Acquired immunodeficiency syndrome (AIDS) affects each of the major organs of the genitourinary tract. The predominant aetiological agent, HIV-I, has been cultured from body fluids including blood, urine, pre-ejaculate and vaginal secretions. Thirty per cent of AIDS patients develop significant proteinuria, 50% have pyuria, 18% have haematuria and 50% are hypogonadal.1 Voiding dysfunction and urinary retention may result from an inflammatory, infectious or neurological cause. In addition, weight loss, malnutrition and side-effects of medication may impact on the genitourinary system.1 The incubation period for the development of AIDS following infection with HIV differs between populations, being around 10 years in homosexuals and haemophiliacs, and around 5 years in patients infected via blood transfusions.1 The median incubation period from HIV infection until the development of AIDS is estimated at approximately 10 years in young adults.2 The estimated incubation period varies with the age at which infection occurs, and is significantly shorter in infants and in older adults. It varies even between infection at age 20 years and infection at age 40 years.3
This paper reviews the various organs and areas of the genitourinary tract that are affected by HIV infection and AIDS.
Renal problems that have been associated with AIDS may be classified as functional and structural. AIDS-associated functional problems of the genitourinary tract include the following:1
Hyponatraemia affects 60% of hospitalized patients.1 Volume depletion results from vomiting and chronic diarrhoea. Syndrome of inappropriate antidiuretic hormone hypersecretion is associated with Pneumocystis pneumonia, toxoplasmosis and tuberculosis.1
Hypokalaemia may result from gastrointestinal fluid loss or renal insufficiency due to renal parenchymal disease.1
Acid–base disturbances may be caused by opportunistic infections in the lung and range from respiratory alkalosis to respiratory acidosis.1
Acute renal failure, diagnosed in between 20% and 40% of HIV patients, may also be associated with granulomatous interstitial nephritis.1
Structural renal problems associated with HIV infection include opportunistic infections, tumours and nephropathy. Opportunistic renal infections that may occur are caused by cytomegaloviruses (CMVs),4,5Cryptococcus spp.,4,5Pneumocystis jirovecii,4,5 typical5 and atypical mycobacteria,4Histoplasma spp.,5Candida spp.,5Aspergillus spp.6 and Leishmania spp.7 Kaposi's sarcoma8 and lymphoma9,10 are among the reported tumours associated with HIV. HIV nephropathy (HIVN) is more common in black patients and men.7,11,12 Most cases of HIVN end in end-stage renal disease (ESRD). Peritoneal dialysis is the treatment of choice for HIVN and ESRD. It has been reported that epidemiological data support the use of dialysis in patients with ESRD, as HIV-infected patients requiring either haemodialysis or peritoneal dialysis and receiving highly active antiretroviral therapy (HAART) achieve survival rates comparable to those of dialysis patients without HIV infection.13 It has also been reported that the choice of dialysis modality, between haemodialysis and peritoneal dialysis, is not a factor in predicting survival among HIV-infected patients with ESRD.13
Acquired immunodeficiency syndrome is known to affect both the central nervous system and the peripheral nervous system. Toxoplasmosis is the most common opportunistic infection of the bladder in AIDS patients, and is responsible for neurological disease in up to 15% of patients.1,14 Acute retention of urine is the most common presenting feature.1,15 Urodynamic examination of such patients may reveal areflexia, hyperreflexia or hyporeflexia.1
Human immunodeficiency virus subacute encephalitis may lead to dementia and may worsen voiding dysfunction.1,16 Patients with acute retention of urine occurring as a result of neurogenic disease tend to be unable to empty their bladder without a catheter and urine retention remains.1 After the diagnosis has been established following a neurological examination and urodynamics, the available options include intermittent self-urethral catheterization, insertion of a suprapubic catheter or long-term urethral catheterization.1
Infection with CMV and toxoplasma-induced cystitis may occur in AIDS patients. Kaposi's sarcoma1 and non-Hodgkin's lymphoma of the urinary bladder have also been reported, and these may be complicated by the formation of enterovesical fistulae, which must be treated in AIDS patients who have recurrent urinary tract infections (UTIs) or pneumaturia.1,17 Enterovesical fistulae due to cryptosporidiosis have also been reported in association with AIDS.18
Hoepelman et al.19 reported on 98 HIV-infected men showing symptoms and signs of UTI from whom urine specimens were collected and cultured prospectively at 6-month intervals over a period of 2 years. They found that one or more positive urine cultures were obtained in 30% of patients whose cluster of differentiation (CD) counts were < 200/mm3, and in 11% of patients with CD counts of 200–500/mm3. Hoepelman et al.19 did not find any bacteriuria or symptomatic infective episodes in patients with CD4 counts > 500/mm3. Gugino et al.20 did not find any significant difference between the incidence of bacteriuria in asymptomatic HIV-infected women and HIV-negative female control subjects. A number of authors have stated that asymptomatic bacteriuria is at times detected in HIV-infected patients; however, only symptomatic patients need treatment with culture-specific antibiotics.21–23 Some authors have stated that in addition to the common uropathogens, such as Escherichia coli and Klebsiella spp., organisms such as Staphylococcus aureus, Pseudomonas spp. and Enterococcus spp. are often cultured.22,23 Evans et al.24 and Van Dooyeweert et al.25 reported that the widespread use of cotrimoxazole prophylaxis to prevent P. jirovecii infection in patients suffering from AIDS has led to a reduction in the incidence of bacterial infections, including those of the urinary tract; however, UTIs caused by organisms that are resistant to cotrimoxazole can develop nonetheless.
It has been stated that the antibacterial protection offered by zinc, spermine and spermidine in the prostate falls as HIV infection progresses.26,27 Le Port et al.27 observed that whereas the incidence of bacterial prostatitis in the general population has been estimated at 1–2%, this rises to 3% in asymptomatic HIV-positive patients and to 14% in patients with AIDS.
Staiman and Lowe28 asserted that prostatitis ensues from an ascending urethral infection, by direct invasion of the rectal bacteria or as a result of haematogenous spread to the prostate. They noted that prostatitis usually manifests acutely with severe irritative urinary symptoms, fever and malaise, and on rectal examination the prostate is found to be swollen and very tender.
Staiman and Lowe28 suggested that in the HIV-infected patient, the treatment of prostatitis must be culture specific and, in view of a high risk of reinfection as well as lowered immunity, the partners of HIV-infected patients and patients with AIDS should also be treated. They recommended the use of fluoroquinolones, such as 500 mg ciprofloxacin or 400 mg norfloxacin, twice per day for 4 weeks as the first-line course of treatment, to build up good therapeutic levels of fluoroquinolones in the prostate gland. Staiman and Lowe28 stated that common pathogens encountered in prostatitis in HIV-infected and AIDS patients include E. coli and Proteus spp., with atypical pathogens including Salmonella Typhi, Pseudomonas aeruginosa and Neisseria gonorrhoeae responsible in some cases.
A number of AIDS patients develop opportunistic infections of the prostate gland. Patients with AIDS-associated opportunistic infections of the prostate tend to develop fever and voiding symptoms, and other symptoms of a UTI. Rectal examination of these patients usually reveals a tender prostate, which may be soft or fluctuant. The latter is suggestive of an abscess.
Other common causes of bacterial prostatitis in AIDS include E. coli,29Haemophilus influenzae,30 klebsiellae,1,29Mycobacterium avium,31 Mycobacterium tuberculosis,31–37Pseudomonas spp.,1Salmonella spp.38 and S. aureus.31,39 Fungi which have been found in AIDS-associated prostatitis include Cryptococcus spp.,40–42 species of the phylum Microsporidia,43Aspergillus spp.44 and Histoplasma spp.1,45 Viruses associated with prostatitis in AIDS include CMV and HIV,46 as well as adenovirus.47 It has been stated that the incidence of prostatitis is higher in HIV-infected patients, with an increased risk of abscess formation.48
Treatment of prostatic abscesses in such situations may require transurethral drainage/de-roofing, with intraoperative collection of pus for cultures of aerobes, anaerobes, fungi and mycobacteria.26,31,49 In HIV-positive patients there is a greater likelihood of finding atypical pathogens, including fungi, tuberculosis, anaerobes and viruses. As these patients are at greater risk of developing prostatic abscesses and urosepsis than the general population, increased monitoring and evaluation and longer-term, appropriately directed, antimicrobial therapy are required.50
It has been reported that carcinoma of the prostate progresses faster in HIV-infected patients than in other patients. However, Wosnitzer and Lowe51 noted that in the era of HAART, evidence indicates that prostate-specific antigen kinetics and prostate cancer behaviour are similar in HIV-positive and HIV-negative patients.51 Wunder et al. 52 observed that HIV-infected patients are often hypogonadal and do not readily respond to hormone treatment. Their data showed that a considerable proportion of treatment-naive HIV-positive men have abnormally low age-adjusted levels of free testosterone (FT), which is not reversible after 2 years of successful combined antiretroviral therapy. This deficiency may have an impact on psychological issues such as depression, fatigue, lack of drive and decreased libido, but may also have long-term consequences including osteoporosis, loss of weight and anaemia. The authors suggested that these patients should be checked for hypogonadism, with testosterone supplementation provided if necessary once contraindications are excluded.
Kaposi's sarcoma is the most commonly reported malignancy associated with AIDS and one of the earliest manifestations of HIV infection.53 Kaposi's sarcoma of the penis presents as nodules and plaques on the penis, lymph node and visceral involvement and lymphoedema. It has been stated that 20% of Kaposi's sarcomas are associated with genital lesions. Kaposi's sarcoma of the penis manifests as a purplish-red lesion. Kaposi's sarcomas that manifest as solitary lesions can be treated adequately by means of local excision or fulguration. Larger, multifocal lesions of the penis most often require radiotherapy. In cases of periurethral Kaposi's sarcoma, such lesions can cause urethral obstruction, such that urethral dilatation or insertion of a suprapubic catheter may become necessary. Squamous cell carcinoma of the penis has also been reported in HIV-infected patients. Heyns et al.29 stated that, for patients who do not have access to HAART, HIV infection continues to be a lethal disorder characterized by opportunistic infections with uncommon organisms (e.g. mycobacteria, fungi, parasites and viruses), as well as lethal malignancies such as Kaposi's sarcoma, non-Hodgkin's lymphoma and squamous cell carcinomas of the penis and cervix.29
Urethritis caused by Chlamydia trachomatis and N. gonorrhoeae presents in the HIV-positive patient (as in the general population) with dysuria with or without urethral discharge, which may be purulent and profuse or minimal.26
For the diagnosis of urethritis, a first-void specimen of urine is collected and intraurethral swabs (from within 1 cm of the external urethral meatus for gonorrhoea and 4 cm of the external urethral meatus for chlamydia) are taken 1–4 hours after voiding. 26 According to Granato et al.,54 urethritis is diagnosed if five white blood cells (WBCs) per oil-immersion field are detected on the Gram staining of urethral secretions, or if there are 10 WBCs per high-power field on the first-void specimen of urine. They also stated that gonococcal urethritis can be established with approximately 99% specificity and 95% sensitivity by the detection of WBCs containing Gram-negative diplococci. Schepetiuk et al.55 reported that commercially available kits now exist which can be used to detect Chlamydia nucleic acids by means of polymerase chain reaction, with > 95% sensitivity and specificity.
Guidelines for the treatment of sexually transmitted disease, published in 1998 by the Centers for Disease Control and Prevention,56 stipulate that pharyngeal and rectal specimens should be collected where there is a history of oral genital contact or anal intercourse. HIV-infected patients should be treated presumptively for both chlamydia and gonorrhoea if gonococci are isolated, as concomitant infection is found in 30–50% of cases.
According to Stamm et al.57 and the 1998 guidelines,56 treatment options in the case of gonococcal urethritis include a single dose of 500 mg oral ciprofloxacin (99.8% of cases are cured), a single dose of oral cefixime (97% of cases are cured) or a single dose of oral ofloxacin (98% of cases are cured). The guidelines also suggest that, in view of the increased viral shedding with genital infections, HIV-infected patients are advised to abstain from sexual intercourse until 7 days after the commencement or completion of their treatment.
It has been stated that symptoms of urinary frequency and dysuria develop secondarily to CMV metabolite-induced damage or HIV activation.1 It has also been observed that Reiter's syndrome may be associated with AIDS. In view of this, HIV testing is recommended in new patients with Reiter's syndrome who have risk factors for HIV infection. Cases of primary T-cell lymphoma and B-cell lymphoma of the urethra have also been linked with HIV infection and AIDS.1
A number of cases of testicular atrophy have been reported in AIDS patients, and these have been attributed to prolonged febrile state, testicular infection and secondary dysfunction from hypothalamic–pituitary disease.1 Mhawech et al.58 carried out a retrospective study of risk factors in HIV-infected men to investigate the relationship between complications of AIDS, such as wasting or opportunistic illness, and testicular atrophy. They evaluated microscopic sections of the right testis for testicular atrophy, by assessing the mean score in each of 80 selected HIV-infected patients who underwent an autopsy during a 1-year period. Mhawech et al.58 observed a significant association between testicular atrophy and body mass index (P = 0.0496). They concluded that underweight patients with HIV infection were more likely to have testicular atrophy than those with acceptable body weight. No significant associations with other variables were found.
Human immunodeficiency virus-infected patients are often hypogonadal and do not readily respond to hormone treatment.1 Organisms causing opportunistic infections of the testis which have been reported in HIV-positive patients include CMVs, Candida spp. and Toxoplasma1In addition, a 0.2% incidence of germ cell and non-germ cell tumours of the testis has been recorded in HIV-infected patients – 50 times greater than that seen in the general population. It has been recommended that HIV-infected patients should receive standard treatment; however, there are problems with AIDS patients tolerating chemotherapy and surgery.1
In young men, epididymitis is commonly caused by the spread of infection from the urethra, with N. gonorrhoeae and C. trachomatis being the two most commonly encountered organisms. Some authors have reported that unprotected anal intercourse has resulted in the development of epididymitis caused by coliform organisms in a number of homosexual men.59–61 The Centers for Disease Control and Prevention's 1998 guidelines for the treatment of sexually transmitted diseases56 recommend 100 mg oral doxycycline twice per day and 500 mg oral ciprofloxacin twice per day for 2–4 weeks in such cases. This should be adequate to treat most of the common pathogens.
According to Parr et al.,62 a previously undiagnosed HIV infection may manifest for the first time as suppurative and/or antibiotic-resistant epididymitis. Desmond et al.63 found that fungi or mycobacteria may be the cause of epididymitis in an HIV-seropositive male. Opportunistic organisms that have been reported to cause epididymitis in HIV patients include Salmonella spp., which are quite difficult to eradicate, and Salmonella infection may necessitate lifelong maintenance antibiotic therapy.1 Obstructive epididymitis can occur in HIV-infected patients as a result of CMV inclusion bodies and Kaposi's sarcoma cells.1
Cellulitis of the scrotum has been associated with HIV infection.64 Cases of Fournier's gangrene have also been reported in HIV-infected patients. The causative pathogens of Fournier's gangrene in these patients are quite often atypical.1
Renal colic and ureteric obstruction have been reported in AIDS patients on antiretroviral treatment.65
Genital ulcers in HIV-positive patients may be caused by the sexually transmitted diseases chancroid, genital herpes and syphilis. Rarely, genital ulceration may result from contact with an antiviral therapeutic agent, foscarnet, which is excreted via the urine. Genital ulceration may also be a manifestation of systemic illness due to CMV or herpes zoster.26
Treponema pallidum, a spirochaete, causes the syphilitic infection which manifests as a chancre or ulcer at the site of infection. Methods of establishing an early diagnosis of syphilis include dark-field examination and direct fluorescent antibody tests of exudates from the lesion or tissue. Erbelding et al.66 showed that the fluorescent treponemal antibody-absorbed test has a tendency to produce false-negative results and a delayed appearance of seroreactivity. In view of this, the test may not be reliable for use in HIV-infected patients. The 1999 UK national guidelines on sexually transmitted disease and closely related conditions67 state that HIV-infected patients are more likely to develop neurological complications (which are associated with a higher treatment failure) early in the disease. In view of this it has been recommended that, after treatment with 2.4 MIU intramuscular daily injections of procaine penicillin, plus 500 mg probenecid four times daily for 21 days, HIV-positive patients should be assessed clinically and serologically for treatment failure at 3, 6, 9 and 12 months. The guidelines also recommend that patients with penicillin allergy should be given 200 mg doxycycline four times daily for 21 days, even though side-effects such as nausea and vomiting are quite common with high-dose doxycycline.
Some authors68,69 have reported that genital herpes is an incurable, recurrent viral disease which is caused by herpes simplex virus II (HSV-II) and less commonly by herpes simplex virus I (HSV-I). They observed that episodes of the infection may tend to become more severe and prolonged as HSV progresses. When the lesions or ulcers persist beyond 1 month, the patient is classified as having AIDS-defining illness.
Safrin et al.70 found that direct fluorescent antibody stain (Tzanck smear) or a viral swab or scraping from the base of an intact blister differentiates HSV infection from CMV infection. They noted that serological testing for HSV infection is not helpful in view of the high prevalence of HSV-I and -II in the general population as well as in the HIV-infected population.
Scoular and Barton71 suggested that HIV-infected patients with HSV infections should be treated with higher than standard doses of oral acyclovir (400 mg 3–5 times per day) until the symptoms clear. They also stated that patients with AIDS and acyclovir-resistant HSV infection should be treated with intravenous foscarnet.
The Centers for Disease Control and Prevention's 1998 guidelines highlight that twice-daily suppressive therapy with 500 mg famciclovir is effective in reducing recurrent episodes and subclinical viral shedding in HIV-infected patients.56
Non-ulcerating genital sexually transmitted diseases
Some authors72,73 have affirmed that the incidence of mucosal candidiasis in human immunodeficiency syndrome is related to the degree or extent of the immunodeficiency. They also state that balanitis due to Candida spp. is not common; however, around 75% of HIV-infected women develop at least one episode of candidiasis of the vulva and vagina, and this quite often precedes oral candidiasis. Quite often the diagnosis of candidiasis is based upon clinical appearance of the lesion. However, the diagnosis may be confirmed by the identification of pseudohyphae or yeasts on a wet mount with 10% potassium hydroxide preparation.26 The Centers for Disease Control and Prevention's 1998 guidelines56 indicate that application of a topical antifungal (miconazole, clotrimazole or tioconazole cream or pessary) for 7–10 days, or 150 mg oral fluconazole as a single dose, is effective in the treatment of candidiasis in the HIV-infected patient.
In 90% of cases of condyloma acuminata (genital warts), human papillomavirus (HPV) type 6 or 11 is the aetiological agent. Studies have shown that genital warts are found in 20% of HIV-infected patients, compared with 0.1% of the general population.69,74 HPV types 16, 18, 31, 33 and 35 occasionally cause anogenital warts, and have been strongly associated with cervical dysplasia and external genital squamous intraepithelial neoplasia such as Bowenoid papulosis, erythroplasia of Queyrat and Bowen's disease. 26
The Centers for Disease Control and Prevention guidelines56 recommend that treatment of small areas of genital warts may be ‘patient-administered’ with topical 0.5% podophyllin fluid, 0.15% podophyllin cream or imiquimod 5% cream, or in a genitourinary clinic with 10–25% podophyllin, 80–90% trichloroacetic acid or cryotherapy. With regard to further management, the guidelines advise that a biopsy should be performed if the lesions worsen or do not respond to treatment.26,56 In addition, it has been recommended that extensive areas of genital warts may require surgical excision. Vaporization using a carbon dioxide laser should not be performed because of dispersion of oncogenic viruses in the aerosol.26
Cutaneous drug eruptions
Some authors have stated that, in view of the altered cellular immunity that HIV-infected patients develop, such patients become susceptible to cutaneous drug hypersensitivity eruptions.68,69,75 Cotrimoxazole induces a morbilliform cutaneous eruption of erythematous papules and macules on the trunk and extremities, including the genitalia.26 Stevens–Johnson syndrome, an allergic reaction which manifests with fever and widespread blisters of the mucous membranes of the mouth, eyes and genitalia as well as blisters of the skin, may complicate the use of cotrimoxazole.26
As the use of the antiviral agent foscarnet may be complicated by contact ulcerations of the genitalia, Lee et al.26 recommended that patients on foscarnet should be advised to wash thoroughly after voiding.
Biggar and Rabkin76 showed that Kaposi's sarcoma is 7000 times more common in HIV-infected individuals than in the uninfected population, and homosexual men are at the highest risk of developing this disease. A number of authors77,78 have postulated that the interaction between Kaposi's sarcoma-associated herpes virus and various human cytokines results in the development of Kaposi's sarcoma.
Lowe et al.79 noted that Kaposi's sarcoma can affect any organ in the body, including the brain, liver, mucous membrane and skin, but it is not usually fatal. They described the appearance of the disease in the form of painful papules which tend to affect surfaces that undergo trauma. In 20% of patients this involves the genitalia; however, the initial lesion affects the penis in < 3% of cases.
Tappero et al.80 described confirmation of the diagnosis of Kaposi's sarcoma by means of histological examination. They also indicated that the appearance of a new Kaposi's sarcoma could imply inadequate suppression of viral replication. In view of this, treatment of this disease will be best achieved through improvement of the antiviral treatment which would eradicate the Kaposi's sarcoma lesions. The authors posited that persistent small lesions of Kaposi's sarcoma on the genitalia would be best treated using cryotherapy.80 Others have recommended that larger areas of persistent lesions should be treated with radiotherapy.81,82
A number of studies83–85 have reported that the incidence of non-Hodgkin's lymphoma is approximately 60 times greater in HIV-infected individuals than in uninfected individuals. The incidence rises sharply when the CD4 count falls to < 50/mm3. Seney et al.86 found renal lymphomas in 2% of autopsies carried out on AIDS patients. Crellin et al.87 confirmed that primary non-Hodgkin's lymphoma of the testis is more common and more aggressive in HIV-positive men than in the general population, and is also more likely to be bilateral. Reports by Mohler et al.88 and Cespedes et al.89 recommended that orchidectomy of the affected testis should be performed in order to avoid relapse. They also stated that retroperitoneal non-Hodgkin's lymphoma may present with obstructive uropathy, which would necessitate the creation of nephrostomies. It has been noted90,91 that as HIV-infected patients usually present with more advanced and histologically high-grade disease, and owing to their lack of anti-tumour immunity, treatment of non-Hodgkin's lymphoma by means of standard chemotherapy results in a higher relapse rate in these patients.
Germ cell tumours of the testes have been found to be 50 times more common in HIV-positive men than in the general population, with 2 new cases per 1000 HIV-infected patients compared with 3.5 new cases per 100 000 of the general male population.92–94 These tumours tend to be more aggressive in HIV-infected men, and often develop in the testes bilaterally. Reports examining whether seminomas or teratomas are more predominant are conflicting.93,94
Leibovitch et al.94 described the treatment of HIV-positive patients with germ cell tumours of the testes using radiotherapy or platinum-based chemotherapy, depending upon the histological appearance and stage of the tumours. Morbidity and response are comparable to those seen in non-immunosuppressed patients. The authors noted that AIDS patients who have previously undergone bone marrow suppression using drugs, and who have low leucocyte counts or severely depressed immunity (for example, those patients with low CD4 count), are unable to tolerate standard treatment regimens well and have a poor prognosis.94 They recommended that treatment of germ cell tumours of the testes in AIDS patients should be individualized, taking into account concurrent illnesses that the patient may have.
Other malignancies of the genitourinary tract may also afflict the HIV-infected patient. For example, Wang et al.95 found that carcinoma in situ (Bowen's disease) of the penile skin and labia is commonly found in these patients. Gerber96 and Harth et al.97 stated that squamous cell carcinoma and giant verrucous carcinoma assume a more aggressive course in the HIV-positive patient. They reported that carcinoma in situ has been successfully treated by means of cryotherapy, topical 5-fluorouracil, surgical excision or photodynamic therapy. Squamous cell carcinoma should be treated aggressively by means of radical excision or radiotherapy.
Eghafona and Omoregie99 studied the impact of HIV infection and CD4 count on the prevalence of UTI. They collected clean-catch mid-stream specimens of urine and venous blood from 421 subjects, 317 HIV-infected patients (89 men and 228 women) and 104 individuals without HIV (48 men and 56 women). The HIV-infected subjects comprised 101 HAART-naive patients and 216 patients who had received HAART for 3–6 months. All HIV-infected patients were asymptomatic, with no signs or symptoms of UTI. Microbial isolates were identified in urine and susceptibility tests were performed. Only HIV-infected patients who were on HAART had a significantly higher prevalence of asymptomatic UTI in comparison with uninfected individuals [prevalence 27.78% vs. 17.315%; OR 1.8376; 95% confidence interval (CI) 1.0198–3.3112; P = 0.0411]. This study found that:
Among both the HAART-naive and the receiving HAART groups, CD4 count < 200 cells/mm3 was not associated with asymptomatic UTI.
S. aureus was the most common uropathogen (found in 27.2% of people who had asymptomatic UTI) and nitrofurantoin was the most active antibacterial agent.
Most bacterial isolates were resistant to other antibacterial agents used (amoxicillin, amoxicillin clavulanate, gentamicin, cotrimoxazole, tetracycline, nalidixic acid, ciprofloxacin and ofloxacin).
Overall prevalence of asymptomatic UTI was 24.94%.
HIV patients on HAART had a one- to threefold higher risk of acquiring UTI compared with patients without HIV.
CD4 count was not associated with asymptomatic UTI.
The aetiological agents of UTI which have been reported in HIV-infected subjects include E. coli, S. aureus, Klebsiella spp., P. aeruginosa, Proteus spp. and Staphylococcus epidermidis.100 Heyns et al.29 listed E. coli, S. aureus, Klebsiella pneumoniae, P. aeruginosa, Acinetobacter spp. and Proteus spp. as common causes of UTI in AIDS.
Breyer et al.101 performed a cross-sectional, internet-based survey of urinary quality of life outcomes in adult HIV-infected and uninfected men who had sex with other men. The main outcome recorded for each respondent was the International Prostate Symptom Score. The authors reported the following findings:
Of respondents for whom complete data were available, 1507 were HIV uninfected (median age 42 years, mean age 43 years) and 323 were HIV infected (median age 45 years, mean age 45.1 years).
Of the HIV-infected respondents, 148 had non-AIDS-defining and 175 had AIDS-defining infection.
After adjusting for age and other comorbid conditions, non-AIDS-defining and AIDS-defining HIV infection increased the odds of severe lower urinary tract symptoms by 2.07 (95% CI 1.04–3.79) and 2.49 (95% CI 1.43–4.33), respectively.
HIV-infected men had lower total International Prostate Symptom Scores for all domains, including quality of life, than HIV-uninfected men.
Within the population of men with HIV infection, those with AIDS had lower mean total International Prostate Symptom Scores, and lower scores for all individual components, than non-AIDS-defining infected men.
Breyer et al.101 concluded that HIV infection status is an independent risk factor for bothersome lower urinary tract symptoms, and that the odds of severe lower urinary tract symptoms are greater in HIV-infected men with a history of AIDS.
Gaughan et al.102 stated that chronic HIV infection is associated with an increased incidence of non-AIDS-defining cancers. They also observed that only a limited number of bladder cancer cases had been linked with HIV infection, and sought to describe the clinical characteristics of HIV-associated bladder cancer. To this end the authors conducted a retrospective study involving HIV-positive patients with bladder cancer. They combined cases from multiple institutions with published case reports, and analysed data regarding patient demographics, HIV infection status, clinical presentation, pathology, cancer treatment and outcome using descriptive statistics. Gaughan et al.102 reported that they identified a total of 11 patients with a median age of 55 years (range 33–67 years). The median CD4+ count at the time of diagnosis with cancer was 280 cells/mm3 (range 106–572 cells/mm3). Six patients (55%) had a known risk factor for bladder cancer. Nine (82%) presented with haematuria. Ten patients had transitional cell carcinoma, and most had superficial disease at presentation. The treatment received comprised in most cases a transurethral resection of the bladder tumour followed by a combination of local and systemic therapies. One patient received intravesical bacillus Calmette–Guerin without complication. Around half (55%) of patients were still alive following therapy, although many (64%) of these suffered local relapse and metastatic disease. Gaughan et al.102 concluded that bladder cancer is part of the growing list of cancers that may be encountered in patients living longer with chronic HIV infection. The patients presented at a younger age and with only mild immunosuppression; however, the bladder cancer that they experienced followed an expected course. The authors specified that haematuria in an HIV-infected patient warrants a complete evaluation.
Ferron et al.103 reported four cases of bladder cancer in an ethnically diverse population of around 2500 HIV-infected patients. These patients were younger than the median age at which bladder cancer is diagnosed in the USA. At the time of cancer diagnosis, their CD4+ cell counts ranged from 88/μl to 305/μl. Two patients had low-grade papillary carcinoma at diagnosis, one with muscle invasion and the other with progression from low-grade metastatic bladder cancer. One patient with a low-grade tumour did not have disease progression after the first relapse, and one patient had high-grade stage IV cancer at diagnosis.
Skoutelis et al.104 reported two cases of tuberculous epididymitis with serious complications (bilateral psoas abscesses and Addison's disease with psoas abscesses). They reviewed the literature and found six additional cases with serious complications (Addison's disease, inappropriate antidiuretic hormone secretion and central nervous system involvement) which were discussed and compared with their cases. They concluded that tuberculous epididymitis represents a grave sequela of genital tract involvement and may be associated with serious and even fatal complications.
Schmid et al.105 performed a retrospective analysis of the kidney biopsies of 30 HIV-positive patients. Twenty-two of the patients received HAART. HAART comprising tenofovir together with atazanavir, a new protease inhibitor, was administered to three patients. All of them developed acute renal failure. The kidney biopsies of these patients showed acute interstitial nephritis, or chronic interstitial nephritis with an acute component. They observed that withdrawal of atazanavir and tenofovir resulted in recovery of renal function in all three patients. Acute interstitial nephritis was seen in only 1 of 19 patients who did not receive atazanavir or tenofovir treatment. The authors concluded that acute interstitial nephritis followed by acute renal failure is a relevant side-effect of atazanavir and tenofovir therapy in HIV-positive patients.
Fernando et al.106 noted that the prevalence of chronic kidney disease (CKD) in the HIV-infected population during the HAART era has not been fully evaluated. To determine the prevalence of CKD, they conducted a retrospective chart review of HIV-infected patients who were examined in 2004, using the 2004 National Kidney Foundation's CKD staging criteria.106 Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Univariate analyses were performed comparing individuals with normal kidney function with those with CKD. Multivariate analysis was conducted including all variables with a value of P < 0.1. Fernando et al.106 found evidence of CKD in 24% of the patients. Forty of these (10% of all patients) had stage 1, 19 (4%) had stage 2, 29 (7%) had stage 3, four (1%) had stage 4, and eight (2%) had stage 5 CKD. They also reported that:
Patients with CKD were more likely to be African American, older, and to have AIDS, lower CD4 counts and higher HIV viral loads.
Patients with CKD were also more likely to have hypertension, diabetes mellitus or both.
Indinavir or tenofovir exposure was associated with CKD.
In a multivariate analysis, hypertension, African American race or a combination of hypertension and diabetes mellitus were the only significant predictors of CKD.
Physicians failed to identify CKD in 74% of affected patients.
Renal biopsies were performed in 10 patients; five had HIVN.
Fernando et al.106 concluded that substantial minorities of HIV-infected patients have CKD. African American race and the presence of hypertension, or hypertension and diabetes together, are associated with CKD. Clinicians often overlook the presence of CKD in this population.
Mocroft et al.107 reported that CKD in HIV-positive patients can be caused by both HIV-related and non-HIV-related factors. They conducted a study to investigate the relationship between long-term exposure to specific antiretroviral drugs and CKD. This included 6843 HIV-positive participants with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. Mocroft et al.107 defined CKD, using the Cockcroft–Gault formula, as a confirmed (two measurements ≥ 3 months apart) estimated glomerular filtration rate (eGFR) of ≤ 60 ml/min per 1.7 m2 for persons with a baseline eGFR of > 60 ml/min per 1.73 m2. Poisson regression was used to determine factors associated with CKD. Two hundred and twenty-five participants (3.3% of the total) progressed to CKD during 21 482 person-years of follow-up, an incidence of 1.05 per 100 person-years of follow-up (95% CI 0.91–1.18). Median follow-up was 3.7 years (interquartile range 2.8–5.7 years). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16; 95% CI 1.06–1.25; P < 0.0001], indinavir (IRR 1.12; 95% CI 1.06–1.18; P < 0.0001), atazanavir (IRR 1.21; 95% CI 1.09–1.34; P = 0.0003) and lopinavir (IRR 1.08; 95% CI 1.01–1.16; P = 0.030) was associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although these were of marginal statistical significance in the case of lopinavir. No other retroviral drugs were associated with increased incidence of CKD. The authors concluded that, in this non-randomized, large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD. The same was true for indinavir, although the results for lopinavir were less clear.
Gyrtrup et al.108 prospectively investigated the prevalence and types of urinary voiding problems in 77 men and four women (median age 36 years) with HIV infection or AIDS, who consecutively attended their outpatient clinic. Urologic symptoms were registered based on responses to a questionnaire, and urologic evaluation was made when indicated by the results of the questionnaire. All patients were neurologically examined. In addition, the authors retrospectively analysed urodynamic data from 10 consecutively referred HIV-infected and AIDS patients. Of the 81 patients who were prospectively studied, two had severe and eight had moderate voiding problems. Nineteen had pathological findings at neurological examination. Of three patients who were referred for urodynamics, two were found to have neurogenic bladder dysfunction. Of the total 13 patients studied for urodynamics, findings in three suggested neurogenic bladder dysfunction secondary to the infection. The conclusion drawn was that HIV infection and AIDS affect voiding to only a minor degree, and when they do, the disease is often advanced and dominated by symptoms from other organs. The relevance of urological and urodynamic investigations in HIV-infected and AIDS patients thus seems limited.
Moriyama et al.109 reported on a 51-year-old HIV-positive man who presented with anuria following right flank pain. He had been treated with atazanavir for 9 months. A computed tomography (CT) scan of the abdomen and pelvis showed bilateral hydroureteronephrosis, but no stones were visualized. The patient underwent cystoscopy and retrograde studies, which revealed a yellowish stone composed of pure atazanavir at the right ureteric orifice. A retrograde ureteropyelogram revealed a filling defect in the left ureter, which was found to be caused by an atazanavir stone. The patient's renal function recovered after the stones were removed.
In 2008, Feicke et al.110 reported the first case to lead to amprenavir being added to the growing list of drugs associated with urinary stones. They stated that the first reported case of a nelfinavir urinary stone was reported in 2002, in a 37-year-old HIV-infected woman. In September 2007, the same female patient was referred to their department with recent onset of right flank pain and recurrent urinary tract infections. CT of her abdomen and pelvis showed three obstructing stones in the distal right ureter, another stone in the right renal pelvis with hydronephrosis and a stone in the left kidney. Following stone retrieval, analysis of the stone was performed by liquid chromatography with mass spectrometry, which revealed a stone composition of 95% unmodified amprenavir and 5% ritonavir.
Brandenburg et al.111 described three HIV-seropositive patients who were diagnosed with urolithiasis related to the use of indinavir. The first patient was a 45-year-old white man with severe haemophilia who presented with flank pain which was referred to the glans penis and was associated with fever. Ultrasonography of the renal tract and intravenous pyelography revealed a concrement in the left renal pelvis. Discontinuation of indinavir and acidification of the urine did not reduce the stone load. Percutaneous nephrolithotripsy was then performed. The second patient was a 41-year-old white man who presented with fever and flank pain. An ultrasound scan of the renal tract showed left hydronephrosis. A percutaneous nephrostomy was inserted. A nephrostogram showed a concrement in the proximal ureter. The patient underwent extracorporeal shock wave lithotripsy, after which nephrostography showed complete clearance of the stone. The third patient was a 56-year-old white man with a history of indinavir-associated urolithiasis. He presented with flank pain and haematuria. CT urography showed right hydroureteronephrosis with no evidence of a stone or concrement. His symptoms subsided after insertion of a percutaneous nephrostomy, and the antiviral medication was modified. The nephrostomy was removed 2 weeks later. Brandenburg et al.111 reported that at the last follow-up none of the three patients had symptoms of urolithiasis. They noted that these cases illustrate that, although conservative therapy for indinavir-related urolithiasis can be sufficient, minimally invasive endourological surgery is sometimes necessary.
Moreno Pérez et al.112 aimed to determine the incidence of erectile dysfunction in a cohort of HIV-infected men in a stable clinical state, as well as examining the effect of antiretroviral therapy on sexual dysfunction and identifying the risk factors. In this study, HIV-infected men without hepatitis C co-infection were included if they were antiretroviral therapy naive (naive group), on current treatment with an enhanced protease inhibitor (protease inhibitor group) or on current treatment with a protease inhibitor (non-nucleoside reverse transcriptase inhibitor group). Erectile dysfunction was defined as an ejection fraction of 25 or less (International Index of Erectile Function 15). The authors reported that 90 patients were included, with an age of 42 ± 8.2 years and CD4 count of 465/μl (interquartile range 361–676/μl). Of these, 18.9% were in the Centers for Disease Control and Prevention class C, and 72.2% had an undetectable viral load. Seventy-six patients (84.4%) were receiving antiretroviral therapy, 39 (43.3%) of whom were in the protease inhibitor group. The prevalence of lipodystrophy was 31.5%. Forty-seven patients (53.4%) had erectile dysfunction. Multivariate logistic regression analysis confirmed that there was an independent association between the patients' age (per decade; odds ratio 2.2; 95% CI 1.04–4.5; P = 0.04) and greater duration of exposure to protease inhibitor (per year; odds ratio 1.6; 95% CI 1.12–2.4; P = 0.01). Older age, depression and lipodystrophy, combined with the duration of exposure to protease inhibitor, determined a lower score on various sexual dysfunction domains (P< 0.05). The authors concluded that there is a high prevalence of erectile dysfunction in HIV-infected men, with age and duration of exposure to protease inhibitor being the only identifiable risk factors.
Kong and Edmonds113 stated that many HIV-infected patients lose weight, which increases morbidity and mortality. They assessed the effects of testosterone therapy on lean body mass, total body weight, overall functional capacity for exercise and perceived quality of life in patients with HIV wasting syndrome and its adverse effects. They systematically reviewed randomized, placebo-controlled trials that compared the effects of testosterone therapy with placebo in HIV-infected patients with wasting. They reported that eight trials met the inclusion criteria and 417 patients were included. Only six trials used lean body mass, fat-free mass or body cell mass as outcome measures. The meta-analysis of the six trials showed a difference in the lean body mass between the testosterone group and placebo group of 1.22 kg (95% CI 0.23–2.22 kg) for the random effect model and 0.51 kg (95% CI 0.09–0.93 kg) for the fixed effect model. Nevertheless, the difference was much greater in the three trials that used the intramuscular route: 3.34 kg in the post-hoc analysis. All eight trials included total body weight as an outcome measure, the meta-analysis of which suggested a difference of 1.04 kg (95% CI −0.01 to 2.10 kg) between the testosterone group and the placebo group for the random effect model and 0.63 kg (95% CI −0.01 to 1.28 kg) for the fixed effect model. Overall, the incidence of adverse effects was similar in both groups. Testosterone therapy was shown in the review to increase lean body mass more than placebo. The increase was even greater if the therapy was given intramuscularly. There was also a small positive effect on the total body weight. Kong and Edmonds113 commented that the study was limited, however, in view of the small numbers and heterogeneity of the population studied, which in their opinion could potentially have introduced bias into the methods and the results. Kong and Edmonds113 concluded that testosterone therapy may be considered in patients with HIV wasting syndrome to reverse muscle loss; however, there is concern about the adverse metabolic effects of long-term testosterone administration, and long-term follow-up is required for these patients.
Fairfield et al.114 stated that:
Multiple endocrine and metabolic sequelae of HIV infection exist that may contribute to bone loss in men with the AIDS wasting syndrome.
Studies prior to that conducted by Fairfield et al.114 suggested that anabolic strategies can increase lean body mass in men with AIDS wasting.
These studies had not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men.
To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, Fairfield et al.114 randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% of ideal body weight or weight loss > 10% from pre-illness baseline) to receive either testosterone enanthate (200 mg/week, intramuscularly) or placebo, and to undertake progressive resistance training (three times per week) or no training, in a 2 × 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur and total body, lean body mass and fat mass were measured by dual-energy X-ray absorptiometry. Total body scans were repeated after weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy, non-HIV-infected control subjects. In comparison with the control subjects, lumbar spine BMD (1.021 ± 0.018 vs. 1.084 ± 0.025 g/cm2; P = 0.05) and total hip BMD (0.65 ± 0.11 vs. +0.20 ± 0.014 g/cm2; P < 0.0001) were reduced in men with AIDS wasting. T-scores – which provide a measure of BMD as the number of standard deviations from the young adult mean – were lower in men with AIDS wasting. Fairfield et al.114 found that neither the use of protease inhibitors nor the duration of their use correlated with BMD. Serum osteocalcin levels were found to be lower (3.63 ± 0.29 vs. 4.54 ± 0.31 nmol/l; P < 0.04) and urinary N-telopeptide excretion was higher [45.4 ± 4.5 vs. 26.8 ± 3.0 nmol bone collagen equivalent (BCE)/mmol creatinine; P = 0.0004] in men with AIDS wasting than in control subjects. Lumbar spine BMD, assessed by means of a regional total-body dual-energy X-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 1.3 vs. 1.3 ± 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (0.8 ± 1.0 vs. +0.4 ± 1.3%, training vs. no training; P = 0.70). Fairfield et al.114 concluded that:
Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting.
Biochemical markers of bone turnover suggest that bone formation and bone resorption are encountered in these men.
Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.
Rabkin et al.115 evaluated the efficacy of testosterone in the alleviation of hypogonadal symptoms (diminished libido, depressed mood, low energy and depleted muscle mass) in men infected with HIV. The authors enrolled patients in a double-blind, placebo-controlled 6-week trial of biweekly testosterone injections, followed by 12 weeks of open-label maintenance treatment. Major outcome measures that were assessed include:
Clinical Global Impressions Scale ratings for libido, mood, energy and erectile function;
Hamilton Depression Ratings Scale scores;
Chalder Fatigue Scale scores;
bioelectric impedance analysis for body composition changes.
Seventy men completed the 6-week trial. The authors reported the following findings:
Response rate, defined as much or very much improved libido, was 74% (28 of 38 patients) among patients who were randomized to testosterone and 19% (6 of 32 patients) among those who received the placebo (P < 0.001).
Among the 62 patients with fatigue at baseline, 59% of those receiving testosterone (20 of 34) and 25% of those receiving placebo (7 of 28) reported improved energy levels (P < 0.1).
Among the 26 patients with an Axis 1 depressive disorder at baseline, 58% of the testosterone-treated patients reported improved mood in comparison with 14% of placebo-treated patients (Fisher's exact test = 0.08).
Following testosterone treatment, the average increase in muscle mass over 12 weeks was 1.6 kg for the whole group, and 2.2 kg for the 14 men with wasting at baseline.
Improvement in all parameters assessed was maintained during subsequent open-label treatment for up to 18 weeks.
Rabkin et al.115 concluded that testosterone is well tolerated and effective in the short-term treatment of clinical hypogonadism in men with symptomatic HIV infections, restoring libido and energy, alleviating depressed mood and increasing muscle mass.
Rietschel et al.116 discussed the findings of previous studies which have indicated a significant prevalence (50%) of hypogonadism among men with AIDS-associated wasting. For these patients, testosterone administration has been shown to increase lean body mass and improve quality of life. However, the prevalence of hypogonadism had not previously been investigated among men with weight loss related to HIV infection who had been receiving HAART. From 1997 to 1999, Rietschel et al.116 studied total and free testosterone levels in 90 men who were < 90% of ideal body weight or had weight loss of > 10% from their pre-illness weight. Seventy-one per cent of these patients were receiving HAART. Rietschel et al.115 found that 21% of the patients who were receiving HAART had low FT levels. They did not find any correlation between low FT levels and weight, CD4 cell count, medication status and other clinical factors. They concluded that these data would suggest that hypogonadism remains relatively common in men with AIDS wasting, despite treatment with HAART, and that HIV-infected men with wasting syndrome should be screened for hypogonadism and should receive physiological androgen replacement therapy if they are hypogonadal.
In 2003, Dobs117 stated that low testosterone levels are common in both men and women with HIV infection, and this may contribute to the loss of lean body mass and AIDS wasting. Dobs also commented that the causes of low testosterone levels are complex and may include chronic illness, HIV infection and its complications, medications used to treat HIV and opportunistic diseases, and normal ageing-related declines.117 In addition, Dobs reported that (1) in the majority of studies that addressed the use of testosterone treatment in HIV-infected patients, testosterone had been found to help prevent loss of body and muscle mass; (2) whether the combination of exercise and testosterone is more effective in preventing loss of lean body mass than either therapy alone is not yet clear and warrants further study; and (3) in addition to its effects on body composition, testosterone treatment results in improved mood and libido in HIV-infected women and increased BMD in HIV-infected men.117 Dobs also suggested that testosterone may make a valuable contribution to the treatment of HIV-infected individuals.117
Collazos118 searched MEDLINE for articles dealing with any manifestations of sexual dysfunction in the HAART era. A review of selected articles indicated that sexual dysfunction seems to be a very common event after the introduction of HAART. Average prevalences among the different studies were 51% for sexual dysfunction, 46% for erectile dysfunction, 44% for decreased libido, 39% for ejaculatory disturbances and 27% for orgasmic disorders. Collazos also stated that these disturbances seemed to be more common in patients treated with protease inhibitors.118
Le Tortorec and Dejucq-Rainsford119 pointed out that several receptors on spermatozoa could allow HIV-specific binding during their progression through the male genital tract. Hence, they argued, it is likely that spermatozoa can act as a carrier for viral particles encountered within, for example, the testis or epididymis, in the absence of seminal plasma, which acts as an inhibitor for some of the HIV receptors present on spermatozoa. The authors commented that it has been established that spermatozoa do not produce HIV particles, adding that whether they can support the early steps of HIV replication (for example, up to viral DNA synthesis), as proposed by some authors, remains speculative. This is because the vast majority of studies have not shown evidence of any HIV genetic material and spermatozoa are considered to be metabolically inert cells. Nevertheless, they posit that non-specific mechanisms such as foreign RNA uptake could be at play and may explain the detection of HIV DNA in a subset of abnormal spermatozoa. The authors conclude that the exact nature of the interactions between HIV and spermatozoa, and their impact on morphology, are far from fully understood and require further studies.
Le Tortorec and Dejucq-Rainsford119 also indicated that, according to recent data, the testis is infected early during the course of HIV infection and this infection is not associated with any apparent change in testicular morphology or inflammation of the organ. They observed that testicular leucocytes represent the main target cells for the virus, but that testicular germ cells also occasionally associate with HIV. This is important to bear in mind for the purposes of intracytoplasmic sperm injection using testicular germ cells from HIV-infected individuals.119 The authors noted that the presence of HIV receptors on human testicular germ cells, and the molecular interactions between these cells and HIV, is currently being investigated. Whether or not the testis constitutes a viral sanctuary despite antiretroviral therapy is also under study.119
A number of studies120–122 have shown evidence of HIV in immune cells infiltrating the epididymis, prostate and seminal vesicles of men at the AIDS stage. The same has been observed in macaques.123 However, what happens during the early and asymptomatic stages of the disease has not been studied.119
Le Tortorec et al.124 confirmed that the human prostate is susceptible to HIV-1 infection ex vivo. The prostate was found to be preferentially infected by HIV-1 R5 strains (the sexually transmitted strains) in comparison with X4 strains, which are not sexually transmitted and appear during the later stages of the disease.
Le Tortorec and Dejucq-Rainsford119 stipulated that, as HIV may persist and be shed intermittently in semen from men who are being effectively treated with HAART and are free of other sexually transmitted infections,125,126 there is a need to test not only the blood viraemia but also the seminal viral load – in several measurements, some time apart – in order to assess the risk of sexual transmission from each individual receiving HAART. This also stresses the importance of determining the nature of the reservoirs responsible for HIV shedding in semen, in order to design more effective therapeutic strategies that can eradicate the virus from semen.
Wyatt et al.127 stated that renal disease is a fairly common complication in patients with HIV infection. HIVN may ensue from direct kidney infection with HIV or from the adverse effects of antiretroviral drugs.128 Treatment with cotrimoxazole (Bactrim®, Roche) may result in hyperkalaemia, hyponatraemia and acute renal failure. Patients receiving amphotericin may suffer hypokalaemia, hypernatraemia, hypocalcaemia, hypomagnesaemia and acute renal failure. For those on pentamidine, effects may include hyperkalaemia, hypocalcaemia, hypomagnesaemia and acute renal failure. Treatment with itraconazole may lead to hyponatraemia and hyperkalaemia. Foscarnet may cause hypernatraemia, hyperkalaemia, hypomagnesaemia, hypo- or hypercalcaemia, low or high phosphate levels and acute renal failure.129 Atta et al.130 also discussed the role of antiretroviral drugs in patients with HIVN.
In addition, pursuant to nausea, vomiting, poor nutrition and salt wasting, patients with HIV infection may be at risk of developing renal failure due to volume depletion. HIV nephropathy, previously referred to as AIDS-associated nephropathy, is characterized by the following observations:
nephrotic range proteinuria
observation of normal to large kidneys on ultrasound scan images
normal blood pressure
evidence of focal segmental glomerulosclerosis (FSGS) in renal biopsy specimens.129
In addition to FSGS, which is the predominant glomerular lesion in HIVN, other reported lesions in patients with HIV infection include IgA nephropathy, cryoglobulinaemia, amyloidosis and lupus-like immune complex glomerulopathy.129
Phar and Patella131 stated that, prior to the introduction of antiretroviral therapy, HIVN was characterized by rapid progression to renal failure and ESRD necessitating dialysis. However, with the advent of HAART this is no longer the case, highlighting the importance of prompt diagnosis and proper care of the patient. To this end, Phar and Patella131 recommended that baseline eGFR of patients with HIV infection should be obtained and renal function monitored during HAART, and that physicians must consider HIVN in patients who develop proteinuria.
Larsen et al.133 stated that subclinical persistent fungal prostatitis caused by Cryptococcus neoformans occurs in up to 29% of patients after successful treatment. Mitchell and Perfect133 noted that this is an important reservoir for subsequent relapse of cryptococcal meningitis. These patients are given long-term antifungal prophylaxis.133
Documented problems associated with HIV infection and AIDS include opportunistic infections of genitourinary tract organs; functional and structural renal problems; tumours of the penis, bladder and other organs of the genitourinary tract; voiding problems including urinary retention; ureteric obstruction; impotence; and malignancies including Kaposi's sarcoma, non-Hodgkin's lymphoma, germ cell tumours of the testis and other malignancies.