By: Dr. Geoffrey Modest
NIH just published the 2015 updated HIV guidelines. For the 11-page summary of recommendations (see here). For full guidelines (all 288 pages) see here.
Brief summary of significant changes below:
–drug resistance testing: no real changes. But just as a reminder, in the setting of virologic failure, the genotype is more accurate if done within 4 weeks of discontinuing prior therapy, before there is a rebound of the suppressed virus which potentially obscures the genotype of the resistant virus. (But the genotype should be done anyway, even if later than 4 weeks, since you might get useful information). Also do prior to starting meds. Add phenotype if patient likely has complex drug-resistant mutations
–when to start therapy? (also not a change): evidence strongest for CD4 <500, but importance of “treatment as prevention” as a means to decrease viral transmission.
–recommended meds (this is a change): for treatment naive (first four are integrase strand transfer inhibitor –INSTI-based, fifth is protease-inhibitor — PI-based)
–dolutegravir/abacavir/lamivudine — but remember to make sure first that they are HLA-B*5701 negative as with all abacavir regimens –available as a a fixed-dose single-pill combination, should be taken with food
–dolutegravir plus tenofovir/emtricitabine, should be taken with food
–elvitegravir/cobicistat/tenovovir/emtricitabine — but only for patients with pre-antiretroviral creatinine clearance >70 ml/min. Available as a a fixed-dose combination, should be taken with food
–raltegravir/tenofovir/emtricitabine
–darunavir/ritonivir plus tenofovir/emtricitabine, should be taken with food
–efavirenz was bumped off the primary recommended drug list (though it is cheaper and has great long-term efficacy) because of more adverse effects. Still okay as an alternative. And, no need to change someone doing well and tolerating the drug. Atazanavir was also bumped to the alternative list because of adverse effects (jaundice/hyperbilirubinemia, GI toxicity), neprolithiasis, and a recent trial finding nephrotoxicity similar in degree to tenofovir (and we should not give atazanavir with tenofovir if creat clearance <70 ml/min) . Also atazanavir needs gastric acid to work. I personally have lots of patients on efavirenz-based regimens (reflecting my age, and how long ago most of my patients began therapy), and my experience with atripla is that it works almost universally, accommodation to adverse CNS effects happens the majority of the time, and that it is more forgiving in patients who miss pills than I would have expected (there are even some studies that taking it 5 days/week is okay, though I personally would not recommend that).
–also, in patients unable to take tenofovir or abacavir, can try darunavir/rinonivir plus raltegravir BID (if viral load <100K) or lopinavir/ritonivir BID plus 3TC (these are 2 regimens in the Alternative category, which have only 2 active drugs)
–immunologic failure (low CD4 count with suppressed viral load): also no change — ie, nothing seems to help — adding meds, changing regimens. Focus on modifiable risk factors for chronic disease (smoking cessation, healthy diet, exercise, treating hypertension/hyperlipidemia)
–monitoring: for first 2 years: viral load every 3-4 months, CD4 every 3-6 months; after first 2 years: can extend viral load monitoring to every 6 months if patient consistently with suppressed viral load. Also if CD4 >500 and viral load suppressed consistently, do not need to check the CD4. if CD4 is 300-500, can check CD4 every 12 months [I do have had a patient with consistent virologic suppression, whose CD4 plummeted from 450 range to 200-250 range, but, again, there are no good interventions in this setting]
–acute/recent HIV: pretty much the same as with treatment for naive infections above, thought they note that ART treatment can be initiated prior to getting genotype results, using a pharmacologically-enhanced PI (eg darunavir/ritonavir) with 2 NRTIs (eg tenof/emtricit), since resistance to PIs emerge slowly and clinically significant transmitted resistance to PIs is uncommon.
–HIV-infected women: no overall difference from above, but beware of drug interactions with oral contraceptives (consider alternative contraception) and avoid efavirenz-based regimen (probs with pregnancy/birth defects, though recent studies have not found this to be a problem). Some details: problems mostly with PIs and NNRTIs which either increase or decrease hormone levels , with risk of pregnancy (decreased hormone effect) or thromboembolism (increased effect). Injectable depot-medroxyprogesterone seems okay in small studies. There are some great tables in the full guidelines, esp Tables 19 and 20, which review all of the known drug-drug interactions, including hormonal contraceptives
–HIV-2: new section added. Will defer to document (page I-25) other than to note that NNRTIs don’t work and the PIs that work best are: darunavir, lopinavir and saquinavir. The INSTIs (eg dolutegravir) have potent activity. And there are labs (Univ of Washington and NY State dept of health) which do quantitative HIV-2 viral load testing [I had previously posted on how great the Univ of Washington was, esp Geoffrey Gottlieb, in both running the viral load and resistance testing for one of my patients]
–Hep C coinfections: lots of new data, with more coming in daily. Basically, screen all HIV patients for hep C, and treat the hep C regardless of CD4 count. Given pill burden and potential adverse events, in those presenting with hep c and hiv with CD4<200, might be useful to start HIV rx first, then to hep C when patient clearly tolerates the hiv meds. Having hiv does not seem to diminish efficacy of hep C treatment.
So, these guidelines are really great overall. Although HIV treatment has migrated into the ID/HIV specialty realm (it had become a “primary care disease” in the past, when there were fewer qualified specialists to take care of the burgeoning epidemic…), in many ways it is much easier to take care of HIV patients now than in the past (much better drugs, decreased adverse effects, hugely decreased pill burden) and, with the longer life of HIV patients, they need strong primary care support anyway to deal with other chronic diseases (and even treated HIV seems to predispose to cardiovascular disease and perhaps cancer). And there are important easy-to-use services to help interpret genotypes or make sure everything is on track (I call the free HIV consultation service in San Francisco pretty often when questions come up, and they have experienced clinicians/pharmacists available pretty much right away — 1-800-933-3413)