drug that HIV was not resistant to.
Maraviroc is expected to be granted formal approval in Europe this autumn. In the meantime, people who would benefit from treatment with maraviroc can get the drug through an expanded access scheme. Click here for details.
Atazanavir for people new to HIV treatment
Atazanavir (Reyataz) is a protease inhibitor that is currently only recommended in Europe for use by people who have taken anti-HIV drugs before. Atazanavir’s potency can be boosted by taking it with a small dose of an other protease inhibitor, ritonavir (Norvir).
But the study did find that people who took atazanavir boosted by ritonavir were slightly more likely to have an undetectable viral load after two years. What’s more, they were also less likely to develop drug-resistant HIV.
Atazanavir can cause a harmless, but nevertheless distressing, yellowing of the skin. This is because the drug can cause levels of bilirubin, which is produced by the liver, to build up. In the study, five of the people taking boosted atazanavir stopped treatment because of yellowing of the skin (hyperbiliruninaemia) compared to none of the people taking the unboosted drug.
HIV treatment for older patients
Potent anti-HIV treatment can mean a longer, healthier life. Indeed, doctors are now optimistic that a person who is diagnosed with HIV before the virus has done too much damage to their immune system, who also receives appropriate HIV therapy, and who take their treatment properly, will live a more or less normal lifespan.
But studies looking at the prognosis of people receiving HIV treatment have tended to focus on younger patients and there is less certainty about the effectiveness of HIV treatment in older patients. For the purposes of studies, older patients are usually classified as the over-50s.
The French researchers did however find that the over-50s were more likely than the under-50s to change their first anti-HIV combination because of side-effects. They also found that older patients were more likely to experience certain side-effects, including neuro-psychiatric side-effects and blood disorders.
Late diagnosis is one of the main reasons why people with HIV still become ill or even die. The French researchers found that late diagnosis was the main reason why people in their study didn’t do well on HIV treatment, and that older patients were much more likely to have their HIV diagnosed late than younger patients.
Monitoring HIV
There are two key tests used to monitor the health of people with HIV. A CD4 cell count is used to check the state of the immune system. A CD4 cell count of above 500 is considered normal, a CD4 cell count of around 350 shows that moderate damage to the immune system has been sustained and that thought should be given to starting anti-HIV treatment, and a CD4 cell count of 200 shows that a person is vulnerable to potentially fatal infections and should start HIV treatment. A viral load test is used to monitor the rate of HIV replication. The goal of anti-HIV treatment is an undetectable viral load.
The state of the immune system can also be checked by looking at the percentage of CD4 cells. A CD4 cell percentage of 28% or above is considered normal, and a CD4 cell percentage of 14% is the equivalent to a CD4 cell count of 200.
A study recently showed that HIV-negative people with cirrhosis often had low CD4 cell counts but normal CD4 cell percentages. This led a researcher to suggest that this might also be the case in people with HIV who have cirrhosis. If correct, this theory could have had important implications meaning, for example, that decisions about the best time to start HIV treatment should be guided by CD4 cell percentage and not CD4 cell count.
But Italian researchers have now shown that this is not the case. They found that for all HIV-positive patients, regardless of the state of their immune system or whether or not they had cirrhosis, a CD4 cell count and not a measure of CD4 cell percentage was the best way of predicting somebody’s risk of HIV disease progression.
HIV and cancer
Since effective anti-HIV treatment became available, the AIDS-defining cancers non-Hodgkin’s lymphoma and Kaposi’s sarcoma have become much rarer. But there is some evidence to suggest that, even with potent antiretroviral treatment, people with HIV are more likely than those in the general population to develop certain cancers that aren’t normally considered to be related to HIV. Often these cancers are linked to other infections, such as anal and cervical cancer that are caused by certain strains of the genital wart virus, HPV.
Research recently represented to the International AIDS Society Conference in Sydney provided further evidence that people with HIV are more likely than their HIV-negative peer to develop some cancers. This US study showed that although both non-Hodgkin’s lymphoma and Kaposi’s sarcoma were now much less common in people with HIV, people with HIV were more likely than the general population to develop anal cancer, Hodgkin’s lymphoma, liver cancer, lung cancer, melanoma and cancers of the mouth and throat. The researchers also found that colorectal cancer was becoming more common in people with HIV.
Inline with the findings of other studies, many of these cancers are related to infections. HPV has been associated not only with anal cancer, but with oral and throat cancer too, and the risk of liver cancer is particularly high in people with hepatitis B or C.
The doctors suggest that the rates of many of these cancers could be cut if anti-smoking messages to conveyed to people with HIV, and if there was screening for colorectal cancer. They also called for more work to determine the effectiveness of using Pap smears to identify people with a risk of anal cancer.
HPV vaccine and gay men
A vaccine has recently become available that provides very good protection against the strains of HPV most associated with cervical (and anal) cancer. But it is known that the vaccine doesn’t work if a person is already infected with the strains of HPV it is designed to protect against. Nor has the safety and effectiveness of the vaccine been tested in men, or in people with HIV.
They found that approximately 40% of HIV-positive men in their study, which was conducted in the USA, were infected with the cancer-causing HPV-16 and/or HPV-18 strains. They believe that this figure justifies widespread vaccination as it could prevent many cases of anal cancer.
Their study also found that using both Pap smear tests and HPV DNA tests would help diagnose more cases of HPV than reliance on either test alone.
But another recent study on HPV vaccination found that there was absolutely no value providing the vaccine to women who were already infected with HIV. The study was conducted in Costa Rica and included women infected with HPV-16/18. It compared clearance of HPV-16/18 in women who were given a recently-developed HPV vaccine to clearance of the virus in a control population of women. Women in both arms of the study were equally likely to clear HPV-16/18 infection. The researchers concluded that there was no value providing HPV vaccination to women who were already infected with HPV-16/18.
HIV-positive gay men and the sexual transmission of hepatitis C
Over the past five or so years, doctors across north-western Europe have noticed new cases of hepatitis C virus in HIV-positive gay men. Hepatitis C is usually spread by contact with infected blood and injecting drug use is a particular risk factor, but these men only had sex as a risk factor for their hepatitis C infection.
Several risk factors have been identified for the sexual transmission of hepatitis C, one of which is unprotected anal sex. Other risk factors are group sex, fisting, and drug use.
Studies looking at the sexual transmission of hepatitis C in heterosexual couples where one is hepatitis C-infected and in HIV-negative gay men have failed to find any real evidence that the virus is sexually transmitted.
One study found that hepatitis C viral load is higher in the semen of men with HIV, possibly explaining why HIV-positive gay men are at greater risk of the infection. But some researchers think that other factors are involved.
And a German study presented to the recent Sydney conference seems to show this. It found that although unprotected anal sex was one of the risk activities which HIV-positive gay men with recent hepatitis C infection had, it could not, on its own explain their hepatitis C infection.
The study found that rectal trauma, group sex and drug use were the most important risk factors. They think that bleeding or inflammation resulting from long sex sessions, involving multiple partners, plus the mood-affecting or pain-killing effects of drugs, were leaving men vulnerable to hepatitis C infection.
Hepatitis C prevention messages targeted at men with HIV should not just focus on condom use, say the investigators. They believe that these messages are neglecting other, potentially much more important, risk activities.
Superinfection
Researchers from the US have reported another case of HIV superinfection.
Superinfection, or reinfection, is when a person becomes infected with a second strain of HIV.
This case occurred in the early 1990s and was discovered when researchers studied stored blood samples. As in almost all the other 20 or so reported cases of superinfection, it is thought to have occurred within a few years of the person first becoming infected with HIV. The man reported unprotected sex with numerous men in the months before his superinfection.
The patient already had rapidly progressing HIV at the time of his superinfection, and the researchers think that this may have meant that his weakened immunity made him more vulnerable to infection with a second strain of HIV.
Although the man died approximately six years after he first became infected with HIV, the researchers don’t think that, in this case, superinfection worsened their patient’s prognosis. They point out that his HIV disease was already progressing rapidly prior to his reinfection, and they calculated that the rate of his CD4 cell decline was unaffected by superinfection.
MMR vaccination safe and effective in HIV-positive children
It is important that children with HIV receive vaccinations, but the protection they afford can be lost if a child had a weak immune system.
Thai doctors therefore looked at the effectiveness of MMR vaccination in HIV-positive children taking anti-HIV treatment who had a good immune system. Many of these children had previously received the MMR vaccine, but none had protective antibodies against measles when they were revaccinated.
The researchers found that six months after MMR vaccination, 80% had protective antibodies against measles, 61% against mumps and 94% against rubella.
The only side-effect reported was bruising or pain at the vaccination site that lasted between one and three days.