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Feb 6, 2005

Hi Ben.

As a guy living in the UK, if starting treatment with a CD4 count of less than 200, would you recommend starting with either a Combivir/Sustiva or Truvada/Sustiva combination?

Combivir/Sustiva seems to be the most highly recommended of all the first line therapies I have researched.

Or due to the lower CD4 count, would you initialise 2 x NRTIS with a Protease Inhibitor, e.g. Kaletra?

By the way, congratulations on a very informative and excellently run web site.

There aren't too many like it in the UK!


Response from Dr. Young

Dear FG-

Thank you for your post-- it's nice to hear from patients in the UK. While our site is based primarily in the US, clearly our comments (and language) apply readily in the UK as well.

We're all the benefactors of having some really good choices in the selection of first-line HIV treatments. As you point out, Combivir (AZT/3TC) with efavirenz (Sustiva, Stocrin) is one of the most highly recommended treatment combinations. It has very long-term data, even longer-term clinical experience (especially with AZT and 3TC), excellent durability and in general, excellent tolerability. Combivir/Sustiva remains at the top of the list on the treatment guidelines in both the US and the UK.

Truvada (tenofovir/FTC) is the challenger to the throne-- two relatively newer medication that are probably better tolerated in the short term; in the ongoing Gilead 934 clinical trial, Truvada seems to perform better from a tolerability standpoint than Combivir. The major difference between the two drugs in this study is the side effect profile-- slightly more patients discontinued Combivir because of nausea and anemia than those who discontinued Truvada. In a recent press release, Gilead announced their preliminary 48 week analyses-- confirming the earlier differences and showing a small increase in CD4 cell rise too. Tenofovir has been widely prescribed around the world and has a lot of clinical trials data in combination with 3TC; it's important to recognize that Truvada is a newer pairing of medications (particularly FTC) and there are a paucity of clinical studies with the combination (one with Sustiva, one with Kaletra)-- both studies are favorable and demonstrate excellent performance. By the way, from what I understand, Truvada is not yet approved for use in the UK (though will be in the near future).

Another option that has received attention in the US (and now approved in the UK) is the nuke combination of abacavir+3TC (known in our country as Epzicom and in yours as Kivexa). This combination has also been studied with Sustiva (and boosted PIs); demonstrating very good results as well. We've been using this combo for quite a while with excellent clinical responses.

Since you've raised the point, we've been initiating an increasing number of patients on ritonavir-boosted protease inhibitor therapy. The reason for the shift from non-nukes to PIs has been the recent approval of easier to take, probably better tolerated PIs, particularly fosamprenavir and atazanavir. Both are approved in the States as once-daily medications, though in the UK, the former is only approved as a twice-daily and the later approved only for treatment-experienced patients. In this arena, Kaletra is the industry standard with the greatest amount of long-term clinical data. Both Kaletra and boosted fosamprenavir have strong data that demonstrate favorable resistance patterns among patients who experience treatment failure, with much less drug resistance-- almost certainly preserving more future treatment options that after failure of non-nuke-based treatments. It's this latter point that resonates with my patients who are choosing their first treatments. Indeed, many patients who once declined treatments with Kaletra (because of pill burden or side effects) are now electing to start treatment with ritonavir-boosted fosamprenavir or atazanavir, despite the fact that neither have reached the gold-standard of the "preferred" regimens by treatment guidelines (yet).

All of the current treatment combinations appear to have really exemplary performance in patients with CD4 counts below 200; indeed, even in patients with counts below 50. The major differences (if any) appear to be the risk of developing drug resistance among the patients with the very lowest CD4 counts and highest viral loads.

I hope this helps. Thanks for posting your questions and for your kind words. Good luck, good health.

Cheers, BY

Very low platelet count
Resistance now or later

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