Jason Cronin, MD
Epidemiology Testing Clinical Features Management
In 1981, 1 the first cases of AIDS were identified among gay men in the US. However, scientists later found evidence that the disease existed in the world as early as 1959. Evolved from simian immunodeficiency virus (SIV) The first documented case of HIV was traced back to 1959 using preserved blood samples, which were analyzed in 1998. Globally 35.3 million people living with HIV/AIDS, 25 million in sub-saharan Africa 2.3 million new infections/year 1.6 million deaths due to AIDS/year 1.2 million individuals in the U.S. living with HIV/AIDS 1. UNAIDS Report on the Global AIDS Epidemic. http://www.unaids.org/en/resources/documents2013
1981 -First cluster of homosexual men with pneumocystis and Kaposi s sarcoma 1983 Identification of retrovirus eventually known as HIV 1985 - First serologic test for HIV-1 1987 zidovudine (AZT) approved 1996 First combination regimen (AZT, lamivudine, indinavir) N Engl J Med 1997; 337:734-739
9307 1981-2012 5581 Living 64 % MSM, 10% IDU 274 New cases/year last 15 years Increased rates 20-24 year olds since 2006 Counties with Highest Number People Living with HIV/AIDS County Number Multnomah 3076 Washington 569 Marion 372 Clackamas 357 Lane 301 Jackson 161 Deschuttes 91 Linn 63 Douglas 62 Epidemiologic Profile of HIV/AIDS in Oregon, public.health.oregon.gov/diseasesconditions/communicabled isease/diseasesurveillancedata/hivdat Josephine 58
Modes of transmission Sexual IVDA Transfusions (pre-1985, post-1985 1/1-2 million) Maternal-fetal transmission Occupational
Note: For comparison with data for 1999 and later years, data for 1987 1998 were modified to account for ICD-10 rules instead of ICD-9 rules.
Continuous ART arms of SMART and ESPRIT trials Non-IDU aged 2-70 T cells >350, VL undetectable or very low No increase in mortality for subgroup with T cells >500 compared with control 47 Causes of Death 3 31 19 Cardiovascular Disease Non-AIDS Malignancy AIDS-related Other AIDS 2013, 27:973 979
CDC Prior Recommendations: Targeted testing based on risk factors ER screening studies found as many as 43% of positive tests were in individuals with no traditional risk factors Reduced transmission and long-term morbidity due to earlier diagnosis Cost-effective even with relatively lowprevalence rates (1/1000)
Routine, voluntary testing for all persons 13-64 (Some groups recommend 75) at all points of care Annual repeat testing for individuals in higher risk groups (such as high risk sexual behavior, IVDU) Opt-out screening with opportunity to answer questions and decline No specific informed consent recommended
HIV antibody ELISA Rapid tests Western blot Combined antibody-antigen HIV Viral RNA
Types of HIV tests HIV Test 4 th Generation Laboratory Tests Architect HIV Ag/Ab Combo 6.2 (3.5, 8.5) GS HIV Combo Ag/Ab EIA 7.4 (3.8, 11.0) 3 rd Generation Laboratory Tests ADVIA Centaur HIV 1/O/2 9.9 (7.7, 12.0) Vitros anti-hiv 1+2 10.6 (8.7, 12.1) GS HIV-1/HIV-2 Plus O EIA 13.7 (11.3, 16.1) Number of days test positive after RNA detectable Median (95% CL) 3 rd Generation Rapid Test UniGold Recombigen HIV 21.6 (17.5, 27.8) 2 nd Generation Rapid Tests INSTI HIV-1 Antibody 13.5 (11.3, 14.8) Multispot HIV-1/2 16.8 (14.5, 18.9) DDP HIV-1/2 17.5 (14.0, 21.5) Reveal G2 HIV-1 19.0 (16.5, 20.0) Clearview Complete HIV-1/2 19.7 (17.5, 23.4) Clearview HIV-1/2 STATPAK 20.3 (17.4, 25.4) Oraquick Advance HIV-1/2 23.7 (18.2, 29.9) Class Interval 4 th -Generation Laboratory Tests 6.8 (3.7, 9.7) 3 rd -Generation Laboratory Tests 11.4 (9.7, 13.4) 2 nd -Generation Rapid Tests 18.5 (16.0, 21.6) Western Blot Laboratory Test 24.3 (18.8, 31.0)
OraQuick In-Home HIV Test
Symptoms Primary Clinical Latency Long-Term Nonprogressors (4-7%, At least 10 years CD4>500) Elite Controllers (Absent or very low viremia, 1/300 patients) HIV-associated symptoms AIDS Indicator Conditions Other Comorbidities
Viral load CD4 count Genetic Background Long-Term Nonprogressors (4-7%, At least 10 years CD4>500) Elite Controllers (Absent or very low viremia, 1/300 patients)
Incubation 2-4 weeks Fever Axillary, occipital, cervical lymphadenopathy Sore throat, shallow mucosal ulceration Maculopapular rash Lymphopenia, abnormal LFT s common HIV antibody negative, viral load very high
Thrush Persistent vaginal candidiasis Oral hairy leukoplakia Herpes zoster involving two episodes or multidermatomal Peripheral neuropathy Bacillary angiomatosis Cervical dysplasia Cervical carcinoma in situ Constitutional symptoms (fever or diarrhea >1 mo) Idiopathic thrombocytopenic purpura Pelvic inflammatory disease Listeriosis
CD4>200 Bacterial infections, multiple or recurrent* Cervical cancer, invasive Kaposi sarcoma Lymphoma, Burkitt (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Pneumonia, recurrent CD4<200 Candidiasis of bronchi, trachea, or lungs Candidiasis of esophagus Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Encephalopathy, HIV related Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex* Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month) Histoplasmosis, disseminated or extrapulmonary Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary Pneumocystis jirovecii pneumonia Wasting syndrome attributed to HIV Salmonella septicemia, recurrent Toxoplasmosis of brain, onset at age >1 month Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary CD4<50 Cryptosporidiosis, chronic intestinal (>1 month's duration) Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month Cytomegalovirus retinitis (with loss of vision) Isosporiasis, chronic intestinal (>1 month's duration) Lymphoma, primary, of brain Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Progressive multifocal leukoencephalopathy
4% 2% 2% 2% 2% 1% 1% 3% 3% 4% 5% 5% 11% 42% Pneumocystis Esophageal Candidiasis Wasting Kaposi's Disseminated M. avium Tuberculosis CMV Dementia Recurrent pneumonia Toxoplasmosis Immunoblastic lymphoma Cryptosporidiosis 11% 15% Burkitt's lymphoma Disseminated histoplasmosis Invasive cervical cancer Chronic herpes simplex
Malignancies Cardiovascular Coinfections Complex Pathogenesis Immune factors Behavioral factors Medication toxicity
Condition Non-AIDS Defining Malignancies Approximate risk Notes Hodgkin s Lymphoma 15 to 30x Increased unfavorable histology and advanced disease Plasma Cell Disorders 4.5x 2.5% MGUS Younger Age Hepatocellular 3.8x Coinfection with hepatitis C/B Lung cancer 2-4x More likely metastatic, less tobacco exposure Anogenital HPV Head and Neck 2-3x Younger Esophagus/Stomach 1.4,1.69x Cardiovascular Total 6.76 men, 2.47 women Both effect of HAART as well as direct effects on endothelium Controlled for other factors Diabetes 1.26 3x for HIV men on HAART Protease Inhibitors NRTI s
1996 all with CD4+ <500 or CD4 >500 and VL >30,000 1997 initiate if VL >10,000 copies/ml 2000 CD4+ <350, or VL >30,000, or CD4 350-500 and VL 5k-30k 2002 CD4 <200, otherwise clinical judtgment 2003 CD4 <200, offer if 200-350, clinical judgment >350 and VL >55,000 2004 <200, offer 200-350, most defer >350 and VL > 100k 2008 CD4 <350, otherwise consider 2009 CD4 <500, otherwise consider
More effective regimens More convenient regimens Better tolerated therapy Less long-term toxicity Better immune recovery Lower rates of resistance More treatment options Concerns for uncontrolled viremia Decrease HIV transmission Lack of RCT data supporting early Rx Potential drug toxicity Drug and monitoring cost Potential negative impact on QOL
Everyone, regardless of CD4 count Urgency of starting may depend on other factors such as patient readiness, presence of AIDS or AIDS-related comorbidities, pregnancy 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
NRTI Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir (TDF) Zidovudine (AZT, ZDV) 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 (II) Dolutegravir (DTG) Elvitegravir* (EVG) Raltegravir (RAL) Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) * EVG currently available only in coformulation with cobicistat (COBI)/ TDF/FTC May 2014 www.aidsetc.org 32
NNRTI-Based Regimen EFV/TDF/FTC 1 (AI) PI-Based Regimens (in alphabetical order) ATV/r + TDF/FTC 1 (AI) DRV/r (once daily) + TDF/FTC1 (AI) INSTI-Based Regimen DTG plus ABC/3TC (AI) only for patients who are HLA-B*5701 negative DTG plus TDF/FTC (A1) EVG/cobi/TDF/FTC only for patients with pre-art CrCl>70 ml/min (A1) RAL plus TDF/FTC (A1) In addition to above, following regimens recommended only for patients with pre-art plasma HIV RNA <100,000 copies/ml NNRTI-Based Regimen EFV plus ABC/3TC (A1) only for patients who are HLA-B*5701 negative RPV/TDF/FTC onlyfor patients with CD4 count >200 PI-Based Regimens (in alphabetical order) ATV/r plus ABC/3TC Panel on Antiretroviral (A1) only Guidelines for patients for Adults and who Adolescents. are HLA-B*5701 Guidelines for the negative 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
Fusion inhibitors Protease inhibitors Entry inhibitors Integrase inhibitors NRTI s NNRTI s
Condition NRTI s NNRTI s PI s Integrase Inhibitors Dyslipidemia D4T, AZT, ABC EFV All, ATV, DRV are less EVG/cobi/TD F/FTC Nephrotoxicity TDF EVG/cobi/TD F/FTC Insulin Resistance D4T, AZT, DDI IDV, LPV-rit Cardiovascular ABC, DDI Older PI s, limited data on ATV, DRV Lactic Acidosis Toxicity of Antiretrovirals D4T, AZT, DDI Lipodysrophy D4T, AZT??? Decreased bone density TDF Neuropsychiatr ic D4T/DDI/AZ T PN EFV depression, insomnia, vivid dreams Insomnia
Medical comorbidities AIDS-associated Non-AIDS associated Coinfections (hepatitis C, hepatitis B, Other STD s) Substance dependence and abuse, including tobacco Psychosocial Mental health Relational strain due to diagnosis Economic
Multidisciplinary Approach HIV Provider Case Management HIV-trained pharmacist Primary Care Provider Patient Mental Health Provider Other Specialty Care Family/Social support network Addiction Recovery
Little change in new cases despite current preventative measures AND increased in some subgroups Large scale trials in multiple populations showing benefit without emergence of resistance Now recommended by CDC for certain higher risk groups as one preventative option
Study Drug Population Results Notes Pre-exposure Prophylaxis Initiative (iprex) TDF-FTC Partners-PrEP TDF TDF-FTC 2499 HIVseronegative MSM 4758 discordant heterosexual couples in Africa TDF2 TDF-FTC 1200 heterosexual women TDF-FTC 2413 IVDU Thailand 100 infected, (36 I, 64 placebo) TDF-3TC with 75% reduced risk 62% reduced risk 50 infected (17 intervention, 33 placebo), 49% reduction Drug detected in only 9% of treatment arm Lancet. 2013 June;381 (9883):2083-90 N. Engl J Med. 2010;363(27):2587 N Engl J Med. 2012;367(5):399
MSM: Non-monogamous sexual activity past 6 months involving unprotected anal intercourse or recent bacterial STI Heterosexual: Infrequent condom use with partners of unknown HIV status expected high risk for HIV, recent bacterial STI Discordant couples where infected partner not well-controlled Active IV drug users with history sharing needles Preexposure Prophylaxis for the Prevention of HIV Infection in the United States 2014 Clinical Practice Guideline