Hello, I'm a 34 year old female and my husband and I were diagnosed with HIV some years ago. Now my cd4 has been dropping to 310, VL 160.000, so I have no choice but to start therapy. I will do so, but I have a couple of considerations and I wonder which combo would fit them best: First of all it should best fit with our wish to have a child... Secondly, I want to be able to have a treatment interuption if the medical situation would allow that (it seems to me I would live longer with treatment interuptions than without). I'm therefor wondering if I should start on Nevirapine and Combivir, since 3TC stays in the body for a long time, and I might be at risk developping resistance to 3TC? Thirtly I have suffered quite badly from neuropathy in the past. The worst part of this has passed away since I started taking vitamine B12-shots and lots of other supplements I read about on this site (thank you for that!). Now I'm worried that - because I already have had neuropathy without medicines -it's prone to come back easily once I start with a triple. Beside all this there's one more thing to consider: almost nobody knows that we're HIV-positive, and although this has been very heavy, it certainly has had many benefits too, so we plan to keep it that way. Therefor I'm afraid of any combo which gives a greater chance of developping lipodystropy. I really don't want that. And lastly I don't want my taking medicines now, interfere with my chance of using T-20 or a therapeutic vaccine in the future. So.... I realize these are a lot of questions to answer, but I sure hope somebody can answer them for me. Thanks a lot in advance!

Well, yes, these are a handful of criteria to consider - but thankfully we have enough meds to see what is left after considering all of these. One concern however is that some of your criteria might take us in conflicting directions... and for others, we just aren't sure what the answer should be yet.

For staters - your viral load. As it is over 100,000 there are some concerns that some combinations will not be quite potent enough - at least some of our 3-drug combos have been less successful for those with this degree of viral load. The few that have stood out as particularly reliable at even high viral loads have been combinations based on two "nukes" and Sustiva, as well as two nukes and Kaletra, and potentially other "boosted" PIs. The data on nelfinavir, a nonboosted PI - has been variable at higher viral loads, and the data on nevirapine is somewhat more controversial on this issue - as some but not all studies suggest it is acceptable at higher viral loads. Triple "nuke" combinations (Trizivir) is also generally considered not adequate for this higher viral load.

Now, Sustiva is among the few antivirals that we try to avoid during pregnancy based on some animal data. That now leaves the "boosted" PIs and perhaps nevirapine for three drug combos.

As for neuropathy, that would lead us in general to avoid the three "d" nucleosides that have this side effect noted -this includes ddI, ddC and d4T.

So - as you note - Combivir (AZT plus 3TC) plus nevirapine is a combination to consider. The other 2 NRTI combinations to consider as alternatives include 3TC plus abacavir, and with the arrival of tenofovir as the new kid in town, related to these - it too could be used as one of the two NRTIs once it is FDA approved.

Now - as to which combinations lead to lipodystrophy. The short answer is that we are not entirely sure. The longer answer is that, in general, single class regimens (triple nuke or dual PI) have had less lipodystrophy reported than those that have added both nukes and PIs together. And so far no one finds any role of the nonnuke in accelerating this problem. So that still leaves you with 2 NRTI plus nevirapine, or, a less common choice using dual PIs plus a nonnuke. Tenofovir is for now considered potentially a drug with a lower likelihood of lipodystrophy, but it is too soon to know how that prediction will play out.

Now - one way around the concern for nevirapine at higher viral loads would be to at least initially use a fourth agent - for example AZT/3TC/Nevirapine and add abacavir as the fourth drug. The problem here is both nevirapine and abacavir can have a similar rash/fever in the first few weeks for a few, and this has led to some concern for the use of these two when started together. Here again, tenofovir when available could be the fourth drug instead, when it becomes available - so for example, Combivir/nevirapine/tenofovir.

But, finally, meds on which to do treatment interruptions. While it is reasonable to have hope, it should be noted that we really don't know if treatment interruptions would help you live longer - it may, but it may result in more problems from, for example, resistance. And thus, it could lead to the paradox of shortening the time that these meds work for you. This resistance is of particular concern when doing STIs for more than a week, and using meds that stay in the body a longer time - which is true for nevirapine for example, and some concern albeit less for 3TC. But as you note, some have voiced at least theoretical concerns about using 3TC in STIs. The news so far is pretty reassuring from the first 100 pts or so who have used it - but... Now, while tenofovir also lasts a long time in the body - resistance has been slow to develop to it - so it could be a choice during STIs.

So if we are very conservative - that leads to even fewer combinations - if we exclude both the nonnukes and 3TC - it leaves only dual PI based combinations. This would include the most studied of all --ritonavir/saquinavir, but even this wasn't adequate at higher viral loads - so we'd need more "modern" versions such as Kaletra/saquinavir - or other variations on the dual boosted PI theme. This may be enough for a higher viral load - or you could add tenofovir for added potency again when it becomes available. The challenge here is dose - as we are all in search of data to guide the "best" dose of dual boosted PIs - sites are working on this now, but we don't have it yet, just informed starting points.

Now the easy part - whichever of these you do -- none of them would interfere with doing vaccination type approaches, or using T20 in the future.

So as you can see there are balances to be made as there does not appear to be a perfect combo that fits all of your needs. The answer above is meant to be a reasonable review of options without a conclusion - since I don't know we have a "best" answer. But there are some that get close.

And - one more point. IF you are able to get your viral load to <50 on whatever you start on - and continue taking meds daily as needed - then you are very unlikely to have resistance develop. If that happens - you can then maintain the sensitivity of your HIV to ALL meds. Which means you can do substitutions as needed - starting on one combo now, and switching later as your circumstances and needs change. For example, you could do Combivir/Sustiva now, and when pregnancy is the plan, you can substitute another med for the Sustiva. And if there is concern for lipodystrophy, make switches to meds that hopefully decrease that risk. And so on... That type of thinking may make this first choice much easier to plan for...

Good luck. Hope that helps.