Welcome to HIV Weekly, a weekly email bulletin that provides people with, or affected by, HIV a concise, plain English digest of a selection of the very latest HIV news.

This digest puts the latest HIV news stories into their context to equip you with the knowledge to understand what the latest research might mean for your HIV treatment and care.

Information on the latest NAM treatment information resources and those produced by other key organisations such as the UK Coalition and THT are also included.

HIV Weekly is edited by Michael Carter, NAM's patient information and news editor.

This week’s edition is, once again, devoted to news from the Thirteen Conference on Retroviruses and Opportunistic Infections (CROI), which was held in Denver earlier this month. CROI is one of the major HIV conferences of the year and this year’s conference was particularly interesting with lots of important information presented on all aspects of HIV.

This edition of HIV weekly is divided into six main sections:

• Adherence: Ritonavir-boosted protease inhibitors may need a lower level of adherence than unboosted protease inhibitors or non-nucleoside reverse transcriptase inhibitors.
• Sexual health: The immune system’s ability to produce a certain kind of antibody might be the key to preventing superinfection with other strains of HIV; and more information on the prevalence and risk factors for the sexual transmission of hepatitis C virus.
• Side-effects: Long-term use of anti-HIV treatment doesn’t seem to have any strong association with liver disease or death because of liver-related causes.
• HIV and hepatitis: Anti-hepatitis C treatment can lead to an improvement in liver fibrosis in people who also have HIV. But it can take a long time to see results.
• Illness: Anti-HIV treatment should be started promptly in people with brain impairment caused by HIV, otherwise there’s a risk that any damage may be irreversible.
• Mother-to-child transmission: Saquinavir boosted by ritonavir is safe and effective when used with Combivir  to prevent mother-to-child transmission of HIV.
• Children: Once lipodystrophy develops in children taking anti-HIV treatment, it stays put.

Adherence

For anti-HIV treatment to work most effectively it is important to take it properly.

This means taking all the prescribed doses, at the right time, observing any food restrictions, and making sure that you don’t take any other drugs that can interact with your medication.

The term used for taking your medication properly is adherence.

Studies suggest that to have the best chance of your viral load falling to undetectable and staying there, it’s necessary to take at least 95% of all your doses. If you don’t manage such high levels of adherence, there’s a chance that HIV in your body will become resistant to some or all the drugs you are taking. There’s also a risk that you could develop resistance to anti-HIV drugs similar to the ones you are taking.

The exact risk of resistance emerging with adherence below 95% differs between classes of anti-HIV drugs. It is thought that it is easier to develop resistance due to poor adherence to the non-nucleoside reverse transcriptase inhibitor drugs - efavirenz (Sustiva) and nevirapine (Viramune) - and the ‘unboosted protease’ - inhibitors nelfinavir (Viracept) and indinavir (Crixivan) -  than the ritonavir-boosted protease inhibitors ( Kaletra , saquinavir/ritonavir, atazanavir/ritonavir, indinavir/ritonavir, and tipranavir/ritonavir).

A Canadian study presented to CROI appears to confirm this. It found that, amongst people with adherence below 95%, viral load was most likely to increase in those taking NNRTIs, followed by those taking unboosted protease inhibitors, and that people taking boosted protease inhibitors had the smallest risk of experiencing a rebound in their viral load.

The researchers think that this is because there are higher blood levels of boosted protease inhibitors and that boosted protease inhibitors stay in the blood longer than the other classes of drugs, meaning it’s less serious if a dose is missed.

However, although a difference was seen between the three groups of patients it was not ‘statistically significant.’ This means that there’s a chance that if the study were repeated, it would produce entirely different results.

It’s important to do your best to take every dose of your HIV medicine correctly. Adherence is the single most important factor in your control affecting the success of your HIV treatment. If you are having problems, then ask your doctor or another member of your healthcare team for help.

More information about taking your HIV treatment is available in the NAM information booklet, Adherence.

Sexual health

Side-effects

All medicines have unwanted side-effects, and anti-HIV drugs an cause both short term unwanted effects, such as diarrhoea and headache, and longer term problems, such as changes in body fat shape (lipodystrophy), and elevations in blood fats and sugars which can increase the risk of diabetes and heart disease.

A major study called D:A:D (Data collection on Adverse events of anti-HIV Drugs) is looking at anti-HIV drugs and their risk of side-effects. It is  very large and involves over 23,000 people taking HIV treatment around the world. Information from the study has already shown that long-term use of protease inhibitors, but not NNRTIs, is associated with an increased risk of heart disease.

Researchers from the D:A:D study have also been looking at the effect of anti-HIV drugs on the liver. The liver plays a key part in processing medicines used to treat HIV and other infections to which people with HIV are vulnerable to. However, some anti-HIV drugs can be toxic to the liver, and what’s more, many people with HIV are also infected with hepatitis B and/or hepatitis C which can cause severe liver disease.

According to results presented to CROI, the main risk factors for liver-related death and illness in people taking anti-HIV treatment are low CD4 cell count and coinfection with hepatitis B and/or hepatitis C.

In their first analysis they found no association between long-term use of anti-HIV drugs (up to seven years) and the risk of liver-related death. But when they repeated their analysis and took into account how much a person’s CD4 cell count had increased since they started HIV treatment, they did find that use of HIV treatment for over four years was associated with an increased risk of liver disease.

A total of 90% of people in the study who experienced liver disease of dying of liver-related causes had hepatitis B and/or hepatitis C. It could well be the case that HIV treatment kept them alive, only for long-term liver damage caused by infection with viral hepatitis to cause illness and death.

HIV and hepatitis

The current standard of hepatitis C treatment is pegylated interferon with ribavirin. The aim of this treatment is to eradicate hepatitis C,  as indicated by a sustained virological response (a negative hepatitis C viral load after treatment is completed) and an improvement in liver scarring, or fibrosis.

Hepatitis C treatment works less well in people who have HIV as well as hepatitis C, both in terms of the number of people who achieve a sustained virological response and experience an improvement in their fibrosis.

However, research presented to CROI showed that two and a half years after completing anti-hepatitis C treatment, people who experienced a sustained virological response to hepatitis C treatment were more likely to experience an improvement in their liver fibrosis. The research also indicated that FibroScan can be used to accurately monitor liver fibrosis without the use of a liver biopsy.

Illness

It is known that HIV can cause mental health problems and before potent HIV therapy became available it was feared that as many as 7% of HIV-positive people might develop brain impairment.

Thanks to effective anti-HIV treatment, the amount of illness and death caused by HIV has fallen dramatically in the UK and similar countries, and new cases of brain impairment caused by HIV are now rare. When they do occur, they tend to involve people who were diagnosed with HIV when they were already extremely ill, or people who had run out of HIV treatment options.

An Italian study presented to CROI found that two-thirds of people diagnosed with brain impairment still have problems after three years of anti-HIV treatment. They found that people with less severe brain impairment had the biggest improvements after starting HIV treatment.

They recommend that HIV treatment should be started as soon as brain impairment is diagnosed to avoid “potentially irreversible neurological damage.”

Mother-to-child transmission of HIV

HIV can be passed on from a mother to her baby, in the womb, during delivery, and by breastfeeding.

The risk of transmission can, however, be reduced to less than 1% by the use of anti-HIV drugs during pregnancy and delivery to lower the mother’s viral load, a caesarean or, if the mother has an undetectable viral load, an actively managed delivery, and by not breastfeeding.

Not all anti-HIV drugs can be used during pregnancy. The NNRTI efavirenz should not be used because there are fears that it can cause birth defects, and if a woman has a CD4 cell count above 250, she should not start treatment with nevirapine because of a risk of severe side-effects.

Pregnancy can alter the way the body metabolises drugs and levels of drugs in the blood.

Researchers in Dublin wanted to see if the protease inhibitor saquinavir (Invirase) boosted by ritonavir, used in combination with Combivir (AZT zidovudine, Retrovir), and 3TC (lamivudine, Epivir), was as safe and effective as the normal recommended treatment, nelfinavir (Viracept) and Combivir. Treatment was provided for at least six weeks, starting in the final three months of pregnancy.

A total of 88% of the women who took saquinavir/ritonavir had an undetectable viral load by week 36 of pregnancy compared to only 56% of women taking nelfinavir. One woman taking saquinavir/ritonavir had a switch to nelfinavir because of vomiting

No cases of mother-to-child transmission were seen in the women who took saquinavir/ritonavir. One woman who took nelfinavir passed on HIV to her baby. This happened even though her viral load was undetectable at the time of labour. However, her waters broke 24 hours before delivery, a recognised risk factor for transmission.

Adherence problems were reported by six women who took nelfinavir, but all had an undetectable viral load by the time of delivery. No women who took saquinavir reported adherence problems.

Women taking saquinavir had larger concentrations of the drug to fight HIV in their blood than women who took nelfinavir had in theirs.

The researchers also found that short-term use of saquinavir/ritonavir did not lead to any resistance developing.

Children

Anti-HIV treatment can mean a longer, healthier life for HIV-positive children. But, as with adults, anti-HIV treatment can cause side-effects in children, and one of the most concerning is lipodystrophy.

An Italian study presented to CROI showed that once lipodystrophy developed in children taking anti-HIV drugs it stayed put. Researchers looked at the body shape of 55 children with an average age of 14 in 2003 and again in 2004.

They found that for twelve children with fat loss and eight with fat gain around the internal organs there was no improvement or deterioration in their condition.

A further 28 children had both fat loss and fat gain. In 13 of these children, their condition worsened. An improvement was noticed in seven children.

A total of 23 children had high cholesterol at the start of the study. This improved in 14 children, but five new children experienced an elevation in their cholesterol.

In a separate study, doctors in Milan found that children who lost fat whilst taking d4T (stavudine, Zerit) and a protease inhibitor still had significantly less fat than age-matched HIV-negative children two years after switching to treatment with no association with fat loss abacavir (Ziagen) or tenofovir (Viread) and efavirenz (Sustiva).