New HIV treatment guidelines

The International Antiviral Society - USA Panel just published their 2018 recommendations for antiretroviral drugs in treatment and prevention of HIV infection in adults ( see hiv 2018 treatment guidelines intl antiviral society jama2018 in dropbox or doi:10.1001/jama.2018.8431 or https://jamanetwork.com/journals/jama/fullarticle/2688574 ).

Details:

-- initiating antiretroviral therapy (ART):

    -- start ART therapy as soon as possible after the diagnosis, but do not use an NNRTI because of concerns for drug resistance, or abacavir without 1^st testing for HLA –B*5701; some opportunistic infections may preclude starting ART right away, though it should be started within the 1^st 2 weeks after the diagnosis for most of them. Can be started right away with the diagnosis of malignancy

    -- draw HIV viral load; CD4 count; HIV genotype for NRTI, NNRTI, PI resistance; test for viral hepatitis, comprehensive metabolic panel. Though treatment can be started prior to the results.

    -- begin primary prophylaxis for pneumocystis pneumonia when the CD4 count is < 200

    -- crytococcal  disease prophylaxis is not recommended in highly-resourced settings where the prevalence is low

    -- recommended rapid start therapies:

        --dolutegravir, plus TAF (tenofovir alafenamide) or TDF (tenofovir disoproxil fumarate), plus 3TC (lamivudine) or FTC (emtricitabine)

        --bictegravir/TAF/FTC

        --darunavir/ritonavir, plus TAF or TDF, plus 3TC or FTC

    -- other options when the above agents are not available, drug interactions, etc:

        --darunavir/cobicistat (or ritonavir) plus TAF (or TDF)/FTC [by the way, the FDA just approved a single pill with this combo: darunavir 800mg, cobicistat 1500 mg, emtricitabine (FTC) 200mg and tenofovir alafenamide (TAF) 10mg, under the trade name Symtuza. See https://www.janssen.com/janssen-announces-us-fda-approval-symtuza-dcftaf-first-and-only-complete-darunavir-based-single-0 ]

        --efavirenz/TDV/FTC

        --elvitegravir/cobicistat/TAF (or TDF)/FTC

        --raltegravir plus TAF (or TDF)/FTC

        --rilpivirine/TAF (or TDF)/FTC (but only if the viral load <100,000 copies and CD4 count >200

    --TAF and TDF are similar virologically. TAF has lower plasma levels, is associated with less renal and bone toxicity. These adverse effects of TDF are exacerbated when combined with ritonavir or cobicistat (these increased tenofivir plasma levels)

    -- always check for drug-drug interactions [the best site seems to be https://www.hiv-druginteractions.org/checker ]

    -- pregnancy:

        -- there are recent studies suggesting there may be neural tube defects with dolutegravir, so that should not be used. Raltegravir is the recommended InSTI for women already pregnant.

        -- Atazanavir/ritonavir once daily or darunavir/ritonavir twice-daily are the recommended PIs

        -- abacavir/3TC (or FTC) in those HLA-B*5701 negative, or TDF/FTC (not TAF, insufficient safety data)

    -- baseline bone mineral density (BMD) should be done in postmenopausal women and in anyone older than 50, since HIV itself is associated with osteoporosis and fracture, and patients lose 2-6% of bone mineral density in the 1-2 years after ART initiation. TDF should not be used in patients with osteopenia or osteoporosis

    -- renal failure: dose reduction of 3TC in those at creatinine clearance <50. For those with ESRD on dialysis, studies have shown effectiveness of elvitegravir/cobicistat/TAF/FTC

-- initial ART in those with OIs (will not review all):

    -- for TB: on rifamycin--based therapy: 2 NRTIs (not TAF) plus efavirenz 600mg, raltegravir 800mg BID, or dolutegravir 50mg bid

    --for LTBI: 1 month course of rifapentine plus INH (equivalent to 9 months of INH). Can give with efavirenz-based ART. Once weekly rifapentine/INH is also okay when used with raltegravir. (see http://gmodestmedblogs.blogspot.com/2018/07/updated-ltbi-treatment-with-weekly-meds.html )

-- if switching ARV regimens, remember that ritonavir and cobicistat have different drug-drug interactions with HIV meds

-- there are small studies suggesting that patients can be switched to dual therapy [especially if well-controlled on regular therapy for a while. Initiating therapy with these regimens is being studied now]:

    -- can be a boosted PI (lopinavir, atazanavir, or darunavir) and 3TC; study show effectiveness for up to 2 years

    -- dolutegravir plus 3TC; studies show effectiveness for 48 weeks

--Laboratory monitoring:

    --at HIV diagnosis: HIV RNA test (viral load), CD4, HIV genotype, HLA-B*5701 (if intending abacavir), co-infections (TB, STIs, hepatitis, Pap)

    --during ART: viral load within 6 weeks of starting ART, then q3 months until <50 for one year, then q6 months; CD4 q6 months til >250 for 1 yr, then stop if viral load suppessed; monitor appropriately for co-infections

    --if HIV VL rises to >50, then recheck in 4 weeks. virologic failure is if >200 on 2 consecutive measurements (refer to the document for suggestions about changing ART regimens for virologic failure)

    --if VL remains in the 50-200, not clear what to do, but would reinforce med adherence and not intensify the regimen

--Prevention: (will only comment on PrEP, not on other prevention topics). See http://gmodestmedblogs.blogspot.com/2015/12/on-demand-hiv-pre-exposure-prophylaxis.html   

    --recommended for populations with HIV incidence >2% or HIV-seronegative partners of HIV-infected persons “who are not consistently virally suppressed” [my approach will still be to suggest PrEP even if virally suppressed.  One just never knows…. And getting HIV, though not what it used to be, probably is still best avoided….]

    --typical regimen is TDF/FTC daily, recommended to begin 1 week before beginning sex, and if to be discontinued, until one week after

    --“on-demand”/event-driven, if infrequent sexual exposure: 2 tablets (best if closer to 24 hours prior to sex than the 2-hour time-frame), then 1 pill daily for 2 days

    --not do other regimens (including TAF)

    --not use if eGFR<60

    --check HIV antigen-antibody within 7 days of starting PrEP (though may need viral load to exclude acute HIV infection if high-risk). Check HIV and STI screening every 3 months

    --acute HIV infections can be hard to pick up (PrEP can delay antibody response and decrease viral loads). If test positive, confirm viral load and genotype testing [resistance has been observed rarely]

Commentary:

--there are a few notables in the above guidelines:

    --starting HIV meds right away, even before initial blood tests back (this is based on studies showing that starting right away, if patient amenable, seems to lead to increased med adherence later), unless concurrent OI which precludes that [and, of course, make sure you can get in contact with the patient if there is an abnormal blood test which precludes using the chosen med]

    --changes in the 3 preferred regimens to ones that are well-tolerated, have high barriers to resistance, do not include a boosting agent (ritonavir and clobicistat have lots of drug-drug interactions, as well as boosting the price) and have low pill burden.

    --no need for prophylaxis against Mycobacterium avium complex (MAC) or Cryptococcus in many countries

    --more specific guidelines on bone mineral density monitoring, which really makes sense in these days of TAF

    --no need to continue checking CD4 counts in those virally suppressed for 1 year and CD4 >250

    --there is a viable alternative of 2-pill therapy when patients are well-controlled on one of the initial regimens [I did this recently with one patient who had adverse effects on both tenofovir and abacavir, using dolutegravir and 3TC.  So far so good]

--I personally have been using Biktarvy (bictegravir/emtricitabine/TAF) as my initial drug of choice. works well/rapid decline in viral load. Few adverse effects. high barrier to resistance. one pill. No more expensive than the dolutegravir regimens. Easy insurance company approval.  See http://gmodestmedblogs.blogspot.com/2018/04/hiv-guidelines-new-combo-pill-gets-top.html  

--it is quite disconcerting that there are continued pockets of increased HIV outbreaks. For example, in the 7/26/18 Boston Globe, there was a report of an outbreak in Lawrence and Lowell with 129 new cases among injection drug users since 2015. See http://edition.pagesuite.com/popovers/article_popover.aspx?guid=829f4886-459f-4594-beee-c160f2cfe2bb

geoff​

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