Urinary tract infections

Patients who have HIV experience a greater risk of urinary tract infections (UTIs) when their CD4 counts fall below 500/mm ³ . Voiding dysfunction with urinary stasis is also implicated as a factor in the increased incidence of UTIs in HIV-positive patients . A 17% incidence rate of UTI is seen in HIV-positive patients . Patients may have bacteruria and be asymptomatic; however, common symptoms include dysuria, frequency, fever, and hematuria . Patients with asymptomatic bacteria may not require treatment . Common bacterial pathogens in HIV-infected patients are Escherichia coli , Enterobacter (Enterococci), Pseudomonas aeruginosa , Proteus spp, Klebsiella , Acinetobacter , Staphylococcus aureus , group D Streptococcus, Serratia, and Salmonella spp .

Disseminated infections may affect potentially any portion of the urinary tract. They are usually caused by atypical organisms and frequently associated with a depressed immune system. Atypical pathogens may include fungi ( Candida albicans , Aspergillus, Blastomyces , Cryptococcus neoformans , Cryptosporidia , Histoplasma capsulatum ), parasites ( Toxoplasma gondii , Pneumocystis carinii ), mycobacteria ( Mycobacterium tuberculosis , Mycobacterium avium complex), and viruses (cytomegalovirus and adenovirus) . Patients with urinary symptoms and negative urine culture results should be evaluated further with atypical culture and stain analysis. Treatment with culture-sensitive antibiotics is recommended when available.

Epididymitis, orchitis, and necrotizing fasciitis

Many HIV-positive patients present with inquiries about urethral infections related to sexually transmitted diseases, such as Chlamydia trachomatis and Neisseria gonorrhoeae . These infections can propagate and spread to cause epididymitis-orchitis. Other opportunistic and systemic infections lead to abscess formation in the penoscrotal region. Organisms associated with suppurative and antibiotic resistant infections in this population include cytomegalovirus, Candida , mycobacterium, Toxoplasmosis , and Salmonella . These infections, especially Salmonella , may be difficult to eradicate and require lifelong suppressive therapy. Initial treatment recommendations include a 2- to 4-week regimen of doxycycline, 100 mg, twice daily and ciprofloxacin, 500 mg, twice daily .

Depending on the severity of the infection and how immunocompromised an individual is, necrotizing fasciitis of the genitalia or Fournier’s gangrene may develop . This aggressive infection may be the initial presentation of a patient who has HIV. Immediate diagnosis with wide surgical débridement to healthy and viable tissue is necessary. Broad-coverage antibiotics are used until the organism and its sensitivities are obtained. Patients may require aggressive hemodynamic support, and multiple surgical débridements may be necessary. A diverting colostomy and eventual skin grafts may be necessary for appropriate healing to take place.

Epididymitis, orchitis, and necrotizing fasciitis

Many HIV-positive patients present with inquiries about urethral infections related to sexually transmitted diseases, such as Chlamydia trachomatis and Neisseria gonorrhoeae . These infections can propagate and spread to cause epididymitis-orchitis. Other opportunistic and systemic infections lead to abscess formation in the penoscrotal region. Organisms associated with suppurative and antibiotic resistant infections in this population include cytomegalovirus, Candida , mycobacterium, Toxoplasmosis , and Salmonella . These infections, especially Salmonella , may be difficult to eradicate and require lifelong suppressive therapy. Initial treatment recommendations include a 2- to 4-week regimen of doxycycline, 100 mg, twice daily and ciprofloxacin, 500 mg, twice daily .

Depending on the severity of the infection and how immunocompromised an individual is, necrotizing fasciitis of the genitalia or Fournier’s gangrene may develop . This aggressive infection may be the initial presentation of a patient who has HIV. Immediate diagnosis with wide surgical débridement to healthy and viable tissue is necessary. Broad-coverage antibiotics are used until the organism and its sensitivities are obtained. Patients may require aggressive hemodynamic support, and multiple surgical débridements may be necessary. A diverting colostomy and eventual skin grafts may be necessary for appropriate healing to take place.

Prostatitis

The algorithms used to treat basic urologic conditions, such as prostatitis and chronic pelvic pain syndrome, in HIV-positive patients are similar to those used to treat non–HIV-positive patients. In treating HIV-positive patients, however, evaluation and treatment of atypical organisms frequently are warranted. The incidence of acute bacterial prostatitis is 1% to 2% in the general population, whereas it is 3% in asymptomatic, HIV-infected patients and 14% in patients who have AIDS . These data predate treatment with HAART and likely are currently lower in incidence. Patients who have acute prostatitis may experience fevers, dysuria, frequency, malaise, urinary retention, and perineal pain . Digital rectal examination may indicate an enlarged, tender, and potentially fluctuant prostate . In patients who have HIV, the risk of developing a prostatic abscess or urosepsis is greater than in the general population because of the atypical pathogens previously mentioned. They require increased monitoring and evaluation and likely an extended duration of culture-specific antimicrobial and antifungal therapy . If surgical intervention to drain a prostatic abscess is necessary, it can be accomplished by either transrectal or perineal aspiration or transurethral resection. Symptomatic and disseminated fungal infections may require long-term antifungal-directed therapy and prostatectomy . As with all infections in immunocompromised patients, atypical pathogens always should be considered.

Urolithiasis

Patients on HAART therapy are managed with protease inhibitors, which act by preventing terminal maturation in the formation of new viral particles and are implicated as a cause of urolithiasis . Indinavir, a protease inhibitor that has been well investigated, is known to cause urolithiasis in 5% to 25% of HIV-positive patients . Metabolized mainly by the liver, 20% of indinavir is not metabolized and is excreted in the urine within 24 hours . Indinavir crystallizes when the pH of urine is more than 5 and the concentration is sufficient. Indinavir, as a stone component, is seen only in 29% of calculi. The remaining stone components are calcium oxalate, ammonium acid urate, and uric acid . Although uncommon, pure indinavir calculi are radiolucent on radiographic studies and there may be minimal findings on noncontrast CT studies .

Patients who have HIV also have metabolic imbalances that may result in calculi formation. Disturbances from malnutrition and diarrhea play a role in dehydration, increase in urinary concentration, acidification, and hypocitraturia . In this metabolic state, stone formation is promoted. Patients may present with flank pain and microscopic hematuria, which requires intravenous urogram, renal ultrasonography, or a noncontrast spiral CT scan. Renal collecting system dilation may be the only radiologic finding in patients with indinavir calculi, whereas other components are seen as calcifications . Conservative measures with hydration and analgesia may be effective in up to 80% of patients .

Once diagnosed with calculi, patients should undergo a complete metabolic evaluation. Recommendations include not only stone analysis but also two 24-hour urine collections for volume, calcium, oxalate, uric acid, magnesium, phosphorous, and sodium. Serum studies should be examined for blood urea nitrogen, creatinine, calcium, and serum electrolytes . Recently, investigators looked at the early plasma trough levels of indinavir in patients receiving 800 mg of indinavir three times daily as a first-line protease inhibitor. Higher trough levels were associated with a higher rate of severe nephrolithiasis and a higher rate of all serious adverse reactions. Recommendations based on these conclusions included early indinavir trough determination and dose adjustment . Stopping indinavir did not result in complete resolution of calculi formation or complications associated with them; therefore, patients rarely need treatment with an alternative drug .

When conservative management does not lead to resolution of symptoms or if a patient becomes acutely ill because of intractable pain, UTI, or high-grade obstruction, temporary stenting or nephrostomy tube placement is necessary. Manipulation with endoscopic stent placement may be enough to allow passage of these soft and gelatinous matrix stones, as in the case of pure indinavir stones . Occasional ureteroscopic or percutaneous nephrolithotomy may be necessary for stone extraction.

Sexual dysfunction

ED and hypogonadism are recognized conditions in men who have HIV. Testicular atrophy is common and leads to infertility, ED, and decreased libido . In one study that examined serum testosterone and ED in 300 such patients, 17% of men were hypogonadal. Increasing age and body mass index were positively associated with hypogonadism. The authors found no association between ED or hypogonadism and HIV therapy .

Testosterone supplementation has been used in testicular and hypothalamopituitary diseases for several decades. There has been growing interest in the use of testosterone in male contraception, aging, muscle-wasting conditions such as HIV, and ED . The new transdermal patches, gels, and sustained-release buccal tablets are designed to provide testosterone levels that are close to normal physiologic levels . These treatments, in addition to phosphodiesterase type-5 (PDE-5) inhibitors, can effectively treat men who have HIV and suffer from low libido caused by low levels of testosterone and ED.

Effective treatment of ED actually can be a factor in spreading the HIV virus. In one study by Karlovsky and colleagues , data obtained from the Centers for Disease Control and Prevention (CDC) in Atlanta demonstrated an increased incidence of gonorrhea among elderly men living in south Florida. Gonorrhea is a vehicle of transmission for HIV. Although there was not a direct correlation between the use of PDE-5 inhibitors and the increasing incidence of HIV among elderly men in south Florida, the association was suggested. Possible reasons may be that these elderly men grew up in the age before universal precautions and currently engage in risky behavior. Another example, in a study by Benotsch and colleagues , which discussed 304 homosexual men who engaged in sexual activity while on vacation or business trips, concluded that men who were taking PDE-5 medications reported higher rates of sexually risky behaviors.

HAART also plays a role in sexual dysfunction. Lamba and colleagues found the incidence of ED and decreased libido in HIV-positive homosexual men to be 26%. In that study, in patients who were taking HAART, the incidence of reduced libido was 48% (caused by raised estradiol levels) and the rate of ED was 25%. Studies support and oppose the occurrence of sexual dysfunction in HIV-positive men taking HAART . PDE-5 inhibitors also may have an interaction with indinavir and other protease inhibitors. In a report by Murray and colleagues , indinavir was a potent inhibitor of the hepatic mechanism of sildenafil. They suggested that starting sildenafil at a lower dose would be more appropriate in patients taking indinavir.

Men who are HIV positive are more likely to experience depression . Depression is associated with low libido and ED, and common antidepressant medications, such as selective serotonin reuptake inhibitors, also decrease libido and sexual performance . Knowing the effects on libido and sexual dysfunction, a PDE-5 inhibitor may be necessary to alleviate the sexual symptoms without interfering with depression therapy. The prescribing of PDE-5 inhibitors may allow patients to regain sexual activity and confidence, which can improve depressive symptoms. Subsequently, treatment with a lower dose of selective serotonin reuptake inhibitors may be possible .

Another aspect in treating patients who are HIV positive is the cost of the PDE-5 inhibitors. Because some insurance companies may not cover the cost of these pharmacotherapies, the financial burden of antiretroviral medications and PDE-5 inhibitors may fall primarily on the patient. Patients may opt for surgery, because they know a penile prosthesis is paid for by insurance, whereas the medication may not be . There also may be somewhat of an ethical dilemma in treating HIV-positive patients for ED with either pharmacotherapy or surgery if a male patient does not have a steady committed partner and engages in risky behavior with multiple partners. By treating the ED condition, the physician may feel that he or she is essentially giving the patient a “loaded gun.” A confidential, supportive doctor-patient relationship helps to improve patients’ quality of life while trying to help stop the spread of the virus .

Urologists and other health care professionals who treat ED in HIV-positive patients face a significant challenge in trying to restore normal sexual function. It requires knowledge of the HIV disease and potential drug interactions and learning strategies aimed at reducing the infection rate. This interaction sometimes goes beyond the doctor-patient relationship to include careful consideration of the rights of the partner and society as a whole .

Fertility

With improving life expectancy on HAART, patients present with questions pertaining to fertility and disease transmission. Some patients have abnormal semen parameters associated with atrophy of the testes. Atrophy may be related to hypothalamopituitary axis dysfunction, inflammation, infection, chronicity of the disease, or malnutrition . HIV has its own cytotoxic affect on germinal tissue and Sertoli cells, which leads to testicular atrophy.

Attention and counseling must be given to patients who have HIV and are interested in becoming parents. Transmission rates for unprotected heterosexual intercourse range from 1:1000 per contact (male/female) to less than 1:1000 (female/male) . Options to minimize risk for horizontal and vertical transmission to offspring should be explained. For men infected with the virus, a method described by Semprini and colleagues in 1992, which involves sperm washing followed by assisted reproductive techniques, has proved to be the safest method to date . Tested sperm carry a 10% risk of harboring the virus, which implies that patients are still at risk; in Europe, however, more than 500 children have been born after sperm washing, with zero seroconversions . Mother-to-child transmission—or vertical transmission—can be minimized to less than 2% if cesarean section is performed along with intrapartum infusion of antiviral medications .

Voiding dysfunction

Early data on voiding dysfunction in HIV-positive patients indicated that few patients experienced disturbances in voiding; cases that involved dysfunction were usually associated with UTIs . Patients do present to the primary physician or urologist complaining of lower urinary symptoms, such as dysuria, hesitancy, and decreased stream. Some patients at time of seroconversion experience various neurologic findings, including acute urinary retention. With disease progression patients may experience worsening micturition impairments. Disturbances may be related to recurrent or chronic UTI, central nervous system disturbances (eg, HIV encephalitis, cerebral toxoplasmosis, and HIV-related dementia), or peripheral neurologic deficits . Central and peripheral neurologic causes account for approximately 61% of voiding dysfunction seen in affected patients . AIDS-related malignancies or infectious processes, such as herpes and cytomegalovirus, are a few causes of common lower motor deficits usually seen .

Urodynamics may be useful in identifying underlying dysfunction. Common urodynamic findings identified by Hermieu and colleagues included hypo- and hyperreflexia, acontractile hypoactive bladder, and detrusor-sphincter dyssynergia. Bladder hypocontractility was seen in 35% to 45% of patients at time of urinary retention. Outlet obstruction caused by prostatic enlargement only accounted for 18% of cases in patients with urinary retention. Treatment options for patients with outflow obstruction or hypo- and hyperreflexia can include intermittent catheterization until a patient’s neurologic deficits prevent this task, at which time a chronic catheter or suprapubic cystotomy should be used. Outlet obstruction also can be treated with endoscopic methods when clinically indicated. Bladder hyperreflexia may be treated with anticholinergic agents as first-line therapy. Early reports indicated that patients who experience these abnormalities had a poor prognosis, with mortality usually within a mean of 8 years .

HIV-associated nephropathy

Despite HAART, kidney disease and renal failure are the fourth leading causes of death in HIV-positive patients . Renal failure may be caused by metabolic dysfunction and volume depletion from chronic diarrhea, nephrotoxic medications, infections, ureteral obstruction from malignancies, and intrinsic diseases such as HIV-associated nephropathy. HIV-associated nephropathy occurs more frequently in HIV-positive black patients, with a black-to-white ratio of 12:1. HIV-associated nephropathy has become the third leading cause of end-stage renal disease among black patients aged 20 to 64, after diabetes and hypertension . Characteristics include nephrotic disease with proteinuria more than 3.5 g/d and edema and hypertension. Renal ultrasound evaluation occasionally indicates kidney enlargement, but usually they are within normal size and have increased echogenicity. Diagnosis is confirmed with biopsy. Histologic findings may include a collapsing variant of focal segmental glomerulosclerosis, proliferation of renal tubular and visceral epithelial cells (podocytes), tubular microcystic formation, edema, interstitial fibrosis, and infiltration of the interstitium with leukocytes . Patients progress rapidly, with end-stage renal disease with dialysis requirement occurring within 10 months of diagnosis. Despite hemodialysis, the 1-year-mortality rate is 50%; on antiretroviral therapy it still reaches approximately 30% . Treatment includes HAART therapy for persons not on HIV medications and angiotensin-converting enzyme inhibitors. Medications that depend on renal breakdown and excretion should be adjusted with worsening renal insufficiency and failure.