HIV and AIDS

Human Immunodeficiency Virus is a retrovirus that destroys CD4 T cells and is the etiologic agent of Acquired Immunodeficiency Syndrome. First identified in 1981 in the US. USA also has the most severe epidemic in the developed world of HIV. Introduction/definiti on

May have been around since ca. 1965 (Type I) Traced to chimpanzees
AIDS is a constellation of opportunistic and other infections, hypersensitivities, and unusual malignancies that occur as a result of increasing immune depletion. Most infections are in Sub-Saharan Africa, Carribean is #2. HIV infections peaked in the late 1990s and stabilized, but rising again many places

HIV is a Group D retrovirus, a lentivirus. Retroviruses use reverse transcriptase (RNA-dependent DNA polymerase) to replicate. They can also insert their genetic code into host DNA. Lentiviruses have a lipid envelope and a dense cylindrical core, and can become latent in the host, leading to lifelong infection. Other retroviruses that mess with humans o HTLV-I causes lymphoma, not AIDS. o There are several viruses in this group that cause

Etiology

cancer and immortalize lymphocytes, but HIV kills lymphocytes. HIV-1 is classic aids virus and is what we know in the US and in the global epidemic, but HIV-2 is seen in West Africa, and seems to have a slower progression of disease. The only difference in the viruses is in the viral envelope.

HIV was once known as: o LAV - lymphadenopathy associated virus o HTLV-III - human T-cell leukemia virus III o ARV - AIDS associated retrovirus o HIV - (official name)

33 million world-wide (2008) 64% in sub-Saharan Africa where 33% of deaths occur High risk populations o Organ transplantation-Window time period between infection and positive test. o IVDU-Shared needles and sex o Hemophiliacs and blood transfusion recipients* ---not as much now as before because of screening of blood products o Perinatally---children of positive mothers can be positive on titer without the virus-but they also could have it. o Coexistant STD-easier to transmit to and from because of less barrier Blood, semen, vaginal secretion, and breast milk 1o. These are the PRIMARY transmission routes. Low risk with decreased viral load o < 1700 copies - risk 1:10K o >38,500 copies - risk 1:294

Epidemiology

Cultural factors Numbers rise despite meds, due to cost to treat and/or prevent, cultural issues, and access to medications. 4 million in developing countries at the end of 2008 were being treated despite higher incidence. Explosion of cases in Asia, Western Europe, Russia, sub-Sahara Africa Lower numbers of infections in Iraq and Iran likely due to different cultural practices Teens 3x more likely to acquire than adults, according to Uganda study in 2000. Dated, but principle is still there 1.4 million cases in the USA o Black women 10 x more likely to have HIV than whites

Pathobiology/patho physiology (design flaw that helps organism infect you)

Virus can infect all cells displaying the CD4 antigen, which HIV uses to attach to the cell. T4 helper T lymphocytes are infected and those direct lots of other actions of the Chemokine co-receptors CCR5 and CXCR4 are required for virus entry (people who have CCR5 deletions are less likely to be infected with the disease and if they are, it progresses slowly) Other cells like B lymphocytes and macrophages are also infected. Dendritic cells (APCs associated with mucosal areas)spread HIV which isnt killed by them. They present it in the lymphatic system, it spreads to other areas and kills T4 cells. Macrophages act like a reservoir and can send it to other organ systems like the CNS HIV causes immunosuppression and also neurologic defects because infected macrophages release cytokines and neurotoxins, and also messes up neurotransmitter release and Calcium levels. HIV also directly infects renal tubular cells and GI epithelium and manifests in these organ systems.

Found in blood, semen, saliva, tears, CSF, vaginal secretions, breast milk, urine, T-lymphs, macrophages, and brain cells

Transmission: Sexual: Semen, vaginal secretions. Blood o A documented case by which it was spread by toothbrush. (bleeding gums) Pathogenesis o Can be spread by razors. (how it gets into the o Infected blood products (now tested, so this place it infects in is lots lower) body) o IV drug use o Blood to blood. Skin bleeds. Vertical transmission o Transplacental o During childbirth o Breast milk No evidence of casual contact, tears, saliva or sweat (if no blood or other stuff involved)

Symptoms Degree of immunosuppression determines clinical manifestation and symptoms May be asymptomatic for several years often up to a decade. Headache. o T. gondii - most common encephalitis o C. neoformans most common meningitis Symptoms and signs (history and physical) Fever, malaise, night sweats, confusion. Perirectal pain, diarrhea (could have salmonella, shigella, helminths, etc.) Vision problems (microvascular disease, retinitis from CMV) Lymphadenopathy, 2 extrainguinal sites especially lasting over 3 months. Spots on the skin-KS Dysphagia, acute abdominal pain.peritonitis

Signs Appearance of associated disease patterns that would be unusual otherwise. Opportunistic processes like candida, multifocal leukoencephalopathy, cryptosporidiosis, azole resistant candida esophagitis. KS, HZV zoster more virulent, worse preexisting lesions, drug eruptions. Hypersensitivities, malignancies, and opportunistic or overwhelming infections Lymphadenopathy-extra suspicion if its lasting more than 3 months.

 Pneumocystis Jirovecii very dangerous opportunistic illness that is AIDS defining. Very common. Treat with Bactrim, can do prophylaxis with Bactrim. Oropharyngeal thrush: also very common *NOTE: the 2 above are unclear from our text which is most common aids defining versus most common OI and in pharm it may have been different. Ill email Doc Kaposis Sarcoma: looks like big purple blotches. Its skin cancer caused by Human Herpes Virus 8.

Most common associated diseases and syndromes

T. gondii - most common encephalitis C. neoformans - most common meningitis Primary CNS lymphomacan be a ddx? Look up!!!! Dementiaalarming in a young person, this is not normal. Suspicious of HIV, because HIV can cause it. Esophagitis o Candida 50-70% o CMV 10-20% Diarrhea caused by salmonella, shigella, Eye o Microvascular disease most common o CMV retinitis most common infection of the retina VZV and Toxoplasmosis also HIV accelerates the course of Hep B and C IV drug use/STD situation Definitely check for these. May have a primary hepatoma. Not easy to treat. And the liver has to metabolize the medications the HIV person has to be on too so you really dont like a sick liver here Neurological complications o Not only consider HIV effects but a broader diff. consisting of CVA and degenerative diseases related to IVDU, intoxication, and nutrition

Labs

ELISA and Western Blot/IFA positive with viral loads are diagnostic of HIV infection. No question, if these are positive, they have it. 95% of HIV infections are caught by ELISA at 6 weeks. Sensitivity is 99.9% and Western Blot confirms. P24 HIV-1 RNA antigen. Positive earlier because of immune response, but the ELISA and Western Blot are absolute confirmation. Diagnosis is made when either the presence of an AIDS defining infections is confirmed or the T4 count drops below 200, OR is less than 14% of the total lymphocyte count. If AIDS defining syndrome/low T4 are present, the timing no longer matters. They are full blown AIDS. 50 cells/mm cubed is advanced HIV disease. Get T4 count, viral load, exclude ddx, ID treatable components, diagnose life threatening conditions and CNS involvement. CBC, liver, kidney function, etc. Check for toxo, do PPD, syphilis test, hepatitis ABC tests. ELISA Western blot / IFA HIV RNA load CD4 (T4) CBC T4 / T8 Protein electrophoresis Bone marrow CAT brain <500 to >30K copies <200 to >500 WBC <3000 Thrombocytopenia T4 < T8---Normal is 2:1 but if reversed suspect HIV Polyclonal gammopathy

Fiebig Stages

Eclipse phase: around 7-21 days after exposure, and lasts around 10 days. Eclipse to Stage I Asymptomatic, Carrier like state. Window period, not going to show up on tests, and you wont feel odd or anything. Stage I to II or III vRNA test will be positive at stage I-III. Between II and IV, p24 antigen will be positive, and at stage III and beyond, ELISA antibody will be positive. Acute viral syndrome, fever, may have lymphadenopathy, rash first, then malaise and then a temp. recovery. Seems like ANY virus. Think you had the flu or something. Acute viral syndrome is just a general response your body tends to have to a virus. May seem like a flu that hangs on. HISTORY is very important, such as history of other STD, exposure, etc. Stage IV to VI P24 antigen positive, ELISA antibody is positive, Western blot may be positive beginning at age IV. AIDS related complex (ARC) and AIDS prodrome. Persistent lymphadenopathy. Theres a differential though, that could be cancer, HIV, etc. Beyond Stage VI Western Blot and ELISA should be positive. Fever, Wt loss, Diarrhea, Malaise, Oral thrush All have Ab to virus Onset gradual or abrupt Burkitts lymphoma, Non-Hodgkins, HZV, HSV Cutaneous fungal-not athletes foot but intertrig areas Oral Hairy Leukoplakia (caused by EBV), Idiopathic thrombocytopenic purpura (ITP)

Prevention

Needle stick exposure in healthcare workers is 3 per 1000 (0.3%) Still relatively low but because of safety precautions. Reduced with prophylaxis some medications (antiretrovirals) given in certain populations because of practices, or if you get a needle stick or something. Prevention is cornerstone to the approach of HIV o Abstinence o Monogamous relationships o Dont share needles o Autologous transfusions in procedures. (not needed as much now, but an option) Post exposure prophylaxis o Depends on depth of penetration, what part of body exposed, blood sprays depend on amount of blood and where exposed. o HIV status of person known at the time/months and years later o P 2184 for more info

Treatment

Even though we have drugs that knock down the virus, we cant mitigate the irreversible effects of the disease. They increase the T4 count, but it is NOT A CURE Antiviral regimen EFV/TDF/FTC, etc. p 2188. Supportive, psych care Keep them comfortable by supplementing oxygen or knocking out opportunistic infections, Nutritional supplements Drugs are best when you intervene early in the infection and choose drugs that suppress virus below level of plasma detection. Does not mean youve eliminated it from lymphoid tissue or CNS. Always assume pt. can transmit HIV Antiretroviral drugs are advised for all patients with plasma viral load over 30,000 and T4 count under 350. Higher levels have no recommendations but do it anyway if patient wants treatment. Opportunistic infection prophylaxis decisions see page 2187-88

Prognosis

Terrible. Antiretrovirals help extend life but there is no cure. Under 500 copies/ml is better for prognosis of the disease. 500-10,000 moderate level of infection. 10,000-30,000 copies Over 30,000 copies/ml is a heavy infection, high viral load and is more likely to have a rapid downward turn in clinical status T4 count under 200 not a good prognosis 200-500 okaynot great Over 500 T4 cells= ideal. Keep them like this. Poor T4 responses to treatment is bad prognosis. Need to switch drugs. This is a predictor of clinical response to anti-retrovirals. Older age-immunity not as good anyway High HIV RNA levels-poor prognosis Hepatitis C co-infection- need liver for drugs, and youre fighting 2 things.