HIV Weekly - September 12th 2007

It is recommended that people starting anti-HIV treatment for the first time should do so with a combination that includes two NRTI drugs and an NNRTI (efavirenz, Sustiva, or nevirapine, Viramune). An alternative is to replace the NNRTI with a protease inhibitor that has its potency boosted by a small dose of ritonavir.

Some doctors and patients think that an NNRTI is preferable because treatment with this class of drug tends to involve fewer pills and side-effects. They also argue that taking an NNRTI first saves a boosted protease inhibitor as a treatment option for later.

It is known that combinations that include either NNRTIs or boosted protease inhibitors are equally powerful and effective.

A new study suggests that there may be some advantages to starting treatment with a boosted protease inhibitor.

HIV can become resistant to the drugs used for its treatment. Developing resistance to one anti-HIV drug can mean that you also develop resistance to other, similar drugs. This is particularly the case with NNRTIs.

Researchers in Switzerland found that equal  numbers of patients taking NNRTIs or a boosted protease inhibitor experienced a rebound in their viral load to detectable levels. But people who taking an NNRTI whose treatment failed were much more likely to develop drug-resistant HIV. Not only was this HIV resistant to NNRTIs, it also often developed resistance to the key NRTI drugs 3TC (lamivudine, Epivir) and FTC (emtricitabine, Emtriva) as well.

Because of this risk of multi-drug resistant HIV, the Swiss researchers recommend that “physicians should critically asses a patient’s ability to adhere to NNRTI-based regimens and to cope with the potentially toxic effects, such as adverse effects on the central nervous system. If problems are expected, starting or changing to a protease inhibitor boosted by ritonavir represents a safer choice”.

The main reason why people develop resistance to anti-HIV drugs is because they don’t take their treatment properly. Anti-HIV drugs have to be taken very rigorously to work properly. The technical term used for taking your HIV treatment correctly is adherence.

An American study has found that using pillboxes, which contain separate compartments for each dose of pills for each day, improves adherence to treatment.

Some experts believe that the benefits of pillboxes are such that they should be issued as standard to people taking anti-HIV treatment.

Many HIV clinics already give pillboxes to their patients, so if you think that you might find one useful ask if they are available.

Like all anti-HIV drugs, the NNRTI nevirapine can cause side-effects. The most serious side-effects caused by this drug are rash and potentially fatal liver problems. Men who have a CD4 cell count above 400 and women whose CD4 cell count is above 250 have the greatest risk of experiencing such side-effects and should not start treatment with nevirapine.

HIV can be a lot harder to treat in people who have taken a lot of anti-HIV drugs and have drug resistant virus.

But thanks to the development of new, more powerful drugs, like the boosted protease inhibitors tipranavir (Aptivus) and darunavir (Prezista), and the use of resistance tests to select the combination of drugs with the best chance of success, there is now a good chance that heavily treatment-experienced people will be able to get and sustain an undetectable viral load.

These new protease inhibitors often produce the best results when they are combined with the fusion inhibitor T-20 (enfuvirtide, Fuzeon).

There was recently a case report of a person taking boosted tipranavir with T-20 having very high levels of tipranavir in his blood, this leading to liver problems. Importantly, the man was also infected with hepatitis B virus. This patient’s doctors recommended that the doses of tipranavir or ritonavir should be adjusted to prevent liver problems happening.

Because of this case report  the researchers who conducted the trial to determine the safety and effectiveness of tipranavir looked at their results again to see if taking boosted tipranavir with T-20 did actually increase levels of tipranavir and lead to liver problems.

They found that T-20 did indeed boost blood levels of tipranavir and other protease inhibitors as well. However, they found that people taking T-20 with tipranavir actually were less likely to develop liver problems than those whose treatment didn’t include the fusion inhibitor. 

The researchers conclude “on the basis of these results from a large clinical trial, [we] discourage any recommendations to alter ritonavir or tipranavir dosing in patients receiving tipranavir/ritonavir plus T-20 as this may result in clinically significant underexposure to tipranavir and loss of antiretroviral efficacy”.

In June the protease inhibitor nelfinavir (Viracept) was recalled in Europe and most other countries (with the exception of Canada, Japan and the USA) after it was found that an excess amount of a substance used in the drug’s manufacture than can cause cancer in very large doses, had contaminated certain batches.

Although the USA was not affected by the recall, drug regulatory authorities there have issued guidance about the use of nelfinavir in pregnant women and children. They recommend that pregnant women should not take nelfinavir if they have other options available and that children should not start treatment with nelfinavir. Children who are already taking nelfinavir can, however, remain on the drug.

HIV-related illness has become much rarer thanks to effective anti-HIV treatment and dementia caused by HIV is now quite rare.

But cases are still seen, and a new study has found that in HIV-positive people with low CD4 cell counts (below 200), a low platelet count in the blood predicts who has a risk of developing dementia.

A separate study found that mild cognitive impairment is common in people with HIV, even if they are taking anti-HIV treatment. The study found that almost 40% of people had some form of brain impairment, such as slow memory, six months after starting anti-HIV treatment. The condition improved in 44% of these people.

The lower a person’s CD4 cell count before they started anti-HIV treatment, the greater their risk of cognitive impairment. Older age was also a risk factor for brain impairment.

Not all anti-HIV drugs can get into the brain and the researchers think that is why so many people had problems such as mild memory loss despite taking anti-HIV drugs.

Thanks to the success of anti-HIV treatment many people with HIV can look forward to living a long and healthy life. Because of this, some are considering parenthood.

Unprotected sex can involve a risk of HIV transmission in couples where one of the partners is HIV-negative.

But doctors have developed a technique called sperm washing that removes HIV from sperm that is then used for artificial insemination.

A new Europe-wide study has shown that sperm washing is very safe. Not a single case of HIV transmission occurred in over 1000 couples. The researchers concluded that the risk of HIV transmission from sperm washing was “zero.”

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