Chapter 12: Urologic Implications of AIDS and HIV Infection

C Fitzgerald GCH Uro 1

Overview

Epidemiology Pathogenesis Natural history Diagnosis Urologic Manifestations Occupational risk factors Anti-retroviral therapy

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

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).

Co-factors in transmission

STI Endocervix > vaginal epithelium Circumcision Sexual behaviors (see table 12-2) Anti-retroviral therapy and secretion

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

HIV-1 or HIV-2HIV-1 Spherical shape Outer envelope Capsid with

ribonucleoprotein Glycoprotein

projections Catalytic enzymes

Reverse transcriptase Integrase Ss Viral RNA

HIV Replication Glycoproteins

gp41, gp120 Co-receptors

CCR5 CXCR4 C-type lectin

Fusion Viral uncoating

protease

HIV Replication Viral RNA ds DNA

Reverse transcriptase

Transport Cytoplasm nuclei

Integration host DNA Integrase 3’ end

Shedding

Latent pool Invisible to modern

anti-retrovirals Inborn errors

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

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%

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)

Question? + HIV Ab ELISA “-” Western Blot

Either false positive ELISA or acute infection

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

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

HSV

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

HSV

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

Syphillis

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

Chanchroid

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

Molloscum contagiosum

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

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

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

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

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

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

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%

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

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

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

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

Questions