1:30 2:30pm HIV Update SPEAKER Gordon Dickinson, MD Presenter Disclosure Information The following relationships exist related to this presentation: Gordon Dickinson, MD, has no financial relationships to disclose. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Objectives HIV in the Trenches HIV Update for the Primary Care Provider, 2015 Gordon Dickinson, MD Professor of Medicine, University of Miami Miller School of Medicine, and Chief, Infectious Diseases Section, Miami VA Medical Center 1. Appropriately screen patients for HIV infection. 2. Recognize signs and symptoms of acute retroviral syndrome. 3. Discuss factors that impact the selection of an antiretroviral regimen. 4. Describe when PrEP (pre-exposure prophylaxis) is indicated. Epidemiology Estimated persons worldwide infected with HIV since onset of epidemic 38 million Estimated numbers of persons living with HIV in the US 1.2 million Newly infected persons per year in USA ~50,000 An Overview The HIV Continuum of Care HIV infection HIV diagnosis In HIV specialty care HIV anti-retroviral therapy initiated HIV Fully suppressed Thus, all patients ideally move through the continuum from infection to successfully treated status.
Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings For patients in all health-care settings HIV screening recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening) Annual screening for persons at high risk for HIV infection General consent for medical care sufficient to encompass consent for HIV testing Prevention counseling not required with HIV diagnostic testing or as part of HIV screening programs in health-care settings For pregnant patients: Include HIV screening in the routine panel of prenatal screening tests for all pregnant women Opt-out screening General consent for medical care sufficient for HIV testing Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women MMWR September 22, 2006 / 55(RR14);1-17. MMWR September 22, 2006 / 55(RR14);1-17. To Summarize Screening for HIV: Acute Retroviral Syndrome 1. All pregnant women 2. All persons between 13 and 64 yrs of age on one occasion (unless known to be at < 1/1000 risk) 3. Patients initiating treatment for TB 4. Patients with an active STD 5. Repeat Screening Patients at risk Screen men who have sex with men Sex workers Persons who inject illicit drugs Sex partners of persons with HIV Persons who have sex with multiple partners A mononucleosis-like syndrome is common Specific symptoms & Signs in 209 patients (Niu, JID 1993): Fever 96% Lymphadenopathy 74% Rash 70% Pharyngitis 70% Myalgia or arthralgia 54% Thrombocytopenia 45% Diarrhea, Headache, Nausea 38-27% Initial Evaluation of the Newly Diagnosed HIV 1. Thorough history 2. Thorough physical examination 3. Initial laboratory assessment 1. HIV RNA PCR quantitative assay ( viral load ) 2. HIV resistance genotype 3. T-lymphocyte panel (T-cell subsets) 4. CBC, Comprehensive Metabolic Panel, Lipid profile, Urinalysis 5. STD assessment Syphilis serology, Chlamydia/N gonorrhea DNA probe 6. Viral hepatitis panel: Hepatitis A, Hepatitis B and Hepatitis C 7. Tuberculin skin test (or QuantiferonGold TB assay) Antiretroviral Regimens More than 26 drugs 5 mechanisms of action Six combinations of two to four drugs Demonstrable efficacy and durability for indefinite periods well, up to 18 years and counting
Mechanisms of Action of Antiretrovirals 1. Inhibition of entry 2. Inhibition of fusion 3. Inhibition of HIV reverse transcriptase 4. Inhibition of integration into host DNA 5. Inhibition of protease enzyme Principles of Antiretroviral Therapy 1. The patient must be adherent 2. As of February 2015, treatment must include three drugs 3. As of February 2015, treatment must be continued indefinitely Factors that Impact the Choice of an Antiretroviral Regimen 1. The resistance genotype 2. Renal function 3. Hepatic disease 4. Potential drug interactions And.the patient s wishes HHS Panel on Antiretroviral Guidelines for Adults and Adolescents 2014 An authoritative guide updated at least yearly Recommends antiretroviral regimens Information on adverse effects of each antiretroviral drug Information on drug interactions http://aidsinfo.nih.gov/guidelines Recommended Antiretroviral Regimens 2014 1. Efavirenz/tenofovir/emtricitabine (Atripla) 2. Atazanavir/ritonavir plus tenofovir/emtricitabine 3. Darunavir/ritonavir plus tenofovir/emtricitabine 4. Raltegravir plus Tenofovir/emtircitabine 5. Dolutegravir plus tenofovir/emtricitabine 6. Dolutegravir plus abacavir/lamivudine And if plasma HIV RNA is < 100,000 copies/ml 1. Efavirenz plus abacavir/lamivudine 2. Rilpivirine plus tenofovir/lamivudine Adverse Consequences of Anti-Retroviral Therapy Adverse consequences on the ART Rifampin decreases efavirenz levels Proton blockers decreases absorptions of Pis and NNRTIs Adverse consequences on other drugs Ritonavir enhances levels of amiodarone Enhanced toxicity for patient Statins and NNRTIs hepatitis http://aidsinfo.nih.gov/guidelines
Clinical Definition of Immune Reconstitution Syndrome in the Context of HIV Infection Infectious & Non-Infectious Etiologies of IRIS Required Criterion Worsoning symptoms of inflammation/infection Temporal relationship with starting antiretroviral treatment Symptoms not explained be newly acquired infection or disease or the usual course of a previously acquired disease 1 log 10 decrease in plasma HIV load Supportive Criterion Increase in CD4 + cell count of 25 cells/mm 3 Biopsy demonstrating wellformed granulomatous inflammation or unusually exuberant inflammatory response Infectious: Mycobacteria Cryptococcosis Cytomegalovirus Infection Hepatitis B, Hepatitis C Non-Infectious AIDS-related lymphoma Rheumatologic/Autoimmune diseases Robertson J et al. Clin Infect Dis. 2006;42:1639-1646. Murdoch et al. AIDS Res Ther. 2007;4:9. Pre-Exposure Prophylaxis (PREP) 1990 Post exposure recommendations for occupational exposures and updated periodically (last, September 2013) 1995 Prevention of vertical transmission to newborn is highly successful What about prevention for persons at risk? Kaplan-Meier Estimates of Time to HIV Infection (Modified Intention-to-Treat Population) Cumulative Probability of HIV Infection 1.0 0.8 0.6 0.4 0.2 0.0 No. at Risk Placebo FTC-TDF 0 P = 0.005 Placebo FTC-TDF 12 24 36 48 60 72 84 96 108 120 132 Weeks since Randomization 1248 1194 1108 1005 852 647 546 444 370 258 137 60 1251 1188 1097 988 848 693 558 447 367 267 147 65 Grant RM et al. N Engl J Med. 2010;363:2587-2599. PrEP Recommendations CDC, May 2014 Summary of Guidance for PrEP Use Detecting substantial risk of acquiring HIV infection Men Who Have Sex with Men Heterosexual Women and Men Injection Drug Users HIV-positive sexual partner Recent bacterial STI High number of sex partners History of inconsistent or no condom use Commercial sex work HIV-positive sexual partner Recent bacterial STI High number of sex partners History of inconsistent or no condom use Commercial sex work In high-prevalence area or network Documented negative HIV test result before prescribing PrEP Clinically No signs/symptoms of acute HIV infection eligible Normal renal function; no contraindicated medications Documented hepatitis B virus infection and vaccination status Prescription Daily, continuing, oral doses of TDF/FTC (Truvada), 90-day supply Other services HIV-positive injecting partner Sharing injection equipment Recent drug treatment (but currently injecting) Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment At 3 months and every 6 months thereafter, assess renal function Every 6 months, test for bacterial STIs Summary Pre-Exposure Prophylaxis (PrEP) Persons at high risk for HIV infection can be identified If taken daily, PrEP is highly effective Should be prescribed only in the context of ongoing supervision and periodic evaluations for HIV and other STDs Do oral/rectal STI testing Assess pregnancy intent Pregnancy test every 3 months Assess to clean needles/syringes and drug treatment services STI = sexually transmitted infection.
In Summary I In Summary II HIV is now endemic in the USA, with periodic testing indicated for subgroups at risk All age groups are at risk for infection Consider acute retroviral syndrome for acute febrile illnesses in sexually active adults HIV treatment: Initiate treatment at any level of CD4 count Combination or cocktail of drugs are successful indefinitely Drug interaction must always be considered PreExposure Prophylaxis (PrEP) indicated for all at high risk for infection