1 / 64

HIV Update

HIV Update. History. HIV was originally described in 1981 Cluster of cases of Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma (KS) in previously healthy males Previously very unusual infections in the U.S. PCP and KS. History. The virus was first identified in 1983

habib
Download Presentation

HIV Update

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HIV Update

  2. History • HIV was originally described in 1981 • Cluster of cases of Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma (KS) in previously healthy males • Previously very unusual infections in the U.S.

  3. PCP and KS

  4. History • The virus was first identified in 1983 • Luc Montagnier and Robert Gallo • The first blood test (ELISA) was developed in 1985 • Screening of blood supply initiated

  5. First HIV-1 Infections • Central Africa • First human case in 1959 • US: • Haitian connection (UNESCO program to Congo in the 1960s) • Airline steward helped disseminate HIV in the US and Europe • Worobey’s Study • Studied genetic relatedness of strains and hypothesized that first infection occurred in ~1908 • Although HIV may have existed for decades, epidemic began in the 1950s/1960s • Urbanization, prostitution, needle use, war, and travel/tourism

  6. HIV = Zoonosis • -Cross-species infections • Sooty Mangabey: HIV-2 • Chimpanzee: HIV-1 • -Transmission via exposure to blood, including for chimps (cuts, ingestion) • -Benign infection in Chimpanzees • 98% homology with HIV (?? which genes protective) • -Did chimps die off millions of years ago from SIV? Did NOT originate from: contaminated vaccines, biologic engineering/ weaponry; cats (feline leukemia virus), etc.

  7. Relationships Among Primate Lentiviruses B SIVSTM HIV-2 100 A 100 HIV-1 group O 100 SIVSM 100 100 100 G A CPZANT 100 CPZGB A/E 76 100 100 100 A/G 96 100 100 92 B HIV-1 group N 77 H 99 94 99 F D J C HIV-1 group M .10

  8. HIV-1 Subtypes

  9. HIV Virus Replication: 10 Billions copies/day

  10. HIV Replication

  11. A global view of HIV infection 33 million people [30–36 million] living with HIV, 2007

  12. Adults and children estimated to be living with HIV, 2007 Eastern Europe & Central Asia 1.5 million [1.1 – 1.9 million] Western & Central Europe 730 000 [580 000 – 1.0 million] North America 1.2 million [760 000 – 2.0 million] East Asia 740 000 [480 000 – 1.1 million] Middle East&North Africa 380 000 [280 000 – 510 000] Caribbean 230 000 [210 000 – 270 000] South & South-East Asia 4.2 million [3.5 – 5.3 million] Sub-Saharan Africa 22.0 million [20.5 – 23.6 million] Latin America 1.7 million [1.5 – 2.1 million] Oceania 74 000 [66 000 – 93 000] Total: 33 million (30 – 36 million)

  13. Over 7,400 new HIV infections a day in 2007 • More than 96% are in low and middle income countries • About 1,000 are in children under 15 years of age • About 6,300 are in adults aged 15 years and older • of whom: • almost 50% are among women • about 45% are among young people (15-24)

  14. 25 years of AIDS People living with HIV 50 1 First cases of unusual immune deficiency are identified among gay men in USA, and a new deadly disease noticed 9 In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease, the first major downturns in the epidemic in developing countries 45 Million 2 Acquired Immune Deficiency Syndrome (AIDS) is defined for the first time 40 3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS 10 Highly Active Antiretroviral Treatment launched 35 4 In Africa, a heterosexual AIDS epidemic is revealed 11 Scientists develop the first treatment regimen to reduce mother-to-child transmission of HIV 5 The first HIV antibody test becomes available 30 6 Global Network of People living with HIV/AIDS (GNP+) (then International Steering Committee of People Living with HIV/AIDS) founded 11 Children orphaned by AIDS in sub-Saharan Africa 12 UNAIDS is created 25 13 Brazil becomes the first developing country to provide antiretroviral therapy through its public health system 7 The World Health Organisation launches the Global Programme on AIDS 20 8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA 14 The UN General Assembly Special Session on HIV/AIDS. Global Fund to fight AIDS, Tuberculosis and Malaria launched 15 12 10 15 WHO and UNAIDS launch the "3 x 5" initiative with the goal of reaching 3 million people in developing world with ART by 2005 5 9 1 2 4 6 8 5 13 14 15 16 7 10 3 16 Global Coalition on Women and AIDS launched 0 2005 1980 1985 1990 1995 2000 1.1

  15. Reason for Falling Death Rates • Impact of HAART • Highly Active Anti-Retroviral Therapy • Defined as three or more ARV drugs • Protease inhibitors were approved for use in 1995 • Earlier recognition & treatment • Identifying HIV patients so they could be treated • Still an issue: approximately 250,000 undiagnosed cases in the U.S.! • Response: CDC recommends testing for all persons (regardless of risk factors) from ages 13 to 64 years • Annual testing for high-risk persons • OI prophylaxis, multi-discplinary HIV care, etc.

  16. Current Issues • Continued new infections despite knowledge of prevention • Lack of safe sex practices • High rate of STIs (e.g., syphilis) • False sense of security after HAART availability • Lack of ART availability for the entire world • Long term health effects of chronic HIV infection as well as long term ART use

  17. How HIV is transmitted • Unprotected Sex • Anal>vaginal>oral • Risk is most associated with Viral Load • Increased risk with bleeding or tearing of tissues • Higher risk in the receptive partner • Concurrent STI • Lack of circumcision • Sharing needles or IV drug use • Infected mother to her baby • While baby is developing in the womb • During the birthing process • From breastfeeding (30-40% risk in 6 months) • Blood transfusion (1:1 Million)

  18. How HIV is not transmitted • Coughing • Sneezing • Shaking hands • Casual kiss • Toilet seats • Bites from mosquitoes or fleas

  19. Transmission • The risk for transmission is highest during the first year after being infected • Viral load is highest during early infection (and in the late stages) • Unfortunately, most people do not know they are infected during this time

  20. Diagnosis • HIV ELISA • Usually positive within 3-4 weeks, rarely test can become positive up to 6 months after infection • Confirmatory Western Blot test • Indeterminate test due to advanced HIV, HIV-2, autoimmune disease, pregnancy • Overall, between the two tests it is very accurate • Polymerase Chain Reaction (PCR) • Positive earlier than ELISA • Used to test people when we suspect “Seroconverting Illness”

  21. Stages of HIV Infection • Viral transmission • Primary HIV infection (acute HIV infection or acute seroconversion syndrome) • Occurs in approximately 60% of cases • Seroconversion • ELISA becomes positive due to antibody production • Clinical latent period • Typically 8-10 years in duration • AIDS • End-Stage/Death

  22. Seroconverting Symptoms • Fever 87% • Rash 68% • Pharyngitis 48% • Myalgias 42% • Headache 39% • Diarrhea 32% • Abdominal Pain 32% • Arthralgias 29% • Nausea/Vomiting 29%

  23. Seroconverting Rash

  24. Natural History of HIV

  25. Genetics and Disease ProgressionScience; 313:462-6

  26. AIDS • Defined by CD4 count below 200 (<14%) or an AIDS-defining condition* • P. carinii/jiroveci pneumonia • Esophageal candidiasis • Wasting • Kaposi's sarcoma • Disseminated M. avium infection (MAC) • Tuberculosis • Cytomegalovirus disease • HIV-associated dementia • And so forth (a total of 26 conditions) *1993 CDC Surveillance Case Definition

  27. HIV Care in the Military • HIV positive persons may remain on AD status • Cannot serve overseas (policy being reconsidered) • Must attend 2-week “Initial” evaluation upon diagnosis at one of the 3 Navy HIV Clinics • 6-month and annual evaluations thereafter: • History and Physical • Laboratory evaluations including CD4 counts and viral load • Initial genotype • Annual syphilis test and PPD and basic lab tests • Initiate ARVs when appropriate • Vaccines • Treat any complications / other medical conditions • Social and mental health support • Education about HIV • Preventive Med sessions/safe sex • Medical Board if diagnosed with AIDS

  28. CD4 Count and Risk for Opportunistic Diseases • CD4 is the best measure for immune competence and stage of disease • Basis for treatment initiation • Closely related to risk for an opportunistic condition: • <200 • PCP • <100 • Toxoplasmosis • Cryptococcal meningitis/disseminated disease • Candidal esophagitis • <50 • MAC • CNS lymphoma

  29. Viral Load Viral load describes the rate of HIV progression Higher VLs are usually associated with faster declines in the CD4 count Not a primary reason to begin HAART

  30. History of Antiretrovirals 1st Drug: AZT, zidovudine March 1987 2nd NRTI: DDI, didanosine October 1991 Protease Inhibitors (Saquinavir) December 1995 Non-nucleosides (Nevirapine) June 1996 4th class: Fusion inhibitors March 2003 5th class: CCR5 inhibitors August 2007 6th class: Integrase inhibitors October 2007

  31. Fuzeon Entry inh Approval of Antiretrovirals Since ’95, 26 new products were introduced Truvada Combivir Viread Epzicom Epivir Rescriptor Emtriva Ziagen Selzentry Viramune Retrovir Videx Sustiva Trizivir Raltegravir ’04 ’05 ’06 ’87 ’88 ’89 ’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ‘00 ’01 ‘02 ’03 ‘07 NRTI Viracept Zerit Kaletra Reyataz NNRTI Fortovase Hivid Invirase PI Agenerase Prezista Lexiva Aptivus CCR5 Inh Norvir Crixivan Atripla Integrase Inh

  32. BENEFITS Control of viral replication easier to achieve and maintain Delay or prevention of immune system compromise Lower risk of resistance with complete viral suppression Decreased risk of HIV transmission RISKS Drug-related reduction in quality of life Greater cumulative drug-related adverse events Earlier development of drug resistance, if viral suppression is sub optimal Limitation of future antiretroviral treatment options Pros and Cons of Early Therapy

  33. DHHS/USPHS Guidelines Plasma HIV Clinical Category CD4 RNA Recommendation Symptomatic (AIDS, severe symptoms) Any Any Treat Asymptomatic <200/mm3Any Treat (14%) Asymptomatic >200/mm3 &Any Treat 350/mm3 ≥100,000 Defer (follow closely) Asymptomatic >350 Asymptomatic >350 <100,000 Defer therapy

  34. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR “NON-NUKE” BOOSTED PROTEASE INHIBITOR “PI” Recommended Regimens TWO NUCLEOTIDE/NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS “NUKES” + OR

  35. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

  36. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

  37. Protease Inhibitors (PIs)

  38. Recommended Regimens • Two nucleosides: • Tenofovir (TDF) & emtricitabine (FTC) [Truvada] • Zidovudine (AZT) & lamuvidine (3TC) [Epzicom] • PI or NNRTI: • Lopinavir/ritonavir • Atazanavir/ritonavir • Fosamprenavir/ritonavir • Efavirenz • Nevirapine (only use if CD4<250 in women or <400 in men) • 4 drugs are not better than 3!

  39. *First 1 pill a day for the complete treatment of HIV *July 2006 *Consists of tenofovir, FTC, and sustiva *$13,800/year Atripla™

  40. Medications to Avoid in Combination • AZT & D4T (antagonism) • D4T & DDI (toxicity) • Tenofovir & DDI (Poor CD4 response) • Tenofovir & abacavir (genetic fragility) • 3TC & FTC (same mechanism) • Triple nucleoside regimens (inferiority)

  41. Drug Resistance Testing If HIV viral load becomes “detectable” or the patient fails to suppress viral load, obtain resistance testing to guide therapy • Genotype and/or phenotype testing • Other indications for genotypic testing: • New “initial” patients • Rising rate of primary resistance (10%)

  42. Mutations Associated With PI Resistance NFV SQV IDV RTV FPV LPV ATV 30N 48VM 50V x x x x x x 50L High-level resistance 82ATFS 84VAC Intermediate resistance 90M Low-level resistance 46IL Mutated Position in the HIV Protease Gene 47A Contributes to resistance 47V 53L No resistance 54VTAS 54ML Hypersusceptibility x 23I 24I 32I 73CSTA 76V x 88S 88D 10IVFR 20MRIT 36IV 63P 71VTI 77I Stanford HIV Drug Resistance Database. Available at: http://hivdb.stanford.edu. Accessed July 24, 2006.

  43. Adverse Events Associated With Antiretroviral Therapies

  44. Fat Distribution ChangesLipohypertrophy

  45. Fat Distribution ChangesLipohypertrophy

  46. Fat Distribution ChangesLipoatrophy of the face

  47. HIV Treatment • New therapies • Novel locations in the life cycle of HIV to inhibit the virus’ replication (e.g., maturation inhibitors). • Penetration into HIV reservoirs: brain, genital area/secretions • Possible inducing latently infected cells into the the active cell population (Valproic acid) • Vaccines • No supporting data for good efficacy to date for prevention or for the treatment of HIV • HIV has many clades and subtypes to cover; in addition, each person has many quasispecies

More Related