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, dominated by news from the Thirteen Conference on Retroviruses and Opportunistic Infections (CROI), which was held in Denver in early February. 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 five main sections.

• Treatment breaks: Taking a treatment interruption guided by CD4 cell count may not involve a risk of resistance to anti-HIV drugs. Could this be because a boosted protease inhibitor was being taken by most people in the study?
• Tipranavir: After a year, tipranavir is still out-performing other boosted protease inhibitors in highly treatment-experienced people and there’s more evidence that using it with the fusion inhibitor T-20 produces good results. The dose of tipranavir for children is identified.
• HIV treatment: Only patients who start anti-HIV treatment with a CD4 cell count above 350 have a realistic chance of experiencing an increase in their CD4 cell count to normal levels, a finding which could have implications for decisions about the best time to start HIV treatment. Children need to start HIV treatment before they experience extensive immune damage to have the best chance of experiencing immune recovery.
• Lipodystrophy: There’s evidence that traditional risk factors such as smoking and high blood fats are behind the increased risk of heart disease seen in some people taking HIV treatment.
• Illness: Potent anti-HIV treatment and chemotherapy for non-Hodgkin’s lymphoma can be used together safely and successfully. A study finds that even when anti-HIV treatment isn’t working well, it still reduces the risk of developing an AIDS-defining illness.

Treatment breaks

One of the biggest HIV news stories so far this year was the early termination of the SMART treatment interruption study after it was found that people who took a break from treatment were much more likely to become ill. The researchers coordinating the study concluded that CD4 guided treatment interruptions were unsafe after it was found that people who stopped taking treatment when their CD4 cell count reached 350 were not only more likely to experience AIDS-defining illnesses but other serious illnesses as well.

The SMART study is not the only examination of the safety and effectiveness of taking a treatment break on the basis of CD4 cell count. Results from another such study, called the Staccato trial, were also presented to CROI. In contrast to SMART, this trial had relatively encouraging results and found that 92% of people who took a break from treatment when they had a viral load above 500 copies/ml did not develop resistance to their anti-HIV drugs. Taking a treatment break with a detectable viral load is a recognised risk factor for the emergence of resistance.

Doctors from the Staccato study think that the reason so few people developed resistance in their study was because 80% were taking the saquinavir (Invirase)boosted by ritonavir. This drug, like all the ritonavir boosted protease inhibitors is very powerful and it is difficult for HIV to become resistant to it.

You can read an analysis of the future of treatment interruptions here.

New drug tipranavir

Tipranavir (Aptivus) is a ritonavir-boosted protease inhibitor which was recently licensed for use by people who have taken a lot of anti-HIV drugs before and have very limited treatment options.

There were a number of studies presented to CROI which provided more information on the potency of tipranavir and how best to use the drug.

Tipranavir for a year

Results from two studies showed that heavily treatment-experienced people taking tipranavir were much more likely to see a significant fall in their viral load a year after starting treatment with the drug than people with similar characteristics who took an alternative boosted protease inhibitor. The studies also found that people taking tipranavir were 34% less likely to experience treatment failure than those taking alternative treatments,  and that the best response to tipranavir was seen in people who started taking the drug when their viral load was below 10,000 copies/ml and their CD4 cell count 200 or higher.

Tipranavir and T-20

The fusion inhibitor T-20 (enfuvirtide, Fuzeon) is often used in combination with tipranavir, and an Italian research presented to the conference showed that tipranavir concentrations in the blood were higher in people who took T-20 and that tipranavir remained in the blood of people who also took T-20 for longer.

Tipranavir for children

Research presented to the conference showed that the dose of tipranavir for children is 290/115mg

Anti-HIV treatment

The aim of treatment with a powerful combination of anti-HIV drugs for people who have never taken anti-HIV therapy before is to suppress viral load to undetectable levels. Suppression of HIV allows the number of the immune system’s key CD4 cells to increase.

The recovery of CD4 cell count during anti-HIV treatment was the subject of several presentations to CROI. The findings of one of these studies could have implications for decisions about the best time to start anti-HIV treatment.

CD4 cell recovery

An American study found that only people who started HIV treatment when their CD4 cell count was above 350 (higher than the current 200 – 250 trigger for treatment) had a good chance of seeing their CD4 cell count increase to normal levels.

This presentation and a large Dutch study also showed that the CD4 cell count continued to increase for many patients up to seven years after starting HIV treatment.

Immune therapy

A small British study was also presented to the conference showing that the use of daily injections of recombinant human growth hormone increased the number of immune cells specifically created to fight HIV when used along with traditional anti-HIV treatment. The researchers think that this strategy may be a way of “kick-starting” a strong immune response to HIV treatment.

CD4 cell recovery in children

Anti-HIV treatment can mean a longer and healthier life for HIV-positive children. However, less is know about the effectiveness of HIV treatment in children.

It is recommended that HIV treatment should be started when a child has experienced the same extent of immune damage as an adult. However, CD4 cell counts need to be interpreted differently in children under six, as they are naturally higher than those seen in adults. In a baby aged under twelve months, a CD4 cell count of 700 is the equivalent of an adult count of  200. For a one-to-five year old, a count of 500 is equivalent to an adult count of 200. Rather than looking at CD4 cell counts, doctors sometimes make their decision on when to start HIV treatment in children by looking at CD4 cell percentage.

According to a recently published Spanish study, children who start HIV treatment with a CD4 cell percentage below 5% failed to reach the normal 25% level after six years of anti-HIV treatment. The researchers found that children who started HIV treatment with a CD4 cell percentage between 5% -15% were much more likely to see their CD4 cell percentage return to normal levels with long-term HIV treatment.

This finding could have implications for when HIV treatment is started in children as the Spanish doctors conclude, “these data argue in favour of not delaying the initiation of [HIV therapy] in young children.”

Lipodystrophy

Anti-HIV drugs have been associated with changes in body fat shape and increases in blood fats, which can increase the long-term risk of heart disease. The name given to these side-effects is lipodystrophy.

Results from a very large study presented to CROI showed that protease inhibitors that involve the biggest risk of heart disease.

Several other studies looking at the risk of heart disease in people taking anti-HIV drugs were also presented to CROI.

Heart disease risk and risk reduction

A study conducted in California found that HIV-positive men were much more likely than HIV-negative men to have a heart disease. The researchers also found that HIV-positive men who took a protease inhibitor had an increased risk of heart disease compared to men who did not take this class of anti-HIV drug. The risk associated with protease inhibitor use was not as significant as that seen in the D:A:D study and the researchers think that this could be because of initiatives to reduce heart attack risk in their study, such as stopping smoking, the use of drugs to reduce the amount of fat in the blood, and the use of the newer protease inhibitor atazanavir (Reyataz) which is less likely to cause lipid increases.

Traditional risk factors

Another American study, however, found that switching to atazanavir of a non-nucleoside reverse transcriptase inhibitor did not significantly reduce the risk of heart disease.

Researchers from the HIV Outpatients Study (HOPS) found that heart disease was associated with the traditional risk factors of age over 40, diabetes, increased levels of blood fats and high blood pressure. The use of drugs to lower blood fats reduced the risk of heart disease.

Genes and lipodystrophy

Some very preliminary research was presented at CROI looking at how a person’s genes influence their risk of developing lipodystrophy. One study found a link between a gene associated with resistance to multiple anti-HIV drugs and fat accumulation and increased cholesterol.

Looking at how a person’s genes might affect their health or response to treatment is likely to become increasingly important to HIV medicine in the coming years. A test is already being used to check if people have a gene which can cause an allergic reaction to the anti-HIV drug abacavir (Ziagen).

Illness

Lymphoma treatment

Non-Hodgkin’s lymphoma is an AIDS-defining cancer. The number of people dying because of HIV has fallen dramatically since the introduction of effective anti-HIV treatment. However, because the number of deaths caused by other HIV-related infections and cancers has fallen so markedly in recent years, the proportion of deaths caused by non-Hodgkin’s lymphoma has increased.

Some doctors are concerned that the aggressive treatment of non-Hodgkin’s lymphoma with anti-HIV drugs and chemotherapy at the same time could lead to drug interactions. Because of this, some doctors either delay starting HIV treatment or interrupt HIV treatment so they can use chemotherapy.

German researchers have shown, however, that anti-HIV therapy and chemotherapy for non-Hodgkin’s lymphoma can be effective and safe when used together. The use of both therapies together lead to good rates of remission and survival. The best results were seen in people who were treated for HIV and lymphoma when they still had a relatively strong immune system.

Anti-HIV treatment and AIDS

Even when a person is not responding well to anti-HIV treatment, their risk of becoming ill with an AIDS-defining illness is still reduced, American researchers have found.

Doctors compared the number of AIDS-defining illness experienced by people with the worst response to potent anti-HIV treatment - a CD4 cell count below 50 and a viral load above 100,000 - with the number of AIDS-defining illness experienced by people with a similar degree of immune damage who had taken single or dual nucleoside analogue treatment between 1990 and 1995.

They found that people taking potent HIV treatment had significantly fewer AIDS-defining illness. This was also the case when they looked compared patients who have a CD4 cell count between 100 – 200 and a viral load above 100,000.

The researchers offer two explanations for their findings. Firstly, people with a poor response to potent HIV treatment could have more resistant HIV that is less aggressive and likely to cause disease than wild-type HIV. An alternative explanation could be that the immune systems of people treated with potent HIV therapy may have more cells able to recognise and combat disease-causing organisms.