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 blood-

brain 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 MDR-HIV– 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.