Chapter 12: Urologic Implications of AIDS and HIV Infection C Fitzgerald GCH Uro 1.
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Transcript of Chapter 12: Urologic Implications of AIDS and HIV Infection C Fitzgerald GCH Uro 1.
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Chapter 12: Urologic Implications of AIDS and HIV Infection
C Fitzgerald GCH Uro 1
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Overview
Epidemiology Pathogenesis Natural history Diagnosis Urologic Manifestations Occupational risk factors Anti-retroviral therapy
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Epidemiology Diagnosed 1981 Prevalence: 34.6 to 42.3
million worldwide Incidence and mortality:
(2003) 4.8 M / 2.9 M -3 M /2.2 M Sub-saharan
Africa 2/3 all HIV-infected
individuals in Africa, reduced life expectancy by 15 yrs
#1 cause death men-2 women-largest African cities
Developed world deaths due to AIDS declining
US burden: 940,000 adults and children with HIV/AIDS
US incidence stable at 40,000 cases per year
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Transmissionmodes of transmission contact with blood transmission from
mother to child unprotected
intercourseGlobally, unprotected
sexual intercourse between men and women is the predominant mode of HIV transmission (WHO, 2004).
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Co-factors in transmission
STI Endocervix > vaginal epithelium Circumcision Sexual behaviors (see table 12-2) Anti-retroviral therapy and secretion
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Table 12-2. HIV Infection Risk Associated with Sexual Behaviors Compared with Blood Exposure
Route/Type of Exposure Risk of Infection Mean/Range (%)
Transfusion of contaminated
blood 84-100
Intravenous drug use (needle sharing)
0.8
Receptive anal intercourse 0.3-0.8 Insertive anal intercourse 0.04-0.1 Occupational needlestick exposure
0.28-0.33
Insertive vaginal intercourse 0.03-0.09 Receptive vaginal intercourse 0.005-0.02Insertive oral intercourse 0.003-0.008 Receptive oral intercourse 0.006-0.02
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HIV-1 or HIV-2HIV-1 Spherical shape Outer envelope Capsid with
ribonucleoprotein Glycoprotein
projections Catalytic enzymes
Reverse transcriptase Integrase Ss Viral RNA
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HIV Replication Glycoproteins
gp41, gp120 Co-receptors
CCR5 CXCR4 C-type lectin
Fusion Viral uncoating
protease
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HIV Replication Viral RNA ds DNA
Reverse transcriptase
Transport Cytoplasm nuclei
Integration host DNA Integrase 3’ end
Shedding
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Latent pool Invisible to modern
anti-retrovirals Inborn errors
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Pathogenesis Primary infection
Chronic asymptomatic
Overt HIV
Transient nonspecific febrile illness, mimics mono
Incubation 2-4 weeks, self limiting 14 days, lab assays usually neg
Clinically stable, serum CD4 stable
Extracellular HIV levels elevated; trapped in lymphoid matrix
Rapid increase in viremia Rapid fall in CD4 Immunologic deterioration
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Natural History Progression of disease~
time between detection and death HIV specific immune responses (without treatment) ~ 8-12 yrs (AIDS 2-3 yrs)
Median time conversion HIV AIDS
Typical 10-11 years; 60-70%
Rapid <5 years; 20% slow >15 years; 5-15% non-progressors never
progress; <1%
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Diagnosis Hx: isolated 1983, first diagnostic test 1986 3 categories; diagnostic assays, viral load, drug
resistance assays (rare)
Diagnostic assays ELISA ~100% specificity (two stage)
Blood Saliva Urine
Confirmatory Immunoblotting ie. Western Blot HIV viral RNA load (day 12, others 6 weeks)
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Question? + HIV Ab ELISA “-” Western Blot
Either false positive ELISA or acute infection
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Diagnosis Viral monitoring; baseline before
HAART, clinical stage, risk of disease progression (De Gruttola et al 2001), increase in drug resistance
Drug-resistance assays genotypic or phenotypic predominant species only pregnancy, salvage therapy +/-
community standard
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Urologic manifestations Primary infection:
viral exanthem (1-5 wks)
STI HSV – extended
course/increased severity, +/- resistance (Acyclovir parenteral, foscarnet, cidofovir)
HPV – unusual locations (lips, tongue..) higher risk recurrence after excision/treatment; CIN and SCC (see neoplasms)
Chanchroid – cofactor for HIV transmission; dx requires culture or painful ulcers supporative adenopathy and - HSV cx
Urethritis – STI vs Reiters syndrome
Molloscum contagiosum – pox virus found in10-20 % AIDS pt, CD4 < 250; dx histiologic
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HSV
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Urologic manifestations STI
HSV – extended course/increased severity, +/- resistance (Acyclovir parenteral, foscarnet, cidofovir)
HPV – unusual locations (lips, tongue..) higher risk recurrence after excision/treatment; CIN and SCC (see neoplasms)
Syphillis –chancre, expedited progression 2nd tertiary
Chanchroid – cofactor for HIV transmission; dx requires culture or painful ulcers supporative adenopathy and - HSV
Urethritis – STI vs Reiters syndrome
Molloscum contagiosum – pox virus found in10-20 % AIDS pt, CD4 < 250; dx histiologic
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HSV
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Urologic manifestations
STI HSV – extended
course/increased severity, +/- resistance (Acyclovir parenteral, foscarnet, cidofovir)
HPV – unusual locations (lips, tongue..) higher risk recurrence after excision/treatment; CIN and SCC
Syphillis –chancre, expedited progression 2nd tertiary
Chanchroid – cofactor for HIV transmission; dx requires culture or painful ulcers supporative adenopathy and - HSV
Urethritis – STI vs Reiters syndrome
Molloscum contagiosum – pox virus found in10-20 % AIDS pt, CD4 < 250; dx histiologic
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Syphillis
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Urologic manifestationsSTI
HSV – extended course/increased severity, +/- resistance (Acyclovir parenteral, foscarnet, cidofovir)
HPV – unusual locations (lips, tongue..) higher risk recurrence after excision/treatment; CIN and SCC (see neoplasms)
Syphillis –chancre, expedited progression 2nd tertiary
Chanchroid – cofactor for HIV transmission; dx requires culture or painful ulcers supporative adenopathy and - HSV
Urethritis – STI vs Reiters syndrome
Molloscum contagiosum – pox virus found in10-20 % AIDS pt, CD4 < 250; dx histiologic
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Chanchroid
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Urologic manifestationsSTI
HSV – extended course/increased severity, +/- resistance (Acyclovir parenteral, foscarnet, cidofovir)
HPV – unusual locations (lips, tongue..) higher risk recurrence after excision/treatment; CIN and SCC (see neoplasms)
Syphillis –chancre, expedited progression 2nd tertiary
Chanchroid – cofactor for HIV transmission; dx requires culture or painful ulcers supporative adenopathy and - HSV
Urethritis – STI vs Reiters syndrome
Molloscum contagiosum – pox virus found in10-20 % AIDS pt, CD4 < 250; dx histiologic
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Molloscum contagiosum
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Urologic manifestations GU tract Infections
Renal ie Tb, CMV, aspergillosis, toxoplasmosis
Prostatitis (8%) aerobes, anaerobes, fungi, mycobac
Epididymitis and Orchitis (39%)
Skin manifestations ie staph, nec fasciitis – Fourniers Tx surgical
Voiding dysfunction CNS/peripheral in
advanced disease retention (54%) detrusor hyper-
reflexia (27%) outflow obstruction
(18%)- Tx: meds, CIC,
suprapubic, UDS if severe
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Urologic manifestations Urolithiasis- Metabolic abnormalities Radiolucent stones
Indinavir - protease inhibitor; 2-24% nelfinavir and saquinavir can also cause
stones fluids, pain control, drug rest, +/- acidify urine (4.0)
Sulfadiazine for toxoplasmosis Tx: alkalinization
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Urologic manifestations HIVAN
Epi: 3.5% clinic patients, blacks>whites, IV DU
Clinical: nephrosis, RI, low CD4, low alb., edema, HTN, hyperchol, +/- hematuria, sterile pyruria
Tx: antiretrovirals delay onset +/- ACE I, ARB, immunosuppress tx
Abnl Urinalysis Hematuria** Pyuria Bacteriuria Proteinuria
**hematuria secondary to GU tumors uncommon in young males
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Neoplasms Kaposi’s Sarcoma
HSV 8 and HIV homosexual males
100,000:1 Decrease incidence w/
HAART Dx: Clinical or skin bx Tx: rad, laser, cryo,
chemo (Paclitaxel) avoid steroids
Rx: CD4 > 150 ~ 35 mo CD4 <150 ~ 12-13 mo
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Neoplasms NHL and
lymphoreticular malignancies Clinical sxs: fever, wt
loss, night sweats Widespread disease,
poor Rx NHL decrease with
HAART Dx: excisional bx Tx: chemo Mortality ~ 5-10 mo
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Neoplasms HPV
Anogenital pre/cancer
HPV 16, 18, 31, 45 Immunosuppression
correlates with occurrence and severity
Testicular Cancer 50:1 (Wilson et al) Germ cell and NGC Bilateral High grade
lymphoma Standard tx,
although tolerated poorly
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Table 12-4 HIV infection risk r/t exposure
Type of exposure Percutaneous Mucous membrane
Number of studies
27 21
Number of exposures
6807 2761
Documented infections
21 0/1
Infection rate per exposure
0.031% 0-0.11%
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HAART RTI nucleoside reverse
transcriptase inhibitors; competitive inhibition and block DNA elongation zidovudine, didanosine,zalcitabine, stavudine, lamivudine, abacavir
NRTI: Nucleotide reverse transcriptase inhibitor competitive inhibition and block DNA elongation tenovir disoproxil fumarate
NNRTI: Non Nucleotide reverse transcriptase inhibitor
competitive inhibition nevirapine, delavirdine, efavirenz
Protease Inhibitors block post translational processing saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir
HAART= RTI (x2) + PI or NNRTI
Combination therapies Combivir Trizivir Kaletra
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Antiretroviral therapyDeaths declining rapidly in Western
Europe and North American cities; but eradication not possible with existing therapies
HAART virus eradication ~ 50-60 years secoandry to CD4 t½~4 mo
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Antiretroviral therapy: side effects Zalcitabine:
peripheral neuropathy and painful penile ulcers
Ritonavir: high risk of bleeding
Indinavir: urolithiasis
Systemic SE: hypoglycemia, lactic acidosis, mitochondria toxicity
HAART Lipodystrophy
Atrophic: face and limbs
Hypertrophic: dorsocervical fat, breast
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Future strategies: vaccine (preventative
OR therapeutic) immune based
strategies that boost inherent protective responses ie pooled immune sera or monoclonal antibody transfers
Vaccine trials underway
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Questions