Dear Dr Daar, I'm seeking an extra opinion on what may be the best treatment options for me. I realise that there is a lot of information to digest and that you are very busy. So I greatly appreciate your time considering this. BACKGOUND I was diagnosed with HIV in 1985. Since circa 1990 I have been on a wide range of treatment regimes. CURRENT RESULTS After 12 years of undetectable viral loads my viral load is now at 8,800 and had spiked to 70 000. My cd4 count is down to 124 from over 500 a year ago. RESISTANCE PATTERNS Resistance tests have shown my strain of virus is resistant to ALL reverse transcriptase inhibitors ( most highly resistant). The good news is that the virus is suseptible to ALL protease inhibitors. On the flip side Ritonovir gives me uncontrollable diarrhea. POSSIBLE TREATMENT REGIME My Dr has suggested a regime that includes Kaletra, Atazanavir, 3TC and an integrase inhibitor Raltegravir, if I can gain access to it but doesn't want to start me on the PI's until I can be guaranteed access to Raltegravir (not licensed yet in Australia). TREATMENT PREFERENCES in order of importance to me are efficacy, manageable or negligible acute side effects, dosing convenience (prefer not to have to take some with food and others without food). Of no concern to me is number of dosing times and number of pills.

Many thanks Harley

Hi Harley, Thank you for the posting. As you know the decision you are about to make is a very important one. It is best informed by details regarding your treatment history, past resistance testint and the specific results of your current resistance test. Expert providers also need to interpret the resistance data in the context of what medications you were on at the time the test was performed. The reason for this is that when you are off select drugs for some time resistance to those drugs that was previously present may no longer be detectable. Since I do not have all of this information about your case I must keep my comments relatively general and leave it to you and your provider to make the big decisions.

Assuming you were on protease inhibitor, and taking it at the time the last resistance test was performed then it is good news that you have no resistance to this class of drugs. I will assume based upon your posting that you probably have been on NNRTIs in the past, such as efavirenz, and it is felt that you are resistant to these drugs. The tolerability to ritonavir is a big issue and I would need more information about this, such as whether it is controlled with antidiarrheals and tolerable. In addition, whether it is true on all protease inhibiors with RTV. Since your provider is suggesting Kaletra which includes ritonavir in the drug I suspect that this side effect is tolerable and RTV-boosted PIs remain an option. If not, you would need to consider not using PIs or using ones that may not need boosting in people without protease resistance, such fosamprenavir or atazanavir.

The utility of using two fully doses PI together, such as Kaletra and atazanavir is complicated since there are important drug inteactions and little data showing that this strategy improves outcomes. Finally, what to use with a PI if you are able to take one. I would agree with your provider that you will likely need at least one if two other active drugs to combine with the PI(s). Assuming you are thought to have resistance to approved NNRTIs then possible options would be raltegravir, enfuvirtide (T-20), maraviroc (if you only have detectable R5 virus on a tropism test) and possibly the new NNRTI etravirine if you have access to it through expanded access programs and your drug resistance test suggests that you are likely to respond. Whether you need to add one or two fully active drugs to the PI is not completely known and you would need to discuss this further with your provider.

Sorry for the long answer but it is a complicated and very important question. I suspect you will do very well by combining a PI with some of the other drugs with novel targets. Best, Eric