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Clinical Manifestations of HIV Ardis Ann Moe, M.D. Center for AIDS Research and Education Summary • Know Who to Test • Know Early Warning Signs of HIV • Absence of Risk Factors Does Not Mean Absence of Whoops Factors • D.W., Diagnosed with AIDS 1993. CD4 count 110. – Develops PCP, MAC, wasting disease, peripheral neuropathy – Tried on multiple HIV regimens: AZT, D4t+3TC, and various protease inhibitor combinations beginning 1996 • Now has MDR-HIV, CD4 count 8 in 2001. • Begun on T-20, abacavir, 3TC, tenofovir, lopinavir/ritonavir and soft gel saquinavir • ($50,000/year treatment) • CD4 count now 256, viral load undetectable. MAC resolves. • Working part time, raises 2 children. Wife still HIV• Diabetes, cholesterol 356, triglycerides 780, Cr 1.9, facial wasting. Epidemiology • 900,000 persons with HIV in US, 1/3 unaware • Over half of new infections are among African-Americans, and 30% of new infections are in women • MSM 42%, IDU 25%, heterosexuals 33% • Young MSM African-American men in New York; rate of seroconversion 15%/year • Young MSM crystal meth users in Los Angeles; rate of seroconversion 20%/year • Overall increase in number of new HIV and AIDS cases • Seroconversion parties: bug-chasers and gift givers • Complacent attitude fostered by glowing advertisements of perfect health while on HIV medications • Drug use drives much of this epidemic, directly or indirectly • Death rate about 15,000/year • 40,000 new HIV cases/year • Liver failure and bacterial pneumonia now leading causes of death; OI related deaths now less than 1/3 of cases Routes of Transmission • Blood products (100%) • Pregnant mom to unborn child (40% if breast feeding) • Receptive anal intercourse(1%) • Shared IDU(1%) • Needlesticks(1/300) • Insertive anal intercourse(1/1,000) • Male to female = female to male (IF male is uncircumscised) (1/1000) • Oral-genital sex (1/10,000) • Shared razors • Shared toothbrushes • Exposure to open skin lesions How to Prevent Transmission • • • • • • Counsel at-risk groups Offer HIV testing to all pregnant women PEP for needlesticks (within 1 hour) Treat infected persons with HIV meds Reduce drug use in community Treat STD’s When to Offer HIV Testing • Shingles in person <60 • Recurrent, unexplained vaginal yeast infections (3+/year) • All pregnant women • Gay/bisexual men • • • • • Unusually severe ear or sinus infections Failure to thrive in children Persistent diarrhea Unexplained weight loss Unexplained lymphadenopathy • Person of African race with unexplained kidney failure • FUO • Bacterial pneumonia in healthy young person • TB • • • • Primary pulmonary hypertension Idiopathic Thrombocytopenic Purpura Severe Seborrhea Unexplained persistent leukopenia • Any history of any STD, including warts, hepatitis A, B, C, or GI parasites • History of unexplained enteric infections, especially Shigella • Thrush • B cell lymphomas • • • • • Jail Homeless Cocaine use Crystal meth or other substance abuse And anyone who asks for an HIV test! Types of HIV Tests • • • • • Elisa with Western blot or IFA Anonymous vs Confidential Testing Rapid HIV tests becoming more available Home HIV tests Urine and saliva HIV tests • M.V. 65 yo male presents for routine heart valve surgery. Married, retired MD. – Housestaff get HIV test without patient’s consent. Patient is HIV+, CD4 count 420 Clinical Signs of HIV • Onychomycosis – Often seen in diabetics as well – Indefinite treatment with itraconazole, lamisil, etc. Scabies • Can be widespread over entire body, with heavy encrustations of organisms: “Norwegian” scabes Looks like severe psoriasis • Patients should be isolated • Shingles – Rare in young persons, but can occur in up to 10% of HIV+ persons – More likely to occur when HIV meds started – Shingles of the face may cause blindness from corneal involvement – Shingles may cause secondary skin infections from staph, Group A strep • Warts – HPV can be widespread – Cause of cervical cancer, and now responsible for increasing number of cases of anal cancer in HIV+ men – Tends to recur; difficult to eradicate • Peripheral neuropathy – Can occur in up to 1/3 of HIV+ persons – Many causes: HIV, CMV, diabetes, INH, HIV meds, alcohol, etc • Thrush, vaginal yeast infections – Thrush usually occurs in the mouth a few months to a few weeks before PCP or other AIDS OI occurs – Women have more severe and difficult yeast infections • Primary pulmonary hypertension – Most cases occur in women – Reversible with HIV medications – Unknown mechanism • ITP – Auto platelet antibodies from HIV stimulation of the immune system – Best treated with HIV medications and gamma globulin; possible splenectomy Opportunistic Infections • T.W. 25 yo woman presents with DOE and fevers in 1997. CD4 count 45. Boyfriend died of PCP in 1995. • PCP has 50% mortality if diagnosed late; 5% mortality if diagnosed within 3 days of admission • Can present as normal CXR, normal LDH, normal ABG’s • Most commonly presents as unusually severe DOE, cough and fever in previously healthy person. CD4 count <200 • Can cause pneumothorax • May be unilateral, apical, or with a pleural effusion • Usually dry sputum production, but bacterial pneumonia often co-pathogen • T.W. now with CD4 count 850 on HIV meds, completed MBA, married, undetectable • She did not face up to her AIDS until she got the same pneumonia that killed her boyfriend • TB – Tenfold risk of progressive TB infection if PPD positive (5 mm induration) – More likely to have atypical presentation: • Spine TB, TB pericarditis, lower lobe infiltrates • DOT therapy standard of care • J.F. 31 yo male presents with paraplegia 1996 CD4 count 11. – – – – TB of lower spine and skull Treated with 4 TB drugs and HIV medications Finally learns to walk again after 5 months. Working full time now Bacterial pneumonias • K.L., 37 yo married woman presents with lobar pneumona. Previously healthy. • CD4 count 340, HIV+ • Husband HIV-, no other sexual partners, no drug use, no transfusions, no needlestick injuries (UCLA care partner) • Treated in Kenya for malaria with cholorquine injections • Doctor gave her AIDS from a dirty needle • She is classified as an IDU risk factor • 1 of 7 deaths in AIDS still due to bacterial pneumonias: unchanged since 1987. • No effect of HIV meds seen • Flu vaccines, pneumovaccines helpful • HIV infected persons more likely to have PCN resistant strains • Kaposi’s Sarcoma – Caused by HHV8 and co infection with HIV (or other immune suppression) – Usually presents on legs, arms, tips of ears. – Can involve lymphatics and cause massive leg edema – Deaths usually from lung involvement • Treated with chemotherapy (IV and topical) – Radiation therapy to face helpful – HIV meds alone will treat 1/3 to ½ of cases – Also a sexually transmitted disease • R.S. presents with new KS of his legs in 1983 – Finally dies of bacterial pneumonia at age 61 in 2003 – Worked full time until day before death • Mycobacterium Avium Complex – Blood, lymph nodes, liver, spleen most often infected – Presents as fever, night sweats, anemia, hepatosplenomegaly in persons <50 CD4 cells • CMV – Usually presents as a retinal infection with “floaters” in persons <50 CD4 cells – Can also involve brain, intestines, esophagus • R.G. – 41 yo male with CMV retinitis and CMV encephalitis in 1996. Comatose – Sent to nursing home to die and started on triple-drug therapy as a trial • 1 month later, becomes a major irritant to the nursing staff, who discharge him home • Toxoplasmosis – Parasite found in soil, cat feces, undercooked meat – 15% of US population colonized – Presents as seizures, focal neurologic signs and fever in persons <100 CD4 cells • Occasionally presents as pneumonia or retinal disease • Treated with sulfadiazine and pyramethamine • S.M. 32 yo male, CD4 #10 1996 – Developed toxoplasmosis and has residual basal ganglia injury – Parkinson’s disease and permanent stutter • Multiple ring enhancing lesions on CT with contrast • Can occur with other CNS diseases: cryptococcus, CMV, lymphoma • HIV encephalitis – Progressive loss of brain cells and encephalopathy due to cytokine poisoning – Partially reversible with HIV medications – Limited number of HIV meds penetrate bloodbrain barrier • Cryptococcal meningitis – Presents as fever, AMS, neurologic deficits, seizures in persons CD4 <70 – A.H., 41 yo male, HIV+ x 8 years. Refuses meds – Brought in by wife in coma. +cryptococcal meningitis • Requires repeated lumbar taps to decrease brain pressure • Treated with 2 weeks of ampho B and 5 FC • Recovers and back working full time • Progressive Multifocal Leukoencephalopathy – – – – Caused by JC virus, CD4 <50 Rapid loss of function—stroke-like events Residual personality changes, blindness Survival 50% at 1 year even with HIV meds • If HIV untreated, survival 4 months • G.I., 55 yo woman. In Hospital 9 months for unexplained weight loss and leucopenia • Finally gets HIV test and diagnosed with PML. • Fed through G-tube x 3 months • After HIV meds and treatment with cidofovir and steroids, learns to feed herself and walk after 6 months. • Takes dancing lessons and moves to Rome because the shopping is better • Still mad at me for taking away her driving license • Lymphoma – Hodgkins and non-Hodgkins lymphomas – Usually B-cell – CNS lymphoma almost always associated with AIDS – Rapid progression to death unless AIDS and lymphoma can be aggressively treated • L.M., 33 yo male with AIDS and MDRHIV – Presents with vertigo July 22, 2003. MRI normal – Presents with diplopia August 1. New mass on MRI – Dead from lymphoma August 19. • Cryptosporidium – – – – Intestinal parasite, traveler’s diarrhea Cholera-like secretory diarrhea Up to 17 liters of diarrhea/day Only known treatment: HIV medications to improve immune system – CD4 count <150 • L.O. 47 yo male – Presents with cryptosporidium diarrhea in 1994 – Treated with TPN. Multiple line infections – Dead in 6 months • Wasting disease – Progressive loss of muscle mass – Usually associated with chronic diarrhea – Multifactorial causes: food issues, dysphagia, OI’s, HIV virus, low serum testosterone in men. HIV Treatment Related Problems • Lipodystrophy – – – – Fat accumulation Lipoatrophy Diabetes Elevated cholesterol and triglycerides • 75% of all patients on protease inhibitors will have some problem with fat accumulation or fat wasting after 2+years of protease inhibitor therapy. – Some contribution from stavudine • Fat accumulation syndromes may be due to interference between HIV protease inhibitors and natural proteases that digest fat molecules • Fat atrophy syndromes may be due to mitochondrial toxicity • 55% of persons on protease inhibitors will develop insulin resistance within 4 weeks of treatment • 16% develop elevated fasting glucose • 7% develop frank diabetes • Partially reversible by stopping proteases • Family history, gender, race, obesity all factors as well • HIV virus itself – HIV+ persons have elevated triglycerides, low HDL cholesterol and more facial wasting than HIV- persons, regardless of treatment • White males over 40 more likely to develop facial wasting • Obese African American women most likely to develop fat accumulation and diabetes (neck collar fat, breast enlargement) • Avascular necrosis – – – – Usually presents as sudden hip pain in men Risk factors: use of prednisone, weight lifting ?megace, androgens Seen before protease inhibitors • Only treatment is with hip replacement or other hip surgery • Lactic acidosis – Caused by all nucleoside-based HIV medications – Most commonly seen with D4T, DDI, and DDC – Can cause death within 48 hours – Indistinguishable from sepsis • Treated with removal of HIV medications and IV thiamine, riboflavin and L-carnitine • Low level lactic acidosis may be causing osteopenia in long-term HIV survivors • Overall, survival of persons with AIDS dramatically improved • 6 month survival in 1985 to 17+ years • #1 cause of death in young adults in US in 1995 to #14 cause of death 18 months later • Key factor is to test persons who are at risk for any reason, and refer for evaluation • Treatment now delayed until CD4 count <350, or symptomatic from HIV, or pregnant • Studies on treatment interruptions ongoing.