HIV/AIDS 2024 (PDF)

Human Immunodeficiency Viruses and Acquired Immunodeficiency Syndrome PPR 6670 November 12th-14th, 2024 Don Branam Pharm.D., BCPS, FASHP Objectives Define the etiology and epidemiology of HIV Illustrate the life cycle of HIV Describe...

Human Immunodeficiency Viruses and Acquired Immunodeficiency Syndrome PPR 6670 November 12th-14th, 2024 Don Branam Pharm.D., BCPS, FASHP Objectives Define the etiology and epidemiology of HIV Illustrate the life cycle of HIV Describe the pathophysiology of AIDS Compare and apply the pharmacology of antiretroviral therapy Classify the toxicities and adverse effects of antiretroviral therapy Describe the drug-drug interactions of antiretroviral therapy Identify after reviewing the vaccine recommendations which vaccines patients living with HIV should and should not receive Summarize preferred starting regimens that may be considered for patients, either newly diagnosed or in other situations, with HIV/AIDS Special populations Define prophylactic regimens for post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) Human Immunodeficiency Viruses Also known as HIV-1 and HIV-2 Causative pathogens for Acquired Immunodeficiency Syndrome (AIDS) HIV-2 also causes AIDS but is less virulent, transmissible and prevalent than HIV-1 HIV is a retrovirus (RNA virus that is transcripted to DNA) Epidemiology Epidemiology Person(s) Living With HIV/AIDS (PLWHA) Since 1981: 85.6 million people have become infected with HIV 40.4 million have died Diagnosis Confirmation of HIV positive status and an AIDS defining illness Confirmation of HIV positive status and CD4 cell count less than 200 CD4 cell is a type of T lymphocyte that is involved in early recognition and protection against infections https://www.unaids.org/en/resources/fact-sheet Accessed Nov 3rd, 2023 HIV/AIDS Timeline 1981 – CDC publishes a report of 5 previously healthy gay men in Los Angeles who had contracted a rare lung infection called Pneumocystis carinii. The patients had other rare infections also. Two of the men died before the report was published. Newspapers picked up the report, and within days, the CDC was flooded with similar reports. Also, the CDC began to receive reports of gay male patients who have a rare cancer called Kaposi’s sarcoma. By the end of the 1981, the CDC had reports of 270 similar cases, and 123 of those patients had died. It’s important to note that this is when suspicions were aroused regarding a new illness. Researchers believe patients were ill from HIV/AIDS in the early 1970s, but it wasn’t recognized HIV/AIDS Timeline 1982 the term “Acquired Immunodeficiency Syndrome (AIDS)” is coined. First report of AIDS related to a blood transfusion First reports of perinatal transmission First money appropriated by Congress for research 1983 First reports of transmission to female sexual partners of males with AIDS CDC reports greatest risk in homosexual males, IVDAs, Haitians, and hemophiliacs First suggestions of a retrovirus called Lymphadenopathy Associated Virus as the cause of AIDS https://goo.gl/images/YqZHFw HIV/AIDS Timeline 1986 First drug to treat HIV/AIDS approved, zidovudine (AZT) HIV/AIDS Timeline 1987 A federal judge ordered 3 HIV-positive brothers who had contracted the virus through blood transfusions to be allowed to return to school. In protest, parents kept their children from school, and someone burned the brothers’ home. At this point, there are 562,000 patients living with HIV in the US HIV/AIDS Timeline 1990 First report of transmission of HIV through a dental procedure Ryan White dies Congress enacts Ryan White CARE Act, which allocates $220 million for AIDS research https://goo.gl/images/8AMbzx https://goo.gl/images/pSWDZm HIV/AIDS Timeline 1992 AIDS becomes the #1 cause of death for US men aged 25-44 There are 754,000 patients living with HIV in the US 1993 Female condom approved First major Hollywood film about HIV/AIDS, “Philadelphia” released, starring Tom Hanks 1994 AIDS becomes the leading cause of death for all Americans aged 25-44 US government recommends that pregnant women with HIV be given AZT to reduce perinatal transmission HIV/AIDS Timeline 1995 First protease inhibitor approved Eric Lynn Wright, aka Easy-E, dies from AIDS related illness 1996 Effectiveness of Highly-Active Anti-Retrovial Therapy (HAART) established Number of new cases declines AIDS is no longer the leading cause of Americans aged 25-44, but remains so for African Americans in this age group Viral load test approved First non-nucleoside reverse transcriptase inhibitor (nevirapine) approved HIV/AIDS Timeline 1997 HAART becomes standard of care First combo product approved, Combivir First reports of resistance to HIV meds There are 792,000 people living with HIV in the US UN estimates as many as 30 million people in the world have HIV (most aren’t aware) HIV/AIDS Timeline 1998 First HAART guidelines published CDC reports mortality in African Americans living with AIDS 10 times higher than in Whites and 3 times higher than Hispanics US Supreme Court rules that the Americans with Disabilities Act applies to patients living with HIV/AIDS 1999 WHO announces that AIDS is the 4th leading killer worldwide, and leading killer in Africa HIV/AIDS Timeline 2002 There are 961,000 people living with HIV in the US 2003 CDC states that 27,000 of the 40,000 new infections result by transmission from persons who do not know they are infected Pres. George W. Bush announces President’s Emergency Plan for AIDS Relief (PEPFAR) to spend $15 billion in combating AIDS in underdeveloped countries. HIV/AIDS Timeline 2007 CDC reports over 565,000 people have died of AIDS in the US since 1981 There are 1,113,800 patients living with HIV in the US 2008 PEPFAR re-authorized for additional $40 billion CDC reports over 56,000 new infections each year 2009 100th ART drug released HIV/AIDS Timeline 2010 Pres. Obama signs the Affordable Care Act, with gives special protections to patients living with chronic infections such as HIV NIH announces result of iPREx study, which shows that a daily dose of HIV drugs reduced the risk of HIV infection among HIV-negative MSM 2011 CDC announces 2 separate trials that demonstrate a daily dose of HIV drugs reduced the risk of HIV infection from heterosexual contacts CDC reveals that of 1.2 million people living with HIV, 1 in 5 do not know they are infected, and only 1 in 4 are taking ART meds regularly and have their virus under control HIV/AIDS Timeline 2012 Kaiser Family Foundation release results of a study showing that roughly 25% of Americans believe HIV can be contracted by sharing a drinking glass – almost exact the same share as in 1987 Truvada approved for PrEP CDC initiates a pilot project to train pharmacists and retail store clinic staff at 24 rural and urban sites to deliver rapid HIV testing There are 1,218,000 people living with HIV in the US UN announced that worldwide 1.6 million people died of AIDS HIV/AIDS Timeline 2013 NIH reveals “the Mississippi baby,’ a well documented case of an HIV-infected child who appeared to have been cured of HIV without ART Sec. of State John Kerry announces that, thanks to PEPFAR, 1 million babies have been born HIV-free since 2003 Researchers announce that 2 HIV-positive patients who had bone-marrow transplants were apparently HIV free for weeks since their ART meds were stopped PEPFAR re-authorized; 10-year anniversary 2014 Affordable Care Act goes into effect, and insurers are barred from discriminating against customers with pre-existing conditions such as HIV/AIDS The 2 patients believed to have been cured by bone-marrow transplants relapsed “The Mississippi baby” now has detectable levels of HIV HIV/AIDS Timeline 2015 CDC announces that more than 90% of new HIV infections could be prevented by diagnosing people living with HIV and ensuring they receive treatment Results from START study indicates that HIV-positive patients who start ART before their CD4 counts decrease have a considerably lower risk of developing AIDS or opportunistic infections or illnesses 184 cases of HIV linked to IV drug abuse in Indiana HIV/AIDS Timeline 2016 Overall lifetime risk of HIV diagnosis in US 1 in 99 HIV Origins Scientists believe HIV mutated from Simian Immunodeficiency Virus (SIV), which is found in certain species of chimpanzees in Central Africa Humans contracted SIV when hunted chimpanzees for meat and came into contact with infected blood May have started in the late 1800s First verified case was 1959 in the Democratic Republic of the Congo 2023 39.9 million persons living with HIV globally 37.5 million adults 15 years or older 1.4 million children 0-14 years 53% women and girls 86% are aware of their HIV status 30.7 million people were accessing antiretroviral therapy 1.3 million new infections, all ages 630,000 deaths Since 1981, globally 88.4 million people have become infected with HIV/AIDs, and 42.3 million people have died https://www.unaids.org/en Accessed Nov 10th, 2023  https://www.tn.gov/health/health-program-areas/statistics/health-data/hiv-data.html Accessed Nov 6th, 2023 Info for the exam starts here! http://webarchive.nationalarchives.gov.uk/+/http://www.dwp.gov.uk/medical/med_conditions/images/course-hiv-infection.jpg Accessed March 10th, 2018 https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle Accessed 3/10/18 3a. Capsid containing HIV RNA and enzymes penetrates CD4 cell nucleus 3b. Capsid dissolves 7a. New capsid forms and surrounds HIV RNA and enzymes https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle Accessed March 10th, 2018 Preventing Transmission of HIV Homosexual or heterosexual Risk increases with increased number of partners Prevention Latex condoms Circumcision Pre-exposure prophylaxis (PrEP) Diagnosis All patients ages 13-64 years of age should be screened for HIV risk HIV testing using recommended 3 step process 4th generation HIV antigen/antibody test If negative, patient does not have HIV If positive, then: Confirmatory testing for HIV-1 and HIV-2 If indeterminate, do HIV viral load measurement AIDSinfo.nih.gov Accessed March 5th, 2020 Primary Infection About 50% of patients develop symptoms Develops 2-4 weeks after infection Duration 3-14 days Symptoms: Fevers, sweats, lethargy, malaise, arthralgias, headache, photophobia, diarrhea, sore throat, lymphadenopathy Antiretroviral Therapy (ART) Formerly known as Highly Active Anti-Retroviral Therapy (HAART), but this is an obsolete term Distinct Classes: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (“Nukes”) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (“Non-Nukes”) Protease Inhibitors Integrase Inhibitors Capsid Inhibitors Fusion Inhibitors CCR5 Inhibitors NRTIs Work by inhibiting viral reverse transcriptase, thereby preventing viral DNA from being formed Effective against HIV-1 and HIV-2 Examples Zidovudine (AKA azidothymidine) – AZT or ZDV, brand Retrovir Myelosuppression, myopathies Still used widely to prevent vertical transmission Lamivudine – 3TC, brand Epivir Abacavir – ABC, brand Ziagen Tenofovir disoproxil fumarate – TDF, brand Viread Emtricitabine – FTC, brand Emtriva Tenofovir alafenamide – TAF, brand Vemlidy https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle Accessed March 10th, 2018 Selected NRTIs Lamivudine Abacavir Tenofovir disoproxil fumarate Emtricitabine Tenofovir alafenamide All NRTIs have a risk for lactic acidosis and All NRTIs require intracellular phosphorylation to become pharmacologically active Lamivudine 3TC (Epivir) Also has activity against hepatitis B When used as the sole active hep B agent, resistance develops quickly 40% and 90% at 2 and 4 years, respectively To prevent resistance, combine with TDF or TAF Most common ADE is headache, followed by diarrhea, nausea, abdominal pain, insomnia Package labeling says dose reduction necessary for CrCl < 50 mL/min – ID experts disagree and do not adjust for those patients Fischetti and colleagues evaluated full dose 3TC (300 mg daily) in patients across all ranges of renal function and found the dose was well tolerated OFID, Volume 5, Issue 10, October 2018, ofy225 Abacavir ABC (Ziagen) Lipid abnormalities Associated with increased risk of MI Studies vary Only NRTI that, based on package labeling, doesn’t require renal dose adjustment Avoid in advanced hepatic impairment Hypersensitivity reactions are possible Must determine HLA-B*5701 status Patients who are positive must not receive abacavir Tenofovir Disoproxil Fumarate (TDF) TDF (Viread) Pro-drug Tenofovir is released on first pass, resulting in higher systemic concentrations of tenofovir, thus higher ADEs Renally eliminated ADEs GI toxicity Renal dysfunction Bone demineralization Osteopenia/osteoporosis Emtricitabine FTC (Emtriva) Renally eliminated Structurally similar to Lamivudine Same concerns for emergence of resistance for Hep B when FTC is the sole active agent (see the slide for 3TC) ADEs Diarrhea, nausea, headache, rash Pigmentation changes on palms and soles in non-white patients (rare) Tenofovir Alafenamide (TAF) TAF For HIV, only available in combo products Pro-drug Pro-drug stays intact longer, and tenofovir is released intracellularly, thus fewer ADEs Lower incidence of renal dysfunction and bone demineralization compared to TDF ADEs Increased lipids Weight gain, especially when combined with DTG (Dolutegravir) NNRTIs Bind noncompetitively to reverse transcriptase, resulting in a conformational change to the enzyme No activity against HIV-2 Only a single mutation in HIV can confer resistance (“low genetic barrier”) Overall, use of this class is on the decline Class ADEs Rash, hepatotoxicity Lots of DDIs Gastric acid suppressors Cyp P450 NNRTIs Efavirenz – EFV (Sustiva) ADEs – sedation, vivid dreams, depression, lipid abnormalities, rash, suicide Take on an empty stomach HS to sleep through CNS effects Nevirapine – NVP (Viramune) Rash, GI toxicity, hepatotoxicity, SJS Worst in class Mollan K Ann Intern Med 2014;1611-19 NNRTIs Rilpivirine – RPV (Edurant) Rash, depression, insomnia, headache Does not induce or inhibit CYP450 enzyme BUT – can affected by CYP P450 inducers Anti-convulsants phenytoin, carbamazepine, oxcarbazepine, phenobarbital rifampin, rifapentine, St. John’s wort PPIs/H2RAs/Antacids All reduce concentrations of rilpivirine PPIs Absolute contraindicated H2RAs – separate 12 hours before or 4 hours after rilpivirine Antacids – separate 2 hours before or 4 hours after rilpivirine Do not use if Viral Load > 100,000 copies/mL and/or CD4 < 200 Take with a meal and water (do not take with a protein drink) NNRTIs Doravirine DOR (Pifeltro) Approved by FDA 2018 100mg daily with or without food Fewer ADEs Improved lipid profile Lower incidence of rash Fewer CNS ADEs compared to efavirenz Fewer DDIs In particular with acid-suppressing agents Does not induce or inhibit Cyp P450 enzymes Higher genetic barrier than other NNRTIs Protease Inhibitors Inhibit a key enzyme in the viral maturation process, resulting in immature, noninfectious virions Poor or erratic absorption complicates use of these agents Take with food Dose adjustments required in hepatic insufficiency High genetic barrier Almost always prescribed with Cyp 3A4 inhibitors to “boost” systemic concentrations Boost with ritonavir or cobicistat Class ADE – endocrine disturbances such as insulin resistance, lipodystrophy (peripheral fat loss and central fat accumulation,) lipid abnormalities https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the- hiv-life-cycle Accessed March 10th, 2018 https://goo.gl/images/QzCdBp https://goo.gl/images/3z9fXo PIs Always given with a booster (ie, ritonavir, cobicistat) Atazanavir – ATV (Reyataz) Hyperbilirubinemia – reversible, does not require discontinuation H2 blockers, PPIs, and antacids decrease concentrations Darunavir – DRV (Prezista) Rash, hepatoxicity PIs Ritonavir – RTV (Norvir) Most important to know; used as a “booster” in combinations Potent inhibitor of 3A4 and 2D6 GI intolerance, circumoral and peripheral parasthesias, dysgeusias, asthenia, hyperlipidemia Integrase Strand Transfer Inhibitors INSTIs, or “Integrase inhibitors” for short Bind to HIV integrase, thus inhibiting incorporation of viral DNA into host DNA Use with caution in advanced hepatic insufficiency High genetic barrier Bictegravir, dolutegravir, cabotegravir > raltegravir, elvitegravir ADEs Rash Nausea Headache Psych – anxiety, insomnia, depression, suicidal ideation (rare) Usually in patients with preexisting conditions Weight gain Class effect As much as 10 kg Women > men https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle Accessed March 10th, 2018 Integrase Inhibitors Class effect DDI – separate from polyvalent cations Associated with virologic failure Separate at least 2 hours before or at least 6 hours after polyvalent cations Integrase Inhibitors Raltegravir – RAL (Isentress) Nausea, headache, diarrhea, pyrexia, CK elevation (myopathy, rhabdo) PROs: Longest safety experience Fewest DDIs of the integrase inhibitors CONs: More complex regimen than other integrase inhibitors Cannot be co-formulated with other ARTs Low genetic barrier Don’t administer with aluminum/magnesium-based antacids at all. Use alternative agents Integrase Inhibitors Elvitegravir - EVG (Vitekta) Co-formulated with cobicistat, a potent Cyp 3A4 inhibitor Cobicistat can cause a benign increase in SCr Many interactions with 3A4 substrates Discontinue for severe hepatic insufficiency (Child-Pugh class C) Low genetic barrier Separate from aluminum/magnesium-based antacids by more than 2 hours Integrase Inhibitors Dolutegravir – DTG (Tivicay) Insomnia, diarrhea, benign increases in serum creatinine Weight gain, especially with TAF High genetic barrier DDI - Reduces renal clearance of metformin Watch for hypoglycemia, lactic acidosis Start with lowest dose of metformin and titrate according to glucose No CYP450 interactions Separate from aluminum/magnesium-based antacids 2 hours before or 6 hours after Metabolism is induced by carbamazepine and phenobarbital Possibly phenytoin also? https://programme.aids2018.org/PAGMaterial/PPT/6339_8312/DTG NTD_AIDS2018_FINAL.pptx Accessed Mar 3 2019 Integrase Inhibitors Bictegravir BIC Always Co-formulated with TAF, and FTC (Biktarvy) Only available formulation as of January 2023 High genetic barrier Once daily dosing Only if CrCl >/= 30 mL/min Watch for benign increases in serum creatinine (same as DTG, EVG) Administer 2 hours before aluminum/magnesium-based antacids ADEs Nausea, diarrhea, headache, weight gain Integrase Inhibitors Cabotegravir - CAB PO tablets - Brand name Vocabria ADEs: headache, nausea, abnormal dreams, anxiety, insomnia, depression, hepatotoxicity Injection – Brand name Apretude Only indicated for PrEP (CAB-LA) ADEs: as with PO; IM site reactions Co-formulated with rilpivirine into a long-acting IM injection that is given once per month Brand name Cabenuva Not for treatment naïve patients (pts NOT started treatment for HIV yet) Pts must first achieve viral suppression with a preferred regimen (pts viral load need to undetectable) Must maintain viral suppression with cabotegravir plus rilpivirine tablets (Oral-PO) for 3-6 months, THEN May initiate once monthly (IM injection) Cabenuva Pts must be engaged with their health care and agree to make frequent clinic visits to receive injections Capsid Inhibitors Three step MOA (see purple arrows on next slide) 1. Prevents transport of HIV RNA and enzymes into cell nucleus 2. Binds to HIV capsid and stabilizes it, preventing it from dissolving and releasing HIV RNA and enzymes 3. Prevents capsid assembly in final step of maturation process, therefore mature virus cannot form Lenacapavir Tablet and SQ injection Requires an oral loading dose before transitioning to SQ injection Indicated in combo with other ARTs in heavily treatment-experienced pts who are failing current therapy CI’d with strong 3A4 inducers 3a. Capsid containing HIV RNA and enzymes penetrates cell nucleus 3b. Capsid dissolves 7a. New capsid forms and surrounds HIV RNA and enzymes https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle Accessed March 10th, 2018 Entry Inhibitors Fusion Inhibitor Enfuvirtide – T-20, brand Fuzeon Inhibits envelope fusion of HIV-1 but not HIV-2 Low genetic barrier SQ injection ADEs Injection site reactions (pain, erythema, nodules) extremely common (~100%) Hypersensitivity reactions Pneumonia https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle Accessed March 10th, 2018 Entry Inhibitors CCR5 antagonist Maraviroc – MVC (Selzentry) Must determine that the virus attaches to this receptor (tropism test) Work if virus has R5 CD4 receptor (on virus) only; won’t work against X4 CD4 cells Resistance may develop slowly Patients may be at greater risk of infection by flaviviruses (eg, West Nile) DDIs ADEs Rash, abdominal pain, musculoskeletal complaints, pyrexia, orthostatic hypotension Hepatatoxicity Entry Inhibitors Ibalizumab - uiyk Monoclonal antibody that binds to domain 2 on CD4 cell and interferes with HIV-1 entry into host cells; activity against R5 and X4 viruses IV infusion Used for heavily treatment-experienced adults with MDR HIV-1 and are failing their current regimen – resistance treatment ADEs: Diarrhea, dizziness, nausea, rash Entry Inhibitors Fostemsavir PO Prodrug of temsavir Binds near CD4 receptor binding site and prevents conformational changes, thus preventing HIV from entering CD4 cells Salvage therapy for heavily treatment-experienced patients – Last reserved treatment after using all ART and become resistance ADEs QT prolongation DDIs – metabolized by 3A4 https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the- hiv-life-cycle Accessed March 10th, 2018 DDIs with Statins (CYP 3A4 inhibitor) Concern is through CYP 3A4 inhibition with various ART meds Lovastatin and simvastatin are contraindicated Atorvastatin can be administered with monitoring Pitavastatin and rosuvastatin are probably safest Choice of and dosing depends on ASCVD risk  Cured Patients Two male patients are thought to be cured of HIV “Berlin” – Timothy Ray Brown Passed away September 2020 from recurrent leukemia “London” - Adam Castillejo Still considered “cured” as of Feb 2023 Both patients had blood cancers, received high dose chemo/XRT to kill their bone marrow and cancer cells, then received stem cell transplants from donors who carried a mutated CCR5 allele Other patients reported “Dusseldorf” – Marc Franke “New York” – first female case, reported Feb 2022, off ART for 14 months after haplo-cord transplant “City of Hope” – Paul Edmonds, received stem-cell transplant for leukemia, as of April 2023 off ART for 2 years “Geneva” – no viral rebound 54 months after transplant and ART Several reports of cured children over past few years, unable to find updates https://www.cnn.com/2019/03/04/health/hiv-remission-london-patient-study-bn/index.html Accessed Mar 10 2019 https://www.aidsmap.com/news/mar-2020/child-hiv-maintains-viral-suppression-three-years-treatment Accessed Nov 10th, 2021 https://www.medscape.com/viewarticle/968609#vp_1 Accessed Nov 9th, 2022 https://www.amfar.org/news/confirmed-dusseldorf-patient-cured-of-hiv/ Accessed Nov 10th, 2023 https://www.aidsmap.com/about-hiv/cases-hiv-cure Accessed Nov 10th, 2023 Case The patient is a 37-year-old male who presented to his PCP and requested HIV testing. His HIV antibody tests were positive, and he was referred to the ID clinic for treatment. His PMH is significant only for hypothyroidism, for which he takes levothyroxine 100mcg daily. His CBC and CMP values are within normal limits. His VL is 10,000 copies/mL and his CD4 count is 400 cells/mm3. Serologies for sexually transmitted co-infections are pending. His HLA-B*5701 test is positive. The viral tropism assay reveals that it is an X4 virus. Resistance testing results are pending. His BMP and CBC are within normal limits. What therapies should be started for RB? HIV Treatment Begin treatment as soon as diagnosis is confirmed! START trial: Multicontinental trial n = 4685 HIV positive adults, treatment naïve, CD4 > 500 Randomized to Immediate ART n = 2326 Deferred ART n = 2359 Primary outcomes Any serious AIDS related event; death from AIDS or any AIDS defining event, Hodgkin’s Any serious non-AIDS related event; CVD or death from CVD, end stage renal disease or death from renal disease, liver disease or death from liver disease, non-AIDS defining cancer (except for skin cancers) or death from cancer, any death not attributable to AIDS Initial Regimens Use co-formulated products whenever possible Constantly evolving process  Initial Regimens Preferred options If no history of using CAB-LA (Cabotegravir) as PrEP: Dual therapy (2 drug combo) – One drug has to be INSTI DTG/3TC (Dovato) – Dolutegravir and Lamivudine Indicated for treatment naïve patients Non-inferior to DTG/TDF/FTC at 48 and 96 weeks Don’t use for patients who: Pre-treatment HIV viral load > 500,000 copies/mL Have active Hepatitis B coinfection – NO monotherapy of Lamividine Will initiate therapy before results of genotype testing or hepatitis B testing available Concern for lower treatment response/treatment failure in patients with CD4 count 90 mL/min Assess CrCl every 12 months FTC/TAF As above Assess lipid panel for cholesterol and triglyceride levels and document weight https://www.cdc.gov/hiv/clinicians/prevention/prep.html Accessed Jan 28th, 2022 PrEP Counselling Assess indications and risk (see CDC guidelines) Screen for other STIs HIV acquisition is possible but rare Likely resistant HIV strain or high VL Well tolerated, safe in pregnancy Watch SCr and bone density PWID Very high risk PrEP should be offered along with treatment for SUD(s) Alcohol Use Loss of inhibition and/or impaired judgement https://www.preventionaccess.org/undetectable?lightbox=dataItem-j0iayi9y3 https://www.niaid.nih.gov/news-events/10-things-know-about-hiv-suppression Science Behind PrEP iPrEX Phase III international double-blind placebo controlled trial MSM and heterosexual couples 44% reduction in HIV acquisition (CI 15%-63%; p=0.005) N Engl J Med 2010;363:2587-99 iPrEX Adherence is crucial! For patients who completed the study and for whom detectible ART levels were found, RRR = 92% (CI 40-99; p