HIV treatment/prevention guidelines 2020
New HIV guidelines for the treatment and prevention of HIV in adults were just released from the International Antiviral Society -- USA panel (formerly the AIDS Society -- USA), an update from their 2018 guidelines (see hiv guidelines antiviral society jama2020 in dropbox or doi:10.1001/jama.2020.17025)
Will review some of the important new recommendations, as well as the kernel of some of the older recommendations
Details:
-- all with HIV and detectable viremia should be treated, independent of the CD4 count (no change from prior recommendations), with immediate entry into care, including a strategy to start ART within 7 days after diagnosis, even on the same day at the 1st clinic visit [I personally tend to repeat the test before starting therapy, just make sure that the lab test was accurate and not a mix-up, unless there is a compelling reason to start therapy immediately]. And ART should be started within 2 weeks after initiation of treatment for most opportunistic infections
-- treatment options (all of the preferred regimens include integrase strand transfer inhibitors, InSTIs (eg, dolutegravir and bictegravir):
-- bictegravir/tenofovir alafenamide (TAF)/emtricitabine (FTC), a single pill Biktarvy
--dolutegravir, plus
-- TAF/FTC
-- Tenofovir disoproxil fumarate (TDF)/FTC
-- TDF/lamivudine (3TC)
-- but, overall, TAF is preferred over TDF, since there are fewer problems with proximal renal tubular toxicity and reductions in bone mineral density, though TAF is associated with more weight gain than TDF. And TDF may become significantly less expensive through generic formulations
-- the 2-drug regimen: dolutegravir/3TC [though should not be done as rapid start, needs baseline laboratory evaluation for resistance to both drugs; nor appropriate in those with chronic hepatitis B or HIV RNA >500,000 copies per mL. Also , they are wary to start with the CD4 count <200 (only small numbers of such patients were involved in the studies, and they seem to have had a less impressive reduction in their viral loads). Not indicated for those being treated for an active opportunistic infection, and needs closer monitoring for adherence and virologic response
-- it is reasonable to switch to a 2-drug regimen as a means to simplify the initial regimen in those without virologic failure or evidence of drug resistance. Another option is dolutegravir/rilpivirine in those without hepatitis B infection (this combination was associated with improvement in bone mineral density, reduced bone turnover, and improved kidney tubular function). Other studies have found that a boosted PI (lopinavir, atazanavir, or darunavir) and 3TC were noninferior to 3-drug regular regimens in maintaining viral suppression in small studies. Again, not to be used in those with hepatitis B
-- long-acting injectable combination cabotegravir and rilpivirine every 4 and potentially every 8 weeks, after a 4-week induction with the oral forms of these meds. This was noninferior to remaining on stable, virologically suppressive regimens based on InSTIs, NNRTIs, or PIs. Injection site reactions are common but generally mild to moderate, and injections were preferred by most participants. A higher dose regimen (600 mg cabotegravir or 900 mg rilpivirone given every 8 weeks) was reported to be noninferior to the 4-week dosing schedule (though 1.5% of people did have virologic failure in the 8-week group, some with rilpivirine and some with InSTI resistance). The combination injection may be very useful for many patients, including those having problems with medication adherence, but this therapy is pending approval by regulatory bodies and availability
-- it is important to check HIV viral load one month after switching any regimens
-- they do not recommend using elvitegravir, since it is co-formulated with Cobicistat and leads to more drug-drug interactions. See below for more comments on this.
-- In the setting of raltegravir or elvitegravir resistance, dolutegravir should be dosed twice-daily with at least one fully active other agent
-- see the article for recommendations for medications in the setting of opportunistic infections
-- during pregnancy: they recommend dolutegravir along with TAF/FTC, since subsequent data from an early study did not find an increased risk of neural tube defects over time, this regimen is more effective than the older efavirenz-based regimen, and TAF was associated with fewer adverse pregnancy or infant outcomes than TDF (these last 2 recommendations about the apparent safety of dolutegravir and the benefit of TAF/FTC over TDF/FTC were both presented only as a poster session or abstract this year). Bictegravir does not have sufficient data for a recommendation. For nonpregnant women of childbearing potential, they should understand that dolutegravir may have a very small excess risk of neural tube defects and that folate supplementation is important in those trying to become pregnant [all women attempting pregnancy should be on folate, especially so for those on dolutegravir]. Women who were taking dolutegravir at the time they become pregnant do not necessarily have to switch ART. Other recommended regimens during pregnancy include raltegravir, atazanavir/ritonavir, darunavir/ritonavir, efavirenz; all would be combined with TDF/FTC or TDF/3TC, with less data supporting TAF combinations
-- for treatment of latent TB infection: is important to check for drug-drug interactions, and that these are different for rifampin and rifapentine [one great site to use is https://www.hiv-druginteractions.org/checker ]
-- lab evaluation: the usual suspects (HIV antibody, viral load, CD4, STI and viral hepatitis screening, tuberculosis screening, HIV genotype at diagnosis), also cryptococcal antigen if CD4 < 100, and HIV integrase genotype only if partner has a failing ART regimen that includes an InSTI. For those who are likely to start abacavir regimens, HLA-B*5701 should be tested prior to starting abacavir [i would consider HIV integrase genotype more broadly in those with partners to be on InSTIs, since the partner may not be aware or disclose resistance; and patients newly put on and InSTI-based regimen who have resistance could then develop resistance to the other ART meds incorporated into the regimen]
-- all people who have had sexual relations, or injected drugs should be tested for HIV at least once; those with ongoing risk should be assessed regularly; and MSM, transgender persons, people injecting drugs outside of needle sharing programs, and people newly diagnosed with STIs or hep C should be tested every 3 months for as long as risk continues (screening should include tests that detect recent HIV infections, including the combined HIV antibody and antigen test or HIV viral load) [i personally would do risk assessment for MSM and transgender people instead of automatically doing q3month testing...]
-- those with a high-risk exposure in the prior 72 hours should have lab tests for creatinine, hepatitis B surface antigen, STIs, and the combo HIV antibody/antigen test or HIV viral load; though postexposure prophylaxis should not be delayed while awaiting these results
-- age- and risk-appropriate screening should be done for STIs at exposed mucosal sites, anal and cervical dysplasia, tuberculosis, general health issues, and medication toxicity. Hep C screening is recommended at least yearly for persons with ongoing risk.
-- When viral suppression is achieved and maintained, CD4 count should be measured every 6 months until measurements are >250 for at least one year. Thereafter, CD4 counts do not need to be measured unless ART failure is identified (i.e. by viral load) or if the patient experiences an immunosuppressive condition
-- HIV prevention: there is a long section on postexposure prophylaxis (PEP) as well as preexposure prophylaxis (PrEP), highlighting the importance of both and reinforcing the need to discuss PrEP with all sexually active adults and adolescents as well as individuals who inject drugs (see document for more details about management and testing)
-- there are still about 40,000 new cases of HIV in the US per year, largely in the South
-- for MSM, a double dose TDF/FTC is recommended in the 1stday; and it is okay to prescribe the 2-1-1 dosing method (2 pills 2-24 hours prior to sex, a single pill 24 hours later, and a final those 24 hours after that; see http://gmodestmedblogs.blogspot.com/2015/12/on-demand-hiv-pre-exposure-prophylaxis.html )
- the long-acting injectable cabotegravir 600 mg every 8 weeks, pending approval by regulatory agencies and availability, is recommended for PrEP for cis-gender men and transgender women who have sex with men
-- for PEP: a 3-drug ART regimen is recommended, preferably within the 1st 24 hours but up to 72 hours after exposure and continued for 28 days; if HIV is acquired during PrEP, transition to dolutegravir or bictegravir or ritonavir-boosted darunavir-based regimens is recommended
-- aging and HIV: Lots of new studies related to an aging population in the setting of effective ART, noting that those in their 6 and 7th decade of life are at higher risk of poor health outcomes, despite achieving durable viral suppression. There is an increased risk of cardiovascular disease, CKD, neurocognitive impairment, frailty and polypharmacy, and mental health disorders (and cancer, though not mentioned??). Also, social concerns about isolation, loneliness, and stigma
-- cost of medications: can be extraordinarily high in resource-rich countries (up to $48,000 per month, though the same medications cost $27 per month in resource-limited countries). [But non-affluent people in resource rich countries who live in areas with inadequate affordable healthcare can have a substantial barrier to appropriate care]
Commentary:
-- i am very concerned about boosted-HIV regimens, those using cobicistat and ritonavir. these boosters are associated with lots of drug-drug interactions, since they profoundly inhibit the P450 system. And, especially as those with HIV age and likely need more meds for their accumulating comorbidities, more and more problems might happen. There have been several case reports of people on these meds, then getting even topical steroids (intraarticular or inhaled), then developing severe and prolonged Cushings (see http://gmodestmedblogs.blogspot.com/2019/05/hiv-meds-local-steroids-and-cushings.html ). so, in light of the presence of fantastic HIV regimens not requiring these boosters, i personally am not prescribing boosted regimens (including genvoya, which includes elvitegravir, cobicistat, TAD and FTC; or the boosted PI regimens) unless the patient is unable to take others, and am trying to migrate those on these meds to a non-boosted regimen. A real concern with the boosted regimens is the high potential for error: those going into urgent care centers and getting an inhaled steroid, or those seeing an orthopod/rheumatologist/primary care for a steroid injection may be end up with Cushings...
--the one adverse effect of InSTIs that i am seeing pretty regularly is weight gain, an issue for many people. and my preferred initial med (just one pill) is biktarvy (bictegravir/TAF/FTC), and the TAF seems to be more associated with weight gain than TDF. i have switched a few people to the combo of dolutegravir/3TC with good virologic effect. maybe those gaining too much weight on biktarvy will do better with dolutegravir/3TC?? i don't have sufficient experience or know of appropriate studies to be sure.-- Covid-19: so far, small studies have suggested that there is no difference in clinical outcomes in those with HIV vs the non-HIV population, though the results are inconsistent. One study found that those with CD4 counts <200, despite virologic suppression, had a higher risk of poor outcomes. See https://journals.lww.com/aidsonline/Fulltext/2020/10010/Clinical_characteristics,_risk_factors,_and.11.aspx? or https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf, page 218). Some other studies have found poorer outcomes overall with those with HIV infection,, esp younger people (eg https://www.medrxiv.org/content/10.1101/2020.08.07.20170449v1 ). There also is a suggestion that people with HIV are at lower risk of acquiring Covid. But we really don’t have clear studies: there aren’t great community-based data on the coexistence of HIV and Covid (mostly just hospitalized patients), the decreased incidence of Covid in patients with HIV perhaps might be explained by the fact that people with HIV overall may be more cautious about the spread of a viral illnesses?? But, it does not seem that those with HIV are largely different from the background population in terms of Covid
so, useful HIV guidelines, as always. the probable addition of the monthly injection will be welcome as a primary treatment alternative (and these injections did have great acceptance in the studies)
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