Daniel C. Parker, MD
Michael A. Pontari, MD
ALERT
The American Urological Association (AUA) policy statement now considers circumcision to be of a health benefit, citing a50–60% risk reduction in HIV transmission in some African nations.
BASICS
DESCRIPTION
• HIV disease results from the acquired deficiency of cellular immunity caused by the human immunodeficiency virus (HIV).
– Hallmarks
Reduction of the helper T-lymphocytes in the blood and the lymph nodes
Development of opportunistic infections (Pneumocystis carinii pneumonia, cytomegalovirus infections, tuberculosis, candida infections, cryptococcosis, others)
Development of malignant neoplasms (non-Hodgkin lymphoma and Kaposi sarcoma)
• A spectrum of HIV infections range from asymptomatic seropositivity to AIDS
• Urologic manifestations of HIV/AIDS
– Bacterial and nonbacterial infections
– Urolithiasis
– Increased risk of malignancy
– Renal impairment
– Voiding dysfunction
EPIDEMIOLOGY
Incidence
40–50,000 new cases per year in US
Prevalence
• 0.5% of US adults <50 are infected
– 2.6% of African American men and 1.5% of African American women were HIV positive from 1999 to 2006
• 33.2 million people worldwide with HIV/AIDS
• 2.1 million deaths due to HIV/AIDS in 2007
RISK FACTORS
• Unprotected intercourse, anal or oral sex
• IV drug abuse and needle sharing
• Transfusion of blood products
• Concomitant STD/STI
• Uncircumcised phallus
• Transmission of mother to infant at birth or via breast milk
• Health care workers
– Risk for HIV after percutaneous exposure to HIV infected blood is 0.3%; after mucous membrane exposure 0.09%.
Genetics
• 3 groups of HIV viruses: M, N, and O
– Most infections are by class M
9 subtypes of M exist
– 15–20% genetic variation between viruses
PATHOPHYSIOLOGY
• HIV-1 binds to cells expressing CD4, leading to decline in CD4 cells and immune function.
• Immunosuppression allows opportunistic/unusual infections, decreases host defense against malignancy.
ASSOCIATED CONDITIONS
• UTI
– Greater if CD4 count <500/mm3
– Associated with typical bacteria (Escherichia coli, Enterococcus) and atypical pathogens such as fungi, mycobacteria, and viruses
• Epididymitis/orchitis
– Chlamydia, gonorrhea, salmonella, toxoplasmosis
• Fournier gangrene
• Prostatitis
– Up to 14% in patients with AIDS
– Greater risk in AIDS patients for developing prostatic abscess
• Urolithiasis
– Risk with use of indinavir or from metabolic abnormalities
• Hepatitis B virus (HBV)
• Malignancies
– Non-Hodgkin lymphoma
Usually B cell
May involve kidneys in 6–12% of AIDS patients
– Kaposi sarcoma
Up to 20% of untreated patients
– Testicular tumors
Usually seminoma
Up to 50 times more common
– Renal cell carcinoma
Up to 8-fold increased risk vs. noninfected individuals
• HIV associated nephropathy (HIVAN)
– Proteinuria >3.5 g/d, edema, and HTN
– Associated with focal segmental glomerulosclerosis (FSGS) on renal biopsy
– Progression to dialysis in <10 mo.
• Voiding dysfunction
– Can be retention, detrusor overactivity, and sphincter dyssynergia
GENERAL PREVENTION
• Barrier protection during sex (male and female condoms)
– Lab studies indicate that the female condom is an effective mechanical barrier to viruses, including HIV, and to semen.
• Avoid high-risk sexual behavior
• Male circumcision
– Although male circumcision should not be substituted for other HIV risk-reduction strategies, it has been shown to reduce the risk for HIV and some STDs in heterosexual men.
– Despite these data, male circumcision has not been demonstrated to reduce the risk for HIV or other STDs among men who have sex with men.
• Use of precautions by health workers
• Treating STDs
DIAGNOSIS
HISTORY
• Voiding history (1)[A]
– Dysuria
– Frequency
– Incontinence
– Urethral discharge
– Pelvic or testicular pain
– Flank pain
• Neurologic history
– Numbness
– Dysesthesias
• Social history
– Sexual history
– IV drug use
– Blood product transfusions
• Generalized lymphadenopathy, fever, weight loss, and chronic diarrhea are common symptoms.
• Review of systems (ROS): Constitutional symptoms, skin lesions, confusion, urticaria
PHYSICAL EXAM
• General: Skin lesions, adenopathy
• Neurologic exam: Numbness, alterations in sensation
• GU exam: Urethral discharge, testicular/epididymal exam for masses, prostate exam for nodule or tenderness
• Penile lesions of Kaposi sarcoma present as red/brown/purple nodules, macules, or patches
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• HIV testing
– Screening HIV-1 antibody titer
If positive, need confirmation by Western blot or immunofluorescence.
Need separate consent for HIV testing.
• UA, urine C+S
– May show rectangular crystals from indinavir
– Common bacterial pathogens in HIV-infected patients are E. coli, Enterobacter (enterococci), Pseudomonas aeruginosa, Proteus spp., Klebsiella, Acinetobacter, Staphylococcus aureus, group D Streptococcus, Serratia, and Salmonella spp.
– If UTI suspected and C&S negative, consider atypical organisms: Fungi, parasites, viruses
• CBC
• BUN/creatinine
• Specific testing for STD if urethral discharge present
Imaging
• With flank pain: Noncontrast CT
– Indinavir stones may not show on CT: Consider contrast study or retrograde pyelogram if renal impairment.
• Scrotal US for palpable lesions
• Prostate abscess: CT scan
Diagnostic Procedures/Surgery
• Measure PVR urine
• Urodynamics for voiding dysfunction or retention.
– Distinguishes bladder outlet obstruction from acontractile bladder if in retention
Bladder hypocontractility was seen in 35–45% at time of urinary retention (2)[A]
– Common urodynamic findings:
Hypo- and hyperreflexia
Acontractile hypoactive bladder
Detrusor-sphincter dyssynergia
Pathologic Findings
• Testicular tumors: Usually seminoma
• Lymphoma: B-cell non-Hodgkin lymphoma (NHL)
• Penile lesions: Kaposi sarcoma from lymphatic endothelial cells vs. squamous cell carcinoma
DIFFERENTIAL DIAGNOSIS
• Other systemic disease that cause fatigue: Chronic fatigue syndrome, others
• Salmonella epididymitis pathognomonic for HIV
TREATMENT
GENERAL MEASURES
• Refer to neurology, nephrology, infectious diseases when appropriate
• Patient education about risk factors, transmission
MEDICATION
First Line
• Highly active antiretroviral therapy (HAART)
– Combination therapy to combat the ability of HIV to generate drug-resistant mutants (3)[A].
– 10 million people now on antiretroviral therapy according to the WHO
– HIV therapy should be started in patients with:
AIDS
New WHO guidelines recommend starting therapy when CD4 count <500/mm3 (previous guidelines were <350/mm3)
Pregnant women
Patients with HIV nephropathy
Coinfection with HBV regardless of CD4 count.
New WHO guidelines also call for some people to begin treatment as soon as they test positive for HIV, regardless of CD4 count
Second Line
• General urologic conditions such as UTI, voiding symptoms, calcium stones treat as per general practice.
– Salmonella epididymitis
2–4 wk of doxycycline 100 mg PO BID plus Cipro 500 mg PO BID
If difficult to eradicate may need lifelong suppression.
• Kaposi sarcoma
– If focal, local radiation, cryosurgery, or retinoids.
– If disseminated use chemotherapy (doxorubicin) or immunotherapy with interferons
SURGERY/OTHER PROCEDURES
• Indinavir and other protease inhibitor (PI) stones
– Stop indinavir
– Hydration
– Stent if necessary
Stones are soft and may pass after stenting.
• Surgical drainage of prostatic abscess
• Stenting for ureteral obstruction from retroperitoneal NHL
ADDITIONAL TREATMENT
Radiation Therapy
Indicated in some cases of focal Kaposi sarcoma
Additional Therapies
• For health care worker exposure
• Post-Exposure Prophylaxis (PEP)
– Occupational PEP (“oPEP”), healthcare worker potentially exposed to material infected with HIV
– Non-occupational PEP (“nPEP”), someone is potentially exposed to HIV outside the workplace (eg, from sexual assault, unprotected sex, needle-sharing injection drug use).
– begin within 72 hrs of exposure; 2–3 antiretorviral medications for 28 days
• Pre-Exposure Prophylaxis (PrEP)
– For people who are HIV-negative and at substantial risk for HIV infection (relationship with HIV infected partner, gay or bisexual man who has had sex without a condom or been diagnosed with a sexually transmitted infection within the past six months, others
– Along with other prevention methods like condoms, PrEP can offer good protection against HIV if taken daily
Complementary & Alternative Therapies
None
ONGOING CARE
PROGNOSIS
Much improved prognosis leading to longer life expectancies, primarily due to newer drug combination therapies
COMPLICATIONS
• Antiretroviral therapy
– Risk of nephrotoxicity, crystal precipitation leading to stones, hypocalcemia
– Erectile dysfunction and decreased libido (caused by increased estradiol) may be associated with HAART therapy
• Drugs used for the treatment of HIV-infected patients have become the most frequent cause of drug-containing urinary calculi.
– Among these agents, PIs are well known to induce kidney stones, (indinavir, atazanavir, darunavir).
FOLLOW-UP
Patient Monitoring
• CD4 counts
• Serum creatinine
Patient Resources
• CDC HIV/AIDS Fact Sheets. http://www.cdc.gov/hiv/library/factsheets/index.html
REFERENCES
1. Breyer BN, Van den Eeden SK, Horberg MA, et al. HIV status is an independent risk factor for reporting lower urinary tract symptoms. J Urol. 2011;185(5):1710–1715.
2. Lebovitch S, Mydlo JH. HIV-AIDS: Urologic considerations. Urol Clin North Am. 2008;35(1):59–68.
3. von Wyl V, Yerly S, Böni J, et al. Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: A comparison of different regimen types. Arch Intern Med. 2007;167:1782–1790.
ADDITIONAL READING
• Cohen MS, Hellmann N, Levy JA, et al. The spread, treatment and prevention of HIV-1: Evolution of a global pandemic. J Clin Invest. 2008;118:1244–1254.
• Izzedine H, Lescure FX, Bonnet F, et al. HIV medication-based urolithiasis. Clin Kidney J. 2014;7(2):121–126.
• Millett GA, Flores SA, Marks G, et al. Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: A meta-analysis. JAMA. 2008;300:1674–1684.
• www.aidsinfo.nih.gov (Accessed August 11, 2014)
• www.cdc.gov/hiv/resources/factsheets/index.htm (Accessed August 11, 2014)
See Also (Topic, Algorithm, Media)
• HIV/AIDS, Urologic Considerations Image 
• Kaposi Sarcoma, Urologic Considerations
• Sexually Transmitted Infections (STIs) (Sexually Transmitted Diseases [STDs]), General
• Tuberculosis, Genitourinary, General Considerations
• Urolithiasis, Indinavir, and Other Protease Inhibitors
CODES
ICD9
• 042 Human immunodeficiency virus [HIV] disease
• 599.0 Urinary tract infection, site not specified
• 592.9 Urinary calculus, unspecified
ICD10
• B20 Human immunodeficiency virus [HIV] disease
• N20.9 Urinary calculus, unspecified
• N39.0 Urinary tract infection, site not specified
CLINICAL/SURGICAL PEARLS
• Urologic considerations in patients with HIV/AIDS include bacterial infections, urolithiasis, malignancy, renal impairment, and voiding dysfunction.
• Urolithiasis is associated with patients taking indinavir and other protease inhibitors (PI’s).
• HIV associated nephropathy (HIVAN) increases the patient’s risk of dialysis.
• Salmonella epididymitis is pathognomonic for HIV.
• Highly active antiretroviral therapy (HAART) increases estradiol and can lead to symptoms of erectile dysfunction and decreased libido.