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4 drugs or 3? Confused.
Sep 6, 2004

This is in reference to your answer on Sept 5, "decline in cd4 with videx". You said "a 4 drug regimen does no better than a traditional 3 drug regimen". Ok.. I'll bite; My doc (and you also suggested) over a year ago that I add videx ec to my 3 drugs (viramune, epivir, viread) because my VL blipped around under 500 (once going up to 550). My VL did go undetectable one month after adding the videx ec and my cd4's have increased a little (around 300 now from 260). I have no real drug resistance.. only a "possible" resistance to epivir. So... what do you think? Drop the Videx EC and just live with the low VL's (under 500)... or stay with the 4 drugs. ?? Wow.. I'm getting really confused. One more thing.. can you site the data that shows 3 drugs is just as effective as 4? I've always been concerned using Videx EC.... with viread.. should I be? Thank you!

Response from Dr. Pierone

Hello again. Yes, for treatment nave patients with no resistance a 4 drug regimen does no better than a 3 drug regimen. Here is an abstract from the recent International AIDS Conference that speaks to this issue:

A meta-analysis of the virologic efficacy of regimens containing four versus three active antiretroviral agents as initial therapy for HIV-1 infection G J Moyle1, W Sawyer2, A Hill3 1Chelsea and Westminster Hospital, London, United Kingdom; 2PharmaNet, High Wycombe, United Kingdom; 3Roche Products, Welwyn Garden City, United Kingdom

Introduction: A combination of 3 antiretroviral agents is the current standard of care for initial HIV therapy, but sub-optimal responses are seen in clinical trials and cohorts. Additional antiretrovirals may increase the likelihood or durability of a response. Non-randomised studies of 3 class regimens consisting of 4 or 5 agents have shown more rapid initial declines in HIV RNA, compared to two class triple therapy.

Methodology: Literature was searched using Cochrane methodology and investigators contacted as needed. Studies included were in treatment nave adults, randomized and comparative of a regimens of 3 vs 4 or more antiretrovirals and had available 48-52-week HIV RNA intent to treat (ITT) outcomes with a cut off of 50cps/ml. Where not available, 400 copy data (2 trials) and 24 week data (1 trial) was used. The method of DeSimonian and Laird was used for meta-analysis of the HIV RNA response data.

Results: Nine studies met the inclusion criteria (SPICE, the Danish PI study, NZTA4002 ACTG 384, ACTG 388, CHARM, 2NN, C&W Quad study, Frankfurt Quad study). 1180 patients received triple therapy and 1187 patients quadruple therapy. Baseline demographics included a wide range of CD4 counts (range of means 22-365/mm3) and viral loads (range of means 4.8-5.4 log10). All individual studies had well matched for baseline characteristics. A test for heterogeneity indicated considerable variation between studies in the proportion of patients with less than 50cps/ml after 48 weeks of treatment. The estimated overall mean difference (quadruple-triple) in percent with HIV RNA response was -2.39% (95% CI -8.2%, 3.4%) (p=0.42). Most trials showed trends for higher rates of Grade 3 or 4 adverse events for 4 drug HAART.

Conclusion: This meta-analysis of randomised controlled studies indicates that 4 drugs do not improve ITT virologic efficacy outcomes relative to standard 3 drug regimens. 4 drug regimens cannot be recommended as initial therapy for HIV-1 infection.

Your situation is different because persistent viral replication on a triple regimen means that resistance is present. In your case, the M184V mutation that confers resistance to Epivir would be typical (although it may not be possible to confirm this with a viral load below 1000 because of limitations in resistance testing).

Adding a 4th drug to a failing regimen is known as intensification. It often works for early failure, especially when there is a very low level viral load. There are not many intensification studies in the literature, but the idea does make sense.

The combination of Videx and Viread is ok (but not as part of a triple nuke only regimen) and the data showing tendency for CD4 count declines is preliminary. In your case, I would continue the 4 drug regimen, but do make sure that the dose adjustment for co-administration with Viread has been done properly. This should be Videx EC 250mg for weight above 60kg (132 lbs) and 200mg Videx EC for weight less than 60kg.

Thanks for posting and good luck.

undetected viral loads when first infected
SN 1212 in development

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