HIV Medication Overview John J HIV Medication Overview John J. Faragon, PharmD, BCPS, AAHIV-P Albany Medical Center Hospital NY/NJ AIDS Education and Training Center

When to Start

DHHS: Changing Criteria for Initiating ART CD4+ Count, cells/mm3 1998 2001 2006 2008 2009 2012-2014 > 500 Offer if VL > 20,000 Offer if VL > 55,000 Consider if VL ≥ 100,000 Consider in certain groups Consider Treat 350-500 Consider if VL > 55,000 200-350 Offer, but controversy exists Offer after discussion with patient < 200 or symptomatic disease ART, antiretroviral therapy; DHHS, Department of Health and Human Services; VL, viral load. An overview of the DHHS guidelines over time highlights the evolution in both our understanding of the natural history of HIV and the advances in HIV therapy. Generally, there has been a movement toward recommending antiretroviral therapy for broader populations of patients over time. Looking specifically at patients with high CD4+ cell counts (> 500 cells/mm3), one sees that the threshold for considering initiation of antiretroviral therapy increased from 1998-2006, reflecting an increasing recognition of the long-term toxicities associated with the available regimens. However, more recent data indicate that there are benefits to starting antiretroviral therapy at high CD4+ cell counts both for maintaining strong immune function and reducing the likelihood of treatment-related adverse events. Moreover, the introduction of less toxic antiretroviral agents has somewhat diminished that concern. These factors have led to the movement toward treating nearly all patients, including those with higher CD4+ cell counts.   At the other end of the spectrum, antiretroviral therapy has always been recommended for patients with low CD4+ cell counts or, notably, those with symptomatic disease. Thus, even before the recommendation to initiate antiretroviral therapy regardless of CD4+ cell count, a patient with a high CD4+ cell count would still be recommended to start antiretroviral therapy on the basis of even subtle HIV-related symptoms, which could include chronic fatigue, night sweats, diarrhea, weight loss, or others.

Current Guidelines for Initiating ART – Other Guidelines Symptomatic/ AIDS CD4+ Count < 200 CD4+ Count 200-350 CD4+ Count 350-500 CD4+ Count > 500 DHHS (5/2014) Yes IAS-USA (7/2012) British HIV Association (9/2012) Defer* European AIDS Clinical Society (11/2012) Consider Defer WHO (7/2010) No† Not addressed ART, antiretroviral therapy; DHHS, Department of Health and Human Services; IAS-USA, International Antiviral Society-USA; WHO, World Health Organization. Other organizations have also recently updated their guidelines on when to start antiretroviral therapy. The International Antiviral Society (IAS)-USA guidelines, updated in 2012, also recommend initiating antiretroviral therapy regardless of CD4+ cell count.[1] European guidelines still do not actively recommend treatment at CD4+ cell counts > 350 cells/mm3,[2,3] although the British HIV Association does recognize the case for treating patients with high CD4+ cell counts to reduce the risk of transmission.[2] The World Health Organization guidelines are more conservative, as they must account for the limited resources that exist in many areas with a high prevalence of HIV.[4] In those areas, the primary focus remains on treating individuals with CD4+ cell counts < 350 cells/mm3. *If a patient with CD4+ count > 350 cells/mm³ wishes to start ART to reduce the risk of transmission to partners, that wish should be respected and ART started. †With the exception of an HIV-positive partner in a serodiscordant relationship, who should be offered antiretroviral therapy at CD4+ count > 350 cells/mm³ to prevent transmission to the uninfected partner.

Potential Benefits of Early Therapy: Supporting Data (2) CD4 count >500 cells/µL Cohort study data are not consistent; some show survival benefit if ART initiated early Other considerations (eg, potential benefit of ART on non-AIDS complications, HIV transmission risk) support recommendation for ART Data not entirely conclusive, especially for patients with very high CD4 counts… www.aidsetc.org

Why treat at CD4 >500 cells/mm3? Untreated HIV infection and ongoing viremia associated with development of non-AIDS defining diseases such as Cardiovascular Disease Renal disease Liver disease Neurologic complications Malignancy www.aidsetc.org

Community Viral Load Mirrors Reduced Rate of New HIV Cases in San Francisco Retrospective analysis of relationship between community viral load (CVL; mean of summed individual HIV-1 RNA results per yr) and new HIV diagnoses 30,000 P = .005 for association* Mean CVL 1200 Newly diagnosed and reported HIV cases 25,000 1000 20,000 800 Mean Community Viral Load (copies/mL) 798 Number of Newly Diagnosed HIV Cases 15,000 600 642 10,000 523 518 434 400 5000 200 2004 2005 2006 2007 2008 Yr *Data insufficient to prove significant association with reduced HIV incidence. Das-Douglas M, et al. CROI 2010. Abstract 33. Reproduced with permission.

http://insight.ccbr.umn.edu- START Protocol Synopsis START Study INSIGHT Network: multinational Study population: adults with CD4 >500 Study treatment: Immediate ART CD4 <350 Study endpoints: Serious AIDS-defining illness, non-AIDS illness, death Sample size: N=900 (pilot for feasibility; enrollment completed) N=3100 (definitive) Duration: ~6 yrs. http://insight.ccbr.umn.edu- START Protocol Synopsis

What to Start

Current ARV Medications NRTI Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir (TDF) Zidovudine (AZT) NNRTI Delavirdine (DLV) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV) Tipranavir (TPV) Integrase Inhibitor Raltegravir (RAL) Elvitegravir (EVG) Dolutegravir (DTG) Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) 26 medications, but we use only about ½ of them usually www.aidsetc.org

3-Drug Combination ART 1996: Crixivan/Retrovir/Epivir 8AM 4PM 12 MID Fasting (1 hour before/2 hours after meals)1.5 liters of hydration/day

HIV Lifecycle And Drug Targets Fusion Entry Inhibitors Nukes and Non Nukes Budding Reverse transcription Uncoating Viral DNA Assembly 3’-processing Pre-Integration Complex Viral proteins Integrase Inhibitors Protein chains Viral RNA Integration (strand transfer) Nucleus Translation Transcription Human Genomic DNA Viral DNA RNA Protease Inhibitors

DHHS Guidelines Update 2014: Recommended Regimens in ARV Naives Regardless of Baseline CD4 and Viral Load NNRTI – Based Regimen Efavirenz/tenofovir/emtricitabine (AI) PI – Based Regimens: Atazanavir/ritonavir + tenofovir/emtrictiabine (AI) Darunavir/ritonavir + tenofovir/emtricitabine (AI) INSTI – Based Regimens: Dolutegravir plus abacavir/lamivudine – ONLY if patient HLA-B*5701 negative (AI) Dolutegravir plus tenofovir/emtricitabine (AI) Elvitegravir/cobicistat/tenofovir/emtricitabine – ONLY if pre-ART CrCl >70ml/min (AI) Raltegravir plus tenofovir/emtricitabine (AI) May 2014 updated regimens and removed the previous designation of preferred regimens and now call them “recommended” regimens, and are classified as NNRTI, boosted PI, or INSTI based. In general regimens recommended consist of 2 NRTIs and one of the 3 other classes in addition. Read regimens above and include caveats Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14

DHHS Guidelines Initial Recommended Regimens - 2014 Atripla 1/day Reyataz/Norvir/Truvada 3/day This slide provides the pill burden of preferred regimens and pictures of what the pills actually look like Prezista/Norvir/Truvada 3/day Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14.

DHHS Guidelines Initial Recommended Regimens - 2014 Isentress (BID)/Truvada 3/day Tivicay/Truvada OR Epzicom 2/day OR This slide provides the pill burden of preferred regimens and pictures of what the pills actually look like Stribild 1/day Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14.

Atripla Key Points 3 drugs in one tablet Efavirenz/tenofovir/emtricitabine AKA Sustiva+Truvada Dosed at bedtime usually Pregnancy Category D CNS side effects common in first few weeks Renal side effects possible with tenofovir

Reyataz Norvir Truvada Key Points 3 pills daily “Boosted” PI regimen Dosed once a day with food GI side effects, minimal effect on lipids Hyperbilirubinemia, nephrolithiasis Proton Pump Inhibitor interaction Renal side effects possible with tenofovir

Prezista Norvir Truvada Key Points 3 tablets daily “Boosted” PI regimen Dosed once a day with food GI side effects, minimal effect on lipids Sulfa moeity Renal side effects possible with tenofovir 400mg off market now!

Ritonavir (Norvir®, RTV, r) Dosing / Administration For PI-boosting: 100-200mg PO BID or daily Full dose - 600mg PO Q12H (usually wrong) Take with food to improve tolerability Refrigerate capsules Adverse effects GI effects, taste perversion, circumoral tingling  [cholesterol] &  [triglycerides] Drug interactions Potent CYP3A4 inhibitor and inducer

Single-Dose Pharmacokinetics of Lopinavir With and Without Ritonavir Lopinavir/ritonavir Lopinavir Concentration (mg/mL) While Kaletra is the only co-formulated boosted PI, most PI’s are today using RTV-enhancement to significantly improve drug concentrations. One difference that may be important, is that not only is lopinavir uniquely susceptible to boosting, but it also could not be used as a sole PI. As you can see, without boosting, this is a drug that would not have likely come to market due to poor PK. However with RTV, it’s concentration are about 70-fold the IC50 for WT virus IC50 wt HIV Lopinavir alone 0 6 12 18 24 30 36 42 48 Time After Dosing (hr) Sham HL, et al. Antimicrob Agents Chemother. 1998;42(12):3218-3224; Lal R, et al., 37th ICAAC, 1997, # I-194

Why Norvir Boosted Protease Inhibitors Less resistance – nearly no resistance reported in naïve trials with all boosted PI regimens currently on guidelines Lower pill burdens Reduced frequency – now all are once daily, versus 2-3 times daily for unboosted protease inhibitors “Ritonaphobia” is the REAL downside

Isentress Truvada Key Points 3 tablets Isentress dosed twice a day Once daily dosing possible, but inferior to BID Well tolerated, no effect on lipids Renal side effects possible with tenofovir

Stribild Key Points 4 drugs in one tablet Elvitegravir – a new integrase inhibitor Cobicistat – a new booster (does the same thing as RTV) Tenofovir – preferred NRTI Emtricitiabine – preferred NRTI Head to head data with Atripla and Reyataz/Norvir/Truvada showed similar results (non- inferior at 48 weeks) Sax P, et al. CROI 2012. Abstract 101. DeJesus E, et al. CROI 2012. Abstract 627.

Stribild – Additional Information Contains cobicistat Booster for the elvitegravir Similar to Norvir for drug interactions Increased creatinine levels due to inhibition of tubular secretion of creatinine back into bloodstream in the kidney Similar to cimetidine

X Tubular Reabsorption Substances reabsorbed back into blood from the renal tubule Tubular Secretion Substances secreted from the blood back into renal tubule for elimination Blocking Tubular Secretion Cobicistat BLOCKS tubular secretion of creatinine, causing an increase in blood levels of creatinine X

Tivicay Key Points OR FDA-approved August 12, 2013 Approved for wide range of HIV populations, adults and children aged 12 and above and at least 40kg New integrase inhibitor dosed as a 50 mg tablet Once daily for treatment-naïve patients Twice daily for integrase treatment-experienced patients Can be taken with or without food Pregnancy category B Adverse events > 2% were insomnia and headache Contra-indicated to be given with dofetilide, an anti-arrhythmic Submitted to FDA STR of Epzicom/dolutegravir

Tivicay Dosing Treatment naïve or treatment experienced, integrase inhibitor naïve 50mg once daily Treatment naïve or treatment experienced, with UGT1A/CYP3A4 inducers: Efavirenz, fosamprenavir/ritonavir, tipranavir, or rifampin 50mg twice daily Integrase inhibitor with II resistance No food restrictions Separate from cations – ie Magnesium, Calcium, Iron

DHHS Guidelines Update 2014: Recommended Regimens, ARV Naives, ONLY if Pre ART Viral Load <100,000 copies/ml NNRTI – Based Regimen Efavirenz + abacavir/lamivudine – ONLY if patient HLA-B*5701 negative (AI) Rilpivirine/tenofovir/emtricitabine – ONLY if patient has CD4 count>200 cells/mm3 (AI) PI – Based Regimens: Atazanavir/ritonavir + abacavir/lamivudine (AI) – ONLY if patient is HLA-B*5701 negative The regimens listed here are also from the 2014 DHHS Guidelines and are the recommended regimens, but only if viral loads are less than 100,000 copies/ml at baseline. In this class there are 2 NNRTI based regimens, and one PI based option. Of concern here is that some regimens do not perform as well in patients with higher viral loads so the viral load cutoff designation is important to recognize with these regimens. Read regimens above with caveats Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14

Complera Rilpivirine/tenofovir/emtricitabine STR once daily Food required Take antacids at least 2 hours before or at least 4 hours after Take H-2 blockers at least 12 hours before or at least 4 hours after PPIs are contraindicated

DHHS Guidelines Update 2014 Alternative Regimens in ARV Naives PI – Based Regimen Darunavir/ritonavir + abacavir/lamivudine – ONLY for patients who are HLA-B*5701 negative (BII) Lopinavir/ritonavir (once or twice daily) plus abacavir/lamivudine – ONLY for patients who are HLA-B*5701 negative (BI) Lopinavir/ritonavir (once or twice daily) plus tenofovir/emtricitabine (BI) INSTI – Based Regimens: Raltegravir + abacavir/lamivudine – ONLY for patients who are HLA-B*5701 negative The following regimens are listed on DHHS as Alternative regimens and should be used if patients can not use or tolerate a recommended regimen. Read regimens on slide Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14

Preferred NRTI Backbones in Pregnancy – DHHS Perinatal Guidelines, March 2014 Abacavir/lamivudine Available as fixed dose combination, once daily dosing. Do NOT use in patients testing positive for HLAB*5701 Tenofovir/emtricitabine or lamivudine Available as fixed dose combination, once daily dosing. Tenofovir may cause renal impairment Zidovudine/lamivudine Available as fixed dose combination. Most experience in pregnancy to date, but twice daily adminstration, and potential for hematologic toxicity In this slide, I have summarized in table format the changes to the DHHS guidelines. READ CHART with caveats on right side. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed 5/2/14

Preferred PI, NNRTI Regimens in Pregnancy – DHHS Perinatal Guidelines, March 2014 Preferred PI Regimens Atazanavir/ritonavir + preferred dual NRTI backbone Once daily administration Lopinavir/ritonavir + preferred dual NRTI backbone Twice daily administration. Once daily dosing not recommended in pregnancy. May need to increase dosage in 3rd trimester Preferred NNRTI Regimens Efavirenz + preferred dual NRTI backbone initiated AFTER first 8 weeks of pregnancy Teratogenicity in primates. Preferred PI and NNRTI regimens in Pregnancy are also listed here and include comments/cavetas. Read Slidewith caveats on right Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed 5/2/14

What to Avoid

ARV Medications: Should NOT Be Offered at ANY Time ARV regimens not recommended: Monotherapy with NRTI* Monotherapy with boosted PI Dual-NRTI therapy 3-NRTI regimen (except ABC + 3TC + ZDV or possibly TDF + 3TC + ZDV) * ZDV monotherapy is not recommended for prevention of perinatal HIV transmission but might be considered in certain circumstances; see Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. www.aidsetc.org

ARV Medications: Should NOT Be Offered at ANY Time ARV components not recommended: Didanosine + stavudine Didanosine + tenofovir Emtricitabine + lamivudine Stavudine + zidovudine Darunavir, saquinavir, or tipranavir as single, unboosted PIs Atazanavir + Indinavir www.aidsetc.org

ARV Medications: Should NOT Be Offered at ANY Time ARV components not recommended: Efavirenz during first trimester of pregnancy and in women with significant potential for pregnancy Nevirapine initiation in women with CD4 counts of >250 cells/µL or in men with CD4 counts of >400 cells/µL Etravirine + unboosted PI Etravirine + boosted Atazanavir, fosamprenavir or tipranavir Any combination of 2 NNRTIs www.aidsetc.org

PrEP Guidelines

2014 CDC PrEP Guidelines Guidelines for PrEP were released in May 2014 Addresses the role of PrEP in the following adult populations Men who have sex with men Heterosexual men and woman Injection Drug Users Sero-discordant couples ONLY medication to be used in this setting is tenofovir/emtricitabine (Turvada) In May 2014, the CDC released final guidelines on PrEP in the US. Prior to this there were only interim guidance in select populations. This guidelines discusses the role of PrEP in men who have sex with men, heterosexual men and woman, injection Drug Users and in sero-discordant couples http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

Results of PrEP Trials, CDC Results from randomized, placebo-controlled, clinical trials of the efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for preventing human immunodeficiency virus (HIV) infection Clinical trial Participants Type of medication mITT efficacy* Adherence-adjusted efficacy based on TDF detection in blood % (95% CI) Bangkok Tenofovir Study Injecting drug users TDF 49 (10–72) 70 (2–91) Partners PrEP HIV discordant couples 67 (44–81) 86 (67–94) TDF/FTC 75 (55–87) 90 (58–98) TDF2 Heterosexually active men and women 62 (22–83) 84 NS iPrEx Men who have sex with men 42 (18–60) 92 (40–99) Fem-PrEP Heterosexually active women — NA VOICE Abbreviations: mITT = modified intent to treat analysis, excluding persons determined to have had HIV infection at enrollment; CI = confidence interval; TDF = tenofovir disoproxil fumarate; FTC = emtricitabine; NS = not statistically significant; NA = data not available. * % reduction in acquisition of HIV infection. This is a nice summary slide of all results of the PrEP studies in various populations for your review. Center for Disease Control. MMWR. June 14, 2013 / 62(23);463-465

2014 CDC PrEP Guidelines – Recommended Indications for PrEP Use in MSM Adult man Without acute or established HIV infection Any male sex partners in past 6 months Not in a monogamous partnership with a recently tested, HIV-negative man AND at least one of the following Any anal sex without condoms (receptive or insertive) in past 6 months Any STI diagnosed or reported in past 6 months Is in an ongoing sexual relationship with an HIV-positive male partner An for indication for PrEP for MSM the guidelines recommend daily PrEP for MSM who are: An Adult man Without acute or established HIV infection Any male sex partners in past 6 months Not in a monogamous partnership with a recently tested, HIV-negative man AND at least one of the following Any anal sex without condoms (receptive or insertive) in past 6 months Any STI diagnosed or reported in past 6 months Is in an ongoing sexual relationship with an HIV-positive male partner http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

2014 CDC PrEP Guidelines – Recommended Indications for PrEP Use in Heterosexual Men and Women Adult person Without acute or established HIV infection Any sex with opposite sex partners in past 6 months Not in a monogamous partnership with a recently tested HIV-negative partner AND at least one of the following Is a man who has sex with both women and men (behaviorally bisexual) Infrequently uses condoms during sex with 1 or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (IDU or bisexual male partner) Is in an ongoing sexual relationship with an HIV-positive partner As for indications for PrEP in heterosexual men and women, the guidelines recommend daily Truvada for those who are: Adult person Without acute or established HIV infection Any sex with opposite sex partners in past 6 months Not in a monogamous partnership with a recently tested HIV-negative partner AND at least one of the following Is a man who has sex with both women and men (behaviorally bisexual) Infrequently uses condoms during sex with 1 or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (IDU or bisexual male partner) Is in an ongoing sexual relationship with an HIV-positive partner http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

2014 CDC PrEP Guidelines – Recommended Indications for PrEP Use Injection Drug Users Adult person Without acute or established HIV infection Any injection of drugs not prescribed by a clinician in past 6 months AND at least one of the following Any sharing of injection or drug preparation equipment in past 6 months Been in a methadone, buprenorphine, or suboxone treatment program in past 6 months Risk of sexual acquisition And for indications, the CDC recommends the following in IVDUs: Adult person Without acute or established HIV infection Any injection of drugs not prescribed by a clinician in past 6 months AND at least one of the following Any sharing of injection or drug preparation equipment in past 6 months Been in a methadone, buprenorphine, or suboxone treatment program in past 6 months Risk of sexual acquisition http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

2014 CDC PrEP Guidelines – Monitoring All patients receiving PrEP should be seen as follows: At least every 3 months to Repeat HIV testing and assess for signs or symptoms of acute infection to document that patients are still HIV negative Repeat pregnancy testing for women who may become pregnant Provide a prescription or refill authorization of daily TDF/FTC for no more than 90 days (until the next HIV test) Assess side effects, adherence, and HIV acquisition risk behaviors Provide support for medication adherence and risk-reduction behaviors Respond to new questions and provide any new information about PrEP use As for monitoring, patients on PREP should be seen every 3 months to Repeat HIV testing and assess for signs or symptoms of acute infection to document that patients are still HIV negative Repeat pregnancy testing for women who may become pregnant Provide a prescription or refill authorization of daily TDF/FTC for no more than 90 days (until the next HIV test) Assess side effects, adherence, and HIV acquisition risk behaviors Provide support for medication adherence and risk-reduction behaviors Respond to new questions and provide any new information about PrEP use http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

2014 CDC PrEP Guidelines – Monitoring At least every 6 months to Monitor eCrCl If other threats to renal safety are present renal function may require more frequent monitoring or may need to include additional tests A rise in serum creatinine is not a reason to withhold treatment if eCrCl remains ≥60 ml/min. If eCrCl is declining steadily (but still ≥60 ml/min), consultation with a nephrologist may be indicated. Conduct STI testing recommended for sexually active adolescents and adults (i.e., syphilis, gonorrhea, chlamydia) At least every 12 months to Evaluate the need to continue PrEP as a component of HIV prevention Monitoring is also recommended at various intervals, In particular: At least every 6 months to Monitor eCrCl If other threats to renal safety are present renal function may require more frequent monitoring or may need to include additional tests A rise in serum creatinine is not a reason to withhold treatment if eCrCl remains ≥60 ml/min. If eCrCl is declining steadily (but still ≥60 ml/min), consultation with a nephrologist may be indicated. Conduct STI testing recommended for sexually active adolescents and adults (i.e., syphilis, gonorrhea, chlamydia) At least every 12 months to Evaluate the need to continue PrEP as a component of HIV prevention http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf. Accessed 5/15/14.

PEP Guidelines

HIV Prophylaxis Following Exposure The Medical Care Criteria Committee now recommends tenofovir + emtricitabine* plus raltegravir as the preferred initial PEP regimen excellent tolerability, proven potency, and ease of administration. Zidovudine is no longer recommended no clear advantage in efficacy over tenofovir higher rates of treatment-limiting side effects.

HIV Prophylaxis Following Occupational Exposure Recommendations place emphasis on the importance of initiating occupational PEP as soon as possible, ideally within 2 hours of exposure. First dose of PEP should be offered while evaluation is underway. PEP should not be delayed while awaiting source patient or results of the exposed baseline HIV test.

Updated Public Health Service Occupational PEP Guidelines, November 2013 Preferred HIV PEP Regimen Raltegravir (Isentress; RAL) 400 mg PO twice daily PLUS Truvada, 1 PO once daily (Tenofovir DF [Viread; TDF] 300 mg + emtricitabine [Emtriva; FTC] 200 mg) Fixed Dose Combination Guidelines for Occupational Exposure of HIV infection were recently updated form the 2 and 3 drug regimen in previous versions to a more simple regimen of Isentress and Truvada – This regimen is also on the NYS DOH guidelines and has been shown to have favorable tolerability. In addition, the approval of Truvada for PrEP also supports the use of this regimen. Finally, the fact that isentress works pre-transcritiptional in the life cycle of HIV supports its role in this setting. Kuhar DT. Infect Control Hosp Epidemiol. 2013;34(9):875-92.

Resources

Web Resources of Interest DHHS Guideline Tables http://www.aidsinfo.nih.gov/guidelines/ NY/NJ AIDS Education and Training Center http://www.nynjaetc.org/ University of Liverpool www.hiv-druginteractions.org Toronto HIV Clinic http://www.hivclinic.ca/main/home

http://aidsinfo.nih.gov/guidelines/

www.hiv-druginteractions.org

www.hiv-druginteractions.org Upper Left Corner New data, reports Top middle – Charts and Recommendations

www.hep-druginteractions.org Good reference

www.nynjaetc.org

www.nynjaetc.org CLICK HERE

www.nynjaetc.org CLICK HERE

NY/NJ AETC – www.nynjaetc.org

NY/NJ AETC – www.nynjaetc.org

NY/NJ AETC – www.nynjaetc.org

NY/NJ AETC – www.nynjaetc.org

www.hivguidelines.org

HIV Medication Overview John J HIV Medication Overview John J. Faragon, PharmD, BCPS, AAHIV-P Albany Medical Center Hospital NY/NJ AIDS Education and Training Center