Starting anti-HIV treatment should be discussed with all patients with a CD4 cell count of around 350 cells/mm3, and therapy should be started as soon as the patient is ready, according to Prof Brian Gazzard, who was outlining the contents of new draft British HIV Association (BHIVA) treatment guidelines at a NAM information forum in London on March 31st.
The draft guidelines also recommend efavirenz (Sustiva) with Truvada (tenofovir and FTC) as the preferred first-line therapy. The draft update to British treatment guidelines is expected to be posted for comment on BHIVA’s website – www.bhiva.org - in the next day or so.
When to start treatment
In the last year updated HIV treatment guidelines issued in the US and Europe have included a recommendation that anti-HIV treatment should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3. Results from the SMART treatment interruption study showed that untreated patients with a CD4 cell count below 350 cells/mm3 had an increased risk of not only HIV-related illness, but some other serious conditions, including heart, kidney and liver disease, as well as some cancers.
It has long been anticipated that the updated British guidelines would also include a recommendation to start treatment at a CD4 cell count of 350 cells/mm3, not least because Prof Brian Gazzard, chair of the guidelines committee, co-authored an article in the British Medical Journal outlining the potential benefits of earlier anti-HIV therapy.
Although also recommending treatment at around 350 cells/mm3, Prof Gazzard emphasised that the draft British guidelines reiterate the importance of starting therapy before a patient’s CD4 cell count has fallen to below 200 cells/mm3 - the threshold for the initiation of treatment in the last guidelines. The British recommendation to start treatment at a CD4 cell count of 350 cells/mm3 is somewhat softer than the US and European guidelines, stating, “our recommendation is that the initiation of therapy should be discussed with all patients with a confirmed CD4 cell count
Treatment at this time is particularly encouraged for patients with any of the following characteristics: HIV-related symptoms; a high viral load; a rapidly falling CD4 cell count; hepatitis B or C coinfection; older age; patients, particularly of African ethnicity with a risk of kidney disease; or patients with a significant risk of cardiovascular disease.
Some research has suggested that there may be some benefits to starting treatment when a patient’s CD4 cell count is as high as 500 cells/mm3. But Prof Gazzard stated that the draft guidelines say that any reduction in the risk of death or disease progression will be low, and that should a patient wish to start treatment at a higher CD4 cell count they should be enrolled on a “when to start” study.
What to start with – efavirenz
Efavirenz (Sustiva) should be considered for all patients starting anti-HIV treatment for the first time, said Prof Gazzard. The non-nucleoside reverse transcriptase inhibitor (NNRTI) is recommended in the draft guidelines over a boosted protease inhibitor because of its efficacy, convenience and relative lack of toxicity.
However, a ritonavir-boosted protease inhibitor is an alternative for patients who were infected with HIV that is resistant to NRTIs or NNRTIs, women who wish to become pregnant, or patients with psychiatric problems. Should first-line therapy include a protease inhibitor, the options are lopinavir/ritonavir (Kaletra), boosted fosamprenavir (Telzir), boosted saquinavir (Invirase), boosted atazanavir (Reyataz - not currently licensed for treatment-naïve patients), or boosted darunavir (Prezista - not currently licensed for treatment-naïve patients).
Nevirapine (Viramune), the other licensed NNRTI, is mentioned as an alternative treatment for pregnant women, women wishing to become pregnant, or patients with mental health problems. Women with a CD4 cell count above 250 cells/mm3 and men with a CD4 cell count above 400 cells/mm3 should not start treatment with nevirapine because of a risk of serious liver-related side-effects, cautioned Prof Gazzard.
What to start with - Truvada
The recommended first-line NRTI backbone is Truvada (tenofovir and FTC) rather than Kivexa (abacavir and 3TC).
Prof Gazzard explained the reasons for this, referring to a recent study showing Truvada’s superior virological efficacy in patients with a baseline viral load above 100,000 copies/ml. During the preparation of the guidelines, results from the D:A:D study appeared to show an increased risk of heart attack in abacavir-treated individuals, particularly in patients with pre-existing risk factors for cardiovascular disease. These results are incomplete, said Prof Gazzard, and did not include an analysis of tenofovir or FTC. Nevertheless, the draft guidelines recommend that the results should “caution” against the choice of Kivexa in patients with risk factors for heart disease.
AZT has been associated with fat loss, and because of this Combivir ceased to be an option for first-line antiretroviral therapy in the 2006 guidelines. But Prof Gazzard believes that it could be an option for women who wish to become pregnant.
New drugs
Etravirine, the currently unlicensed NNRTI, was mentioned by Prof Gazzard as being a potentially attractive for patients starting anti-HIV therapy, as well as those with resistance to existing NNRTIs.
Use of maraviroc (Celsentri) will remain confined to treatment-experienced patients with CCR5-tropic HIV. He noted, however, that it currently takes six weeks for the results of tropism tests to be processed.
Raltegravir (Isentress) was also mentioned as being an important treatment option for treatment-experienced patients, and Prof Gazzard regarded results from clinical trials showing an association between treatment with the drug and an increased risk of cancer as a “red herring.”