Antiretrovirals for HIV

(Last Updated 5/4/2021)

David Serota’s Diagram of ART (Great for bringing to rounds with learners!)

Guidelines

• https://hivinfo.nih.gov/
• 2018 HIV resistance testing guidelines (IAS-USA): Gunthard et al. Clin Infect Dis 2019;68(2):177-187.
• 2014 ART for treatment of adult HIV (IAS-USA): Gunthard et al. JAMA. 2014;312(4):410-425.
• 2016 ART for treatment of adult HIV (IAS-USA): Gunthard et al. JAMA. 2016;316(2):191-210.
• 2018 ART for treatment and prevention guidelines: Saag et al. JAMA 2018;320:379-396.
• 2020 ART for treatment and prevention guidelines: Saag et al. JAMA 2020;324(16):1651-1669.
• HIV care quality measures: Horberg et al. Clin Infect Dis. 2010;51(6):732-738.
• Rapid start guidelines: Radix et al.
• Essential components of effective HIV care (HIVMA and Ryan White): Gallant et al. Clin Infect Dis. 2011;53(11):1043-1050.

Review articles

• Triumeq: Grieg et al. Drugs. 2015;75(5):503-514.
• Symtuza: Deeks. Drugs. 2018;78(10):1013-1024.
• Biktarvy: Deeks. Drugs. 2018;78(17):1817-1828.
• Long-term toxicity of ART regimens and implications for an aging population: Chawla et al. Infect Dis Ther. 2018;72(2):183-195.
• Ibalizumab: Blair. Drugs. 2020;80(2):189-196.
• Ibalizumab and fostemsavir in the management of heavily pre-treated patients with HIV: Riccardi et al. Recent Pat Antiinfect Drug Discov. 2018;13(3):190-197.

Systematic Reviews / Meta-analyses

• Intersections of social-ecological factors and HIV stigma in the US south: Ingram et al. J Assoc Nurses AIDS Care. 2019;30(3):330-343.

Trials

• Viral suppression is achieved less often in the real world than in clinical trials; missed clinic visit were an important risk factor for unsuppressed VLs: Lucas et al. Ann Intern Med. 1999;131(2):81-87.
• Engagement with health care provider was associated with better adherence to ART: Bakken et al. AIDS Patient Care STDS. 2000;14(4):189-197.
• Adherence to ART >95% optimized virologic outcomes: Paterson et al. Ann Intern Med. 2000;133(1):21-30.
• Poor retention in care leads to 50% higher mortality: Giordano et al. Clin Infect Dis. 2007;44(11):1493-1499.
• Financial stress is associated with reduced treatment adherence in a resource-rich setting: McAllister et al. HIV Med. 2013;14(2):120-124.
• Missed clinic visits in the first year after initiating ART was associated with more than double the long-term mortality: Mugavero et al. Clin Infect Dis. 2009;48(2):248-256.
• Missed clinic visits in the first year after initiating ART was associated with more than double the long-term mortality: Kay et al. Open Forum Infect Dis. 2019;6(4):ofz120.
• Homelessness at diagnosis is associated with death: Spinelli et al. AIDS. 2019;33(11):1789-1794.
• Receipt of >80% of HIV quality measures is associated with improved survival: Korthuis et al. Clin Infect Dis. 2016;62(2):233-239.
• CASCADE: same-day ART initiation increased linkage to care and viral suppression at 12 months in Lesotho: Labhardt et al. JAMA. 2018;319(11):1103-1112.
• Same-day HIV testing and ART initiation increased retention in care and virologic suppression in Haiti: Koenig et al. PLoS Med. 2017;14(7):e1002357.
• RapIT: same-day ART initiation increased ART update and virologic suppression in South Africa: Rosen et al. PLoS Med. 2016;13(5):e1002015.
• Rapid ART for vulnerable populations is acceptable, feasible and successful in San Francisco Ward 86: Coffey et al. AIDS. 2019;33(5):825-832.
• Rapid entry in Atlanta: Colasanti et al. Open Forum Infect Dis. 2018;5(6):ofy104.
• Continuum of care for rapid ART initiation in New Orleans: Halperin et al. Open Forum Infect Dis. 2019;6(4):ofz161.
• PARTNER: U=U for heterosexual and MSM serodifferent couples: Rodger et al. JAMA. 2016;316:171-181.
• PARTNER2: U=U for gay men in serodifferent partnerships: Rodger et al. Lancet. 2019;393:2428-2438.
• SWITCHMRK 1 and 2: suppressed patients switched from lopinavir/r to raltegravir had increased virologic failure compared to staying on lopinavir/r: Eron et al. Lancet. 2010;375(9712):396-407.
• TAF = TDF (as Genvoya and Stribild) at 48 weeks and TAF had lower renal and bone effects: Sax et al. Lancet 2015;385(9987):2606-2615.
• TAF = TDF (as Genvoya and Stribild) at 96 weeks and TAF had lower renal and bone effects: Wohl et al. J Acquir Immune Defic Syndr. 2016;72(1):58-64.
• Switching to Genvoya in patients with renal impairment was safe and effective: Pozniak et al. J Acquir Immune Defic Syndr. 2016;71(5):530-537.
• Complera = Atripla at 48 weeks in treatment-naive patients, with improved tolerability: Cohen et al. AIDS 2014;28:989.
• Switching to Complera from boosted PI regimens maintained suppression: Palella et al. AIDS 2014;28:335.
• Biktarvy = Triumeq at 48 weeks in previously untreated adults: Gallant et al. Lancet 2017;390(10107):2063-2072.
• Biktarvy = Triumeq at 96 weeks in previously untreated adults: Wohl et al. Lancet HIV. 2019;6(6):e355-e363.
• Biktarvy = dolutegravir + Descovy at 48 weeks in previously untreated adults: Sax et al. Lancet 2017;390(10107):2073-2082.
• Biktarvy = dolutegravir + Descovy at 96 weeks in previously untreated adults: Stellbrink et al. Lancet HIV. 2019;6(6):e364-e372.
• Switch to Biktarvy from Triumeq: Molina et al. Lancet HIV. 2018;5(7):e357-e365.
• Switch to Biktarvy from boosted PI regimens: Daar et al. Lancet HIV. 2018;5(7):e347-e356.
• Switching to Biktarvy in women: Kityo et al. J Acquir Immune Defic Syndr. 2019;82(3):321-328.
• DAWNING: in patients failing first line therapy, switching from lopinavir/r to dolutegravir had better virologic outcomes regardless of resistance: Brown et al. CROI 2019. Seattle, WA. Abstract 144.

• GS 380-4030: DTG and BIC based regimens are effective treatment options for suppressed patients, including those with archived NRTI resistance
  • Sax et al. Clin Infect Dis. 2020
• BRAAVE: Black PLWH with NRTI resistance maintained suppression when switched to BIC
  • Hagins et al. CROI 2020. Abstract 36.

RANDOMIZED SWITCH TO B/F/TAF IN AFRICAN AMERICAN ADULTS WITH HIV

• TANGO: Juluca = continuing current TAF-based ART regimen (switch): van Wyk. Clin Infect Dis. 2020;71(8):1920-1029.
• SWORD-1 and 2: Juluca = continuing current (any) ART regimen (switch): Libre et al. Lancet. 2018;391(10123):839-849.
• Switching from a TDF containing regimen to Juluca improves parameters of bone health: McComsey et al. AIDS. 2018;32:477.
• Study 119: Switch from a 5-tablet regimen to Genvoya/darunavir maintained viral suppression and improved renal safety in patients with 2 or 3 class drug resistance
  • Huhn et al. J Acquir Immune Defic Syndr. 2017;74(2):193-200.
• DRIVE-SHIFT: Switch to Delstrigo (DOR/3TC/TDF) = current regimen in virologically suppressed patients, including those with NNRTI resistance
  • Johnson et al. J Acquir Immune Defic Syndr. 2019;81(4):463-472.
• BRIGHTE: fostemsavir led to a significant decrease in VL vs. placebo in patients with multi-drug resistant HIV
  • Kozal et al. N Engl J Med. 2020;382(13):1232-1243.
  • https://doi.org/10.1056/NEJMoa1902493
• TMB-301: ibalizumab had significant antiviral activity at 25 weeks in patients with multidrug resistant HIV and few treatment options; diminished susceptibility developed in patients who had virologic failure
  • Emu et al. N Engl J Med. 2018;379(7):645-654.
  • https://doi.org/10.1056/NEJMoa1711460
• TMB-311: ibalizumab continued to work at week 48
  • Emu IDWeek 2019 Washington, DC. Abstract 661; Emu B, et al. CROI 2019. Seattle, WA. 485.
• Kaletra-Truvada did not have more adverse birth outcomes than older regimens
  • Rough et al. N Engl J Med. 2018;378(17):1593-1603.
  • https://doi.org/10.1056/NEJMoa1701666
• ART program associated with with reduction in untreated TB in S. Africa
  • Middelkoop et al. Am J Respir Crit Care Med. 2010;182(8):1080-1085.
  • https://doi.org/10.1164/rccm.201004-0598OC
• Efavirenz-based ART regimen can be used with rifampin for treatment of TB
  • Cattamanchi et al. Clin Infect Dis. 2009;48(2):179-185.
  • https://doi.org/10.1086/595689
• Raltegravir-based ART regimen can be used with rifampin for treatment of TB
  • Grinsztejn et al. presented at 19th international AIDS conference 2013
• Drug-resistant HIV can be transmitted but is less common with integrase inhibitors
  • Spertilli Raffaelli et al. J Antimicrob Chemother. 2018;73(9):2480-2484.
  • https://doi.org/10.1093/jac/dky211
• Baseline genotypic testing in treatment-naive patients starting a dolutegravir or bictegravir-based 3 drug regimen has minimal clinical benefit
  • Hyle et al. Clin Infect Dis. 2020;70:1353-1363.
  • https://doi.org/10.1093/cid/ciz372
• Rates of neural-tube defects associated with ART (dolutegravir had slightly increased risk)
  • Zash et al. N Engl J Med. 2019;381:827-840.
  • https://doi.org/10.1056/NEJMoa1905230
• INSIGHT START: it’s better to start ART immediately even when CD4 >500 than waiting until CD4 is <350
  • Lundgren et al. N Engl J Med. 2015;373(9):795-807.
  • https://doi.org/10.1056/NEJMoa1506816

Long-acting Injectable ART

• LATTE: cabotegravir/RPV in treatment-naive patients was effective at 96 weeks (phase 2b)
  • Margolis et al. Lancet Infect DIs. 2015;15(10):1145-1155.
  • https://doi.org/10.1016/S1473-3099(15)00152-8
• LATTE-2: cabotegravir/RPV every 4 weeks or every 8 weeks in treatment-naive patients was effective at 96 weeks (phase 2b)
  • Margolis et al. Lancet. 2017;390(10101):1499-1510.
  • https://doi.org/10.1016/S0140-6736(17)31917-7
• Patients who participated in LATTE-2 had high levels of treatment satisfaction
  • Murray et al. HIV Res Clin Pract. 2019;20(4-5):111-122.
  • https://doi.org/10.1080/25787489.2019.1661696
• ATLAS: cabotegravir/RPV every 4 weeks = current regimen (switch) at 48 weeks; injection site AEs were common but infrequently led to medication discontinuation
  • Swindells et al. N Engl J Med. 2020;382(12):1112-1123.
  • https://doi.org/10.1056/NEJMoa1904398
• ATLAS-2M: cabotegravir/RPV every 8 weeks = every 4 weeks at 48 weeks in treatment-experienced patients
  • Overton et al. Lancet. 2020;396(10267):1994-2005.
  • https://doi.org/10.1016/S0140-6736(20)32666-0
• FLAIR: cabotegravir/RPV every 4 weeks = Triumeq at week 48 in treatment-naive patients; injection site reactions were common
  • Orkin et al. N Engl J Med. 2020;382(12):1124-1135.
  • https://doi.org/10.1056/NEJMoa1909512
• Pooled analysis of ATLAS and FLAIR: cabotegravir/RVP was noninferior to daily oral cART
  • Rizzardini et al. J Acquir Immune Defic Syndr. 2020;85(4):498-506.
  • https://doi.org/10.1097/QAI.0000000000002466

Articles

• 2019 update on drug resistance: Wensing et al. Topics in Antiviral Med. 2019;27(3):111-121.
• Odefsey: Med Lett Drugs Ther. 2016;58(1494):60-61.
• Descovy: Med Lett Drugs Ther. 2016;58(1500):100-101.
• Vemlidy (TAF): Med Lett Drugs Ther. 2017;59(1511):6-8.
• Biktarvy: Med Lett Drugs Ther. 2018;60(1553):132-134.
• Juluca: Med Lett Drugs Ther. 2018;60(1561):e202-204.
• Life expectancy in optimally treated HIV is almost the same as people without HIV
  • Nakagawa et al. Curr Opin Infect Dis. 2013;26:17-25.
• Life expectancy in optimally treated HIV is almost the same as people without HIV
  • Sabinet et al. BMC Med. 2013;11:251.
• Life expectancy in optimally treated HIV is almost the same as people without HIV
  • Nsanzimana et al. Lancet Glob Health. 2015;3:e169-77.
• LIfe expectancy in optimally treated HIV is almost the same as people without HIV
  • Lohse et al. Ann Intern Med. 2016;165(10):749-750.

Podcasts

• Louisville Lectures 11/18/16

Tweetorials

3 high yield NRTI mutations

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Mini-review of three high yield NRTI mutations from rounds today — Keep scrolling for more! pic.twitter.com/Jxb8ZyubPC

— BIDMC Infectious Diseases Fellowship (@BIDMC_IDFellows) June 10, 2020

3 high yield NNRTI mutations

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Mini-review of three high yield NNRTI mutations! Continued learning from yesterday.#IDTwitter #MedTwitter #HIVTwitter pic.twitter.com/3aKKBN1eid

— BIDMC Infectious Diseases Fellowship (@BIDMC_IDFellows) June 11, 2020

2nd & 3rd line therapies

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Thanks Chris Rowley for our core lecture on 2nd+3rd line therapies for HIV! Here are some teaching points from the cases.

First off, ART = daunting list. Take your time, think about the classes as you come up with a regimen, proceed knowing that there is a lot to learn pic.twitter.com/SA8484MXNm

— BIDMC Infectious Diseases Fellowship (@BIDMC_IDFellows) July 24, 2020

Further resistance info (PI, INSTIs, when to test)

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Thanks to Dan Kuritzkes+Suzanne McCluskey for talk on drug resistance today in the HIV core lecture series! @MGHBWHIDFellows #IDFellows @ID_Fellows #IDTwitter

To review high yield mutations, check these prior 🧵

NRTI: https://t.co/FOwPPVR0bZ
NNRTI: https://t.co/3jQfvDhklL

— BIDMC Infectious Diseases Fellowship (@BIDMC_IDFellows) August 14, 2020

M184V mutation

1/ #IDFellows, here's an #IDCase
49M with 25yr h/o HIV and intermittent compliance establishing care after PCP retired. Most recent regimen was TDF/FTC/EFV; he has been taking this 2-3 times a week to make it last. VL 12500, CD4 321. Genotype w/M184V. What would you prescribe?

— Infectious Disease Fellows Network (@ID_fellows) August 20, 2020