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Special considerations in the management of erectile dysfunction in the HIV-positive patient
Abstract
Restoration of sexual function to HIV-positive men with erectile dysfunction (ED) is a challenging problem with many faces.
Interactions between the novel phosphodiesterase inhibitors for treatment of ED and the highly active antiretroviral therapy
(HAART) that currently forms the foundation of medical therapy for HIV infection require appropriate dose adjustment and familiarity
with common medical conditions affecting the HIV-positive man. Urologists and general practitioners caring for this group
of patients will also have to consider legal precedents governing delivery of care to HIV-positive patients in a new scenario
in which the traditional physicianpatient encounter is affected by a third party—the patient’s current and future partner(s)
and his or her respective rights.
... The physician managing the patient with HIV should also have some expertise in sexual medicine and not be reluctant or embarrassed when interviewing the patient about his sexuality. 76,77,88 Sexual dysfunction should, therefore, be approached in the same way as other HIV-related comorbidities (such as cardiovascular or metabolic disorders) and a special ist in sexual medicine should be part of the multi disciplinary management. The physician should provide efforts to ensure a satisfactory sex life, which is a basic human right. ...
... 89 Usually, men with HIV receive information on safer sex at the time of diagnosis and all such information should be reoffered when starting a treatment for ED. Several authors have warned about the prescription of drugs enhancing erectile function to men with HIV; 71,74,77,78,88 however, a better erection avoids risky sexual behaviour such as condom slippage or voluntary removal during sex. 63 ...
Sexual dysfunction in men with HIV is often overlooked by clinicians owing to many factors, including the taboo of sexuality. The improved life expectancy of patients with HIV requires physicians to consider their general wellbeing and sexual health with a renewed interest. However, data on sexual dysfunction in those with HIV are scarce. Erectile dysfunction (ED) is the most common sexual dysfunction in men, with a prevalence of ∼30-50% and is frequent even in men <40 years of age. HIV infection itself is the strongest predictor of ED, and many factors related to the infection-fear of virus transmission, changes in body image, HIV-related comorbidities, infection stigma, obligatory condom use-all impair erectile function. The diagnosis and treatment of sexual dysfunction is based on a multidisciplinary approach, which involves specialists in both infectious diseases and sexual medicine. Particular attention should be paid to the promotion of safer sex in these patients. This Review, describes the issues surrounding sexual dysfunction in men with HIV and aims to provide clinical advice for the physician treating these patients.
Context While recent pharmacological advances have generated increased public interest and demand for clinical services regarding erectile dysfunction, epidemiologic data on sexual dysfunction are relatively scant for both women and men. Objective To assess the prevalence and risk of experiencing sexual dysfunction across various social groups and examine the determinants and health consequences of these disorders. Design Analysis of data from the National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative, 1992 cohort of US adults. Participants A national probability sample of 1749 women and 1410 men aged 18 to 59 years at the time of the survey. Main Outcome Measures Risk of experiencing sexual dysfunction as well as negative concomitant outcomes. Results Sexual dysfunction is more prevalent for women (43%) than men (31%) and is associated with various demographic characteristics, including age and educational attainment. Women of different racial groups demonstrate different patterns of sexual dysfunction. Differences among men are not as marked but generally consistent with women. Experience of sexual dysfunction is more likely among women and men with poor physical and emotional health. Moreover, sexual dysfunction is highly associated with negative experiences in sexual relationships and overall wellbeing. Conclusions The results indicate that sexual dysfunction is an important public health concern, and emotional problems likely contribute to the experience of these problems.
Aims To investigate the effect of the antiretroviral protease inhibitors saquinavir (soft gelatin capsule) and ritonavir on the pharmacokinetic properties and tolerability of sildenafil and to investigate the effect of sildenafil on the steady-state pharmacokinetics of saquinavir and ritonavir.
Methods Two independent, 8 day, open, randomized, placebo-controlled, parallel-group studies (containing a double-blind crossover phase) were conducted at Pfizer Clinical research units (Canterbury, UK. and Brussels, Belgium). Twenty-eight healthy male volunteers entered each study. In each study, volunteers were randomized (n = 14 per group) to receive sildenafil on day 1 followed by a 7-day treatment period (days 2–8) with saquinavir or placebo (Study I) or ritonavir or placebo (Study II). Sildenafil or placebo (Study I and Study II) was administered alternately on day 7 or day 8, depending on initial randomization. The effect of saquinavir and ritonavir on the pharmacokinetics of sildenafil and its primary circulating metabolite (UK-103, 320) and the effect of single-dose sildenafil on the steady-state pharmacokinetics of saquinavir (1200 mg three times daily) and ritonavir (500 mg twice daily) were determined. The safety and tolerability of sildenafil coadministered with saquinavir or ritonavir were also assessed.
Results Both protease inhibitors significantly increased Cmax, AUC, tmax and t½ values for both sildenafil and UK-103, 320. Ritonavir showed a significantly greater effect than saquinavir with increases in sildenafil AUC and Cmax of 11-fold (95% CI: 9.0, 12.0) and 3.9-fold (95% CI: 3.2, 4.9), respectively. This compared with increases of 3.1-fold (95% CI: 2.5, 4.0) and 2.4-fold (95% CI: 1.8, 3.3) for coadministration with saquinavir. In contrast, the steady-state pharmacokinetics of saquinavir and ritonavir were unaffected by sildenafil. The increases in systemic exposure to sildenafil and UK-103, 320 were not associated with an increased incidence of adverse events or clinically significant changes in blood pressure, heart rate or ECG parameters.
Conclusions These results indicate that both saquinavir and ritonavir modify the pharmacokinetics of sildenafil presumably through inhibition of CYP3A4. The more pronounced effect of ritonavir may be attributed to its additional potent inhibition of CYP2C9. No change in safety or tolerability was observed when sildenafil was coadministered with either protease inhibitor. However, given the extent of the interactions, a lower sildenafil starting dose (25 mg) should be considered for patients receiving saquinavir and it is recommended not to exceed a maximum single dose of 25 mg in a 48 h period for patients receiving ritonavir.
Condoms were tested in an in vitro system simulating key physical conditions that can influence viral particle leakage through condoms during actual coitus. The system quantitatively addresses pressure, pH, temperature, surfactant properties, and anatomical geometry. A suspension of fluorescence-labeled, 110-nm polystyrene microspheres models free human immunodeficiency virus (HIV) in semen, and condom leakage is detected spectrofluorometrically. Leakage of HIV-sized particles through latex condoms was detectable (P less than 0.03) for as many as 29 of the 89 condoms tested. Worst-case condom barrier effectiveness (fluid transfer prevention), however, is shown to be at least 10(4) times better than not using a condom at all, suggesting that condom use substantially reduces but does not eliminate the risk of HIV transmission.
While recent pharmacological advances have generated increased public interest and demand for clinical services regarding erectile dysfunction, epidemiologic data on sexual dysfunction are relatively scant for both women and men.
To assess the prevalence and risk of experiencing sexual dysfunction across various social groups and examine the determinants and health consequences of these disorders.
Analysis of data from the National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative, 1992 cohort of US adults.
A national probability sample of 1749 women and 1410 men aged 18 to 59 years at the time of the survey.
Risk of experiencing sexual dysfunction as well as negative concomitant outcomes.
Sexual dysfunction is more prevalent for women (43%) than men (31%) and is associated with various demographic characteristics, including age and educational attainment. Women of different racial groups demonstrate different patterns of sexual dysfunction. Differences among men are not as marked but generally consistent with women. Experience of sexual dysfunction is more likely among women and men with poor physical and emotional health. Moreover, sexual dysfunction is highly associated with negative experiences in sexual relationships and overall well-being.
The results indicate that sexual dysfunction is an important public health concern, and emotional problems likely contribute to the experience of these problems.
Urologists and health care professionals treating erectile dysfunction face a significant challenge in caring for the HIV-positive patient who seeks restoration of normal sexual function. The encounter between the health care provider and the patient in this setting requires knowledge of HIV disease and potential drug interactions specific to this population, as well as thorough counseling on strategies aimed at reducing the infectiousness of HIV-1. The interaction extends beyond the immediate boundaries of the doctor-patient relationship and their respective rights, to include careful consideration of the rights of the partner/s and the society as a whole. This paper is a summary and analysis of presentations and discussions by medical, legal, nursing and bioethics specialists in an interactive seminar on this topic.
A high proportion of individuals receiving highly active antiretroviral treatment (HAART) complain of sexual dysfunction (SD), encompassing a lack of desire or erectile dysfunction.
To determine whether SD was associated with particular components of the HAART regimens and to identify risk factors for the development of SD in patients on HAART.
A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. A total of 904 individuals currently receiving antiretroviral agents were included in the analyses.
A decrease in sexual interest was significantly more frequently reported by subjects (men and women) using HAART containing protease inhibitors (PI) (308/766, 40%), compared with PI-naive patients (22/138, 16%; OR 3.55; 95% CI 2.15--5.89). In addition, a significantly larger number of PI-experienced men reported a decrease in sexual potency (216/628, 34%) compared with PI-naive men (12/99, 12%; OR 2.56; 95% CI 1.33--5.03). In multivariate analyses the following factors were associated with a decrease in sexual interest: a current PI-containing regimen, a history of a PI regimen, symptomatic HIV infection, age and homosexual contact as HIV transmission mode. Factors associated with a decrease in sexual potency were: current use of a PI-containing regimen, symptomatic HIV disease, age and the use of tranquillisers.
SD appears to be a common side-effect of HAART regimens containing a PI. The potential association between SD and other side-effects of HAART, such as lipodystrophy syndrome and neuropathy, should be investigated further.
Background/objective: There is concern that use of highly active antiretroviral therapy (HAART) may be linked to increased sexual risk behaviour among homosexual men. We investigated sexual risk behaviour in HIV positive homosexual men and the relation between use of HAART and risk of HIV transmission.
A cross sectional study of 420 HIV positive homosexual men attending a London outpatient clinic. Individual data were collected from computer assisted self interview, STI screening, and clinical and laboratory databases.
Among all men, sexual behaviour associated with a high risk of HIV transmission was commonly reported. The most frequently reported type of partnership was casual partners only, and 22% reported unprotected anal intercourse with one or more new partners in the past month. Analysis of crude data showed that men on HAART had fewer sexual partners (median 9 versus 20, p=0.28), less unprotected anal intercourse (for example, 36% versus 27% had insertive unprotected anal intercourse with a new partner in the past year, p=0.03) and fewer acute sexually transmitted infections (33% versus 19%, p=0.004 in the past 12 months) than men not on HAART. Self assessed health status was similar between the two groups: 72% on HAART and 75% not on HAART rated their health as very or fairly good, (p=0.55). In multivariate analysis, differences in sexual risk behaviour between men on HAART and men not on HAART were attenuated by adjustment for age, time since HIV infection. CD4 count and self assessed health status.
HIV positive homosexual men attending a London outpatient clinic commonly reported sexual behaviour with a high risk of HIV transmission. However, behavioural and clinical risk factors for HIV transmission were consistently lower in men on HAART than men not on HAART. Although use of HAART by homosexual men with generally good health is not associated with higher risk behaviours, effective risk reduction interventions targeting known HIV positive homosexual men are still urgently needed.
objective: There is concern that use of highly active antiretroviral therapy (HAART) may be linked to increased sexual risk behaviour among homosexual men. We investigated sexual risk behaviour in HIV positive homosexual men and the relation between use of HAART and risk of HIV transmission.Methods: A cross sectional study of 420 HIV positive homosexual men attending a London outpatient clinic. Individual data were collected from computer assisted self interview, STI screening, and clinical and laboratory databases. Results: Among all men, sexual behaviour associated with a high risk of HIV transmission was commonly reported. The most frequently reported type of partnership was casual partners only, and 22% reported unprotected anal intercourse with one or more new partners in the past month. Analysis of crude data showed that men on HAART had fewer sexual partners (median 9 versus 20, p=0.28), less unprotected anal intercourse (for example, 36% versus 27% had insertive unprotected anal intercourse with a new partner in the past year, p=0.03) and fewer acute sexually transmitted infections (33% versus 19%, p=0.004 in the past 12 months) than men not on HAART. Self assessed health status was similar between the two groups: 72% on HAART and 75% not on HAART rated their health as very or fairly good, (p=0.55). In multivariate analysis, differences in sexual risk behaviour between men on HAART and men not on HAART were attenuated by adjustment for age, time since HIV infection. CD4 count and self assessed health status.Conclusion: HIV Positive homosexual men attending a London outpatient clinic commonly reported sexual behaviour with a high risk of HIV transmission. However, behavioural and clinical risk factors for HIV transmission were consistently lower in men on HAART than men not on HAART. Although use of HAART by homosexual men with generally good health is not associated with higher risk behaviours, effective risk reduction interventions targeting known HIV positive homosexual men are still urgently needed.
Increasing numbers of HIV-positive men receiving protease inhibitors (PI) complain of erectile dysfunction (ED). Through the analysis of 334 HIV-1-infected male outpatients, this study shows homosexuality, CD4 cell count, viral load, and indinavir treatment to be independent variables predictive of ED. Furthermore, a neuropathy of the sacral region was detected in 12 patients with ED who underwent diagnostic investigations. For the first time, a PI-containing regimen has been associated with peripheral neuropathy causing ED.
Objectives: The prevalence of erectile dysfunction in HIV-infected men is estimated to be 33%. Sildenafil citrate (Viagra; Pfizer Ltd, Sandwich, Kent, UK) is the first oral drug for this condition. Since sildenafil and the protease inhibitors are both metabolized by, and act as inhibitors of cytochrome P450 3A4, we evaluated the pharmacokinetics of the combination sildenafil plus indinavir in HIV-infected patients.
Design and methods: Six patients at steady state in treatment with indinavir participated in the study. On the first day blood samples for indinavir assay were drawn at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. On the second study day patients received a single dose of 25 mg of sildenafil in addition to their routine morning medication. Blood samples were taken as described. Separated plasma was stored at -80°C until analysis by high performance liquid chromatography. In a parallel study, the effect of indinavir, ritonavir, saquinavir and nelfinavir on the in vitro hepatic metabolism of sildenafil was assessed.
Results: The geometric mean area under the concentration curve for 0-8h (AUC0-8h) and maximum plasma concentration (Cmax) for indinavir were 19.69μg/mlh (range, 9.19-31.99μg/mlh) and 7.02μg/ml (range, 2.33-16.17μg/ml), respectively, on the first study day. In the presence of sildenafil, the mean AUC0-8h and Cmax of indinavir were 22.37μg/mlh [range, 10.08-37.25μg/mlh; 95% confidence interval (CI) for difference between means, -15 to 13.25) and 9.11μg/ml (range, 3.41-22.78μg/ml; 95% CI, -13 to 6.37), respectively.
The geometric mean AUC0-8h and Cmax for sildenafil were 1631 ng/mlh (range, 643-2970 ng/mlh) and 384 ng/ml (range, 209-766 ng/ml) respectively. The AUC for sildenafil was 4.4 times higher than data from historical controls given either 50mg or 100 mg of sildenafil and dose normalized to 25 mg. Indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro [concentration producing 50% inhibition of control enzyme activity (IC50) = 0.39 ± 0.17 μM, mean ± SD].
Conclusions: Co-administration of sildenafil 25 mg did not significantly alter the plasma indinavir levels. However, plasma sildenafil AUC was markedly increased in the presence of indinavir compared with historical controls. From the in vitro data, the mechanism of increase is indinavir inhibition of the hepatic metabolism of sildenafil. The magnitude of this interaction suggests a lower starting dose of sildenafil may be more appropriate in this clinical setting.
HIV infection can be associated with major psychological and social disturbance. Psychosexual problems would be expected to arise in the context of the infection, in view of the contribution that sexual behaviour can make to the acquisition and spread of HIV infection. Here the results of a study of the psychosexual consequences of HIV infection in gay men and men with haemophilia are presented, with the inclusion of data from control groups. Sixteen HIV-positive and 23 HIV-negative gay men, and 20 HIV-positive and 24 HIV-negative men with haemophilia with sexual partners were studied. HIV infection was found to be associated with the greater risk of development of sexual dysfunction in seropositives, in particular in relation to ejaculatory difficulties, both delayed ejaculation in the case of gay men and men with haemophilia, and premature ejaculation in the case of men with haemophilia. Possible aetiological mechanisms are considered, including the possibility of organic disease. The findings are of relevance to those involved in the care of people with HIV infection.
Value of the bulbocavernosus reflex latency versus nerve conduction velocity of the dorsal nerve of penis and penile brachial index was evaluated in HIV-1 infected asymptomatic and symptomatic men with and without an objective evidence of neuropathy. These studies revealed striking results in neuropathic group. Both asymptomatic and symptomatic patients with neuropathy exhibited a significant decrease (P < 0.0005) in the values of the nerve conduction velocity of the dorsal nerve of penis as well as penile brachial index in comparison with the controls of the same age group. However both types of non neuropathic patients showed a non significant difference in the above mentioned parameters with their respective controls. The latency of bulbocavernosus reflex showed no significant difference between the groups and was within the normal limits. A non significant association in the values of the study parameters among asymptomatic and symptomatic patients with and without neuropathy was also observed. These findings suggest an exclusively apparent sexual pathway for the penile dorsal nerve conduction and penile brachial index in both HIV-1 infected asymptomatic and AIDS positive men affected by neuropathic conditions, irrespective of their disease state. We thus conclude that a primary defective neuropathic mechanism may play an etiological role in the pathogenesis of erectile impotence in these patients.
Although there is an emerging body of literature on quality of life in persons with human immunodeficiency virus (HIV) disease (Barker et al., 1990; Wu et al., 1990; Wachtel et al., 1992), there is a paucity of published data on the prevalence of sexual dysfunction in HIV-infected persons or on the impact of such dysfunction on quality of life. One previous study has reported that 67% of homosexual men with acquired immunodeficiency syndrome (AIDS) reported a decreased libido and 33% reported impotency (Dobbs et al., 1993). We here describe the findings from an investigation of sexual dysfunction in a large group of homosexual men with severe HIV disease.
We provide current, normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a community based, random sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston, Massachusetts. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. We conclude that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena.
Older Americans, 50 years of age and older, account for 10% of the 400,000 reported cases of AIDS nationwide (Centers for Disease Control and Prevention, 1994). the integrated literature review format in this article examines the published literature on HIV/AIDS in older adults. Most articles are case studies and reports, with only 17% having a research basis. The information reviewed indicates that older adults have different risk factors than younger populations for contracting HIV disease and a different pattern of disease progression. These differences create a need for knowledge of HIV infection and AIDS and its parameters in aging populations so nurses may provide both timely and appropriate care.
The use of highly active antiretroviral therapy to control infection with human immunodeficiency virus type 1 (HIV-1) is in many ways a success story. Under optimal circumstances, combinations of drugs that inhibit the viral protease and reverse transcriptase suppress replication to below the limits of detection in the circulation. The production of the virus is stifled at its source in lymphatic tissues, and the large pools of virus stored in that reservoir are reduced to undetectable levels.1,2 The control of viral replication benefits the ravaged immune system, even in the late stages of infection. The numbers of CD4+ T . . .
Sexual functioning is often neglected in the care of HIV-infected patients. Little information exists about the relationship between hormonal factors, psychological factors, medication, HIV disease stage and sexual functioning among persons with HIV disease. In this study, 50 HIV+ men completed the Derogatis Sexual Functioning Inventory (DSFI), and had serum hormonal assays drawn (testosterone, thyroid function test, leuteinizing hormone, prolactin and oestradiol). Although all the subjects reported some degree of sexual dysfunction, persons with symptomatic HIV/AIDS reported more negative mood, lower sexual satisfaction scores and worse body image than persons with asymptomatic HIV. Persons with asymptomatic HIV also tended to have normal testosterone levels compared with persons with symptomatic HIV/AIDS. No relationship was found between medications and low testosterone, although numbers were small. These results suggest that sexual dysfunction is prevalent among persons with HIV disease, is more common as patients become symptomatic and progress to AIDS and that both physiological (low testosterone) and psychological issues play a role.
The Americans With Disabilities Act (ADA) was widely hailed at the time of its enactment in 1990 as providing broad protection against disability discrimination, including discrimination against individuals infected with the human immunodeficiency virus (HIV). In the years since its enactment, however, courts frequently interpreted the ADA as providing far less protection than was initially anticipated. The Supreme Court's first case involving HIV and the acquired immunodeficiency syndrome, Bragdon v Abbott, addressed this trend by ruling that a woman with asymptomatic HIV infection is protected from discrimination in accessing dental services. In doing so, the Court endorsed an interpretation of the ADA that is broadly protective for individuals with disabilities. The Court also ruled that health care professionals may legally refuse to treat a patient because of concern that the patient poses a direct threat to safety only if there is an objective, scientific basis for concluding that the threat to safety is significant. In addition to the ADA, state laws frequently prohibit disability discrimination and apply to some employers and others not regulated by federal law. A state-by-state survey of those laws demonstrates that, consistent with Bragdon v Abbott, individuals with asymptomatic HIV have widespread protection on the state level.
Sexual dysfunction problems are common in people with HIV infection, but their relevance has been recently highlighted in response to the increased survival shown by many individuals with HIV, and the publicity surrounding the development of new treatments for male sexual dysfunction. Thirty-four gay/bisexual men with HIV infection presenting with sexual dysfunction were assessed. Antiretroviral combination therapy including protease inhibitors was taken by 44%, other combinations not including protease inhibitors by 24%, while 32% were not taking any antiretrovirals. Primarily psychogenic sexual dysfunction was thought to be present in 44%, primarily organic dysfunction in 22% and a mixed aetiology in 34%. Treatments offered included psychological interventions and physical methods of treatment, alone or in combination. Treatment was effective, with 76% reporting resolution of the problems, 14% reporting improvement and only 10% reporting no change. Practical and ethical issues raised by the findings are discussed.
The objective of the study was to determine whether treatment with protease inhibitors is associated with unprotected sexual behavior.
A total of 592 HIV-infected persons recruited from statewide public clinics in nonurban Alabama communities completed an assessment that, among other variables, elicited information on demographics, current sexual practices, health status, and medication use. Associations of treatment with protease inhibitors and high-risk sexual behavior were estimated, adjusting for potential confounders.
Treatment with protease inhibitors was not associated with whether a person was sexually active or with high-risk practices among sexually active heterosexual men and women. Among men who had sex with men, however, treatment with protease inhibitors was associated with never using condoms and with inconsistent use of condoms.
Clinicians treating patients with protease inhibitors should consider providing risk-reduction counseling.
We conducted a cross-sectional study of 156 ambulatory HIV-infected homosexual or bisexual men to assess and compare the prevalence and characteristics of sexual dysfunction according to treatment combinations (group A, protease inhibitor [PI] treatment; group B, no PI treatment; and C, PI treatment interrupted >1 month previously). The study was based on a self-administered 163-item questionnaire that included a French translation of the International Index of Erectile Function, five sections of the Derogatis Sexual Functioning Inventory, and open questions. Data analysis was performed using Mann-Whitney and Kruskal-Wallis H nonparametric tests (quantitative values) and chi2 tests (qualitative values) using SPSS software (SPSS, Chicago, IL, U.S.A.). One hundred fifty-six patients completed the study. The median age +/- SD of the patients was 40.5 +/- 7.7 years, and the median CD4+ cell count +/- SD was 415 +/- 236/mm3. One hundred eleven (71%) of 156 patients reported some degree of sexual dysfunction since the beginning of their treatment (65 [71%] of 91 group A patients; 15 [65%] of 23 group B patients; and 31 [74%] of 42 group C patients), with no significant difference among the groups. Of the 111 patients, 99 (89%) reported decrease or loss of libido, 76 (68%) reported orgasmic perturbation, 96 (86%) reported erectile dysfunction, and 65 (59%) reported ejaculation perturbation, with no significant difference among the three groups. There were no significant differences among the three groups regarding the International Index of Erectile Function and Derogatis Sexual Functioning Inventory scores. These data suggest that PI-based therapy does not seem to increase sexual dysfunction in this patient population.
Sexual disturbances have been related to protease inhibitor therapy, but the effect of specific protease or non-nucleoside reverse transcriptase inhibitors is largely unknown. We analysed the rate of sexual dysfunction and the sexual hormonal profile in patients undergoing antiretroviral therapy. All antiretroviral drugs were associated with different degrees of sexual dysfunction; the highest rates with indinavir and the lowest with nevirapine. Although these drugs were associated with increases in testosterone and 17 beta-oestradiol, sexual disturbances were not related to alterations in the sexual hormonal pattern.
To determine whether treatment with protease inhibitors (PIs) is associated with male sexual dysfunction, we conducted a retrospective, cohort study of 254 adult male PI recipients who received care from the staff-model division of a large managed care organization in New England between 1993 and 1998. After a median of 5.0 years of observation, 80 incident cases of sexual dysfunction were observed. Relative to unexposed individuals, the rate of sexual dysfunction adjusted for confounding was most elevated with use of ritonavir (hazard ratio [HR], 2.83; 95% confidence interval [CI], 1.34-5.97; p =.006) followed by indinavir (HR, 1.69; 95% CI, 0.84-3.37; p =.14), nelfinavir (HR, 1.53; 95% CI, 0.66-3.54; p =.32) and saquinavir (HR, 1.25; 95% CI, 0.53-2.96; p =.60). We conclude that PIs, especially ritonavir, appear to increase the risk of sexual dysfunction.
Sexual dysfunction and depression are very common conditions that are age-related and chronic. In men, epidemiologic studies have confirmed a strong correlation between erectile dysfunction and symptoms of depression. Both conditions have a significant negative impact on the quality of life of patients and their partners. Several studies showed that restoration of normal sexual function improves the quality of life of patients and their partners, regardless of treatment method. The literature review and recent observations emphasize the multifactorial nature of sexual dysfunction and, more specifically, erectile dysfunction and underline the importance of the comorbidity and bidirectional relationship between erectile dysfunction and depression. Research is progressing on the possible link between andropause, sexual dysfunction, and depression, thus opening potential new opportunities to address issues of aging-related morbidities.
Sexual disturbances develop in some patients treated with highly active antiretroviral therapy (HAART). To evaluate sexual dysfunction and the influence that different antiretrovirals could have on those parameters, we conducted a prospective study in patients with stable clinical condition attending an HIV outpatient clinic. A total of 351 evaluations were performed in 189 HIV-infected men, who were interviewed about symptoms of sexual dysfunction. Sexual hormones as well as other clinical and laboratory parameters were also measured at the time of each evaluation. The mean CD4 count was 451.1 x 10(6) cells/L, and viral load was undetectable in two thirds of the determinations. The prevalence of sexual dysfunction was 19.5% overall, but it was influenced by treatment, particularly (although not exclusively) by protease inhibitors (PIs) (27.1% vs. 3.8% for untreated patients). Sexual dysfunction was not related to hypophyseal or gonadal hormonal values. Although several parameters were associated with sexual dysfunction in the univariate analysis, only antiretroviral treatment was significantly predictive of this disorder in a logistic regression analysis. Sexual dysfunction is common in HIV-infected patients in stable clinical condition receiving HAART, and all antiretroviral drugs, particularly PIs, seem to be related to it. Sexual dysfunction in these patients is not related to hormonal causes.
We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health-related quality of life (HRQL).
Medical data for patients in the French APROCO cohort were collected at enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey) and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a "normal HRQL." RESULTS. Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm, time since HIV diagnosis <8 years, undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12.
An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long-term strategies properly and to optimize the durability of response to antiretroviral therapy.
The management of HIV infection has dramatically altered the natural history of the disease. Prevention of opportunistic infections and the development of HAART regimens altered the manifestations and conditions that urologists are being asked to evaluate and manage in this patient population.
The objective of this study was to investigate if sildenafil influences the pharmacokinetics of nelfinavir. Five HIV-infected patients on steady-state nelfinavir-containing therapy were subject to pharmacokinetic sampling for nelfinavir concentration twice: without sildenafil and with sildenafil 25 mg as a single dose. There were no differences in the AUC, T(max), or C(max) of nelfinavir. In a similar design, two patients on indinavir and two patients on ritonavir combined with saquinavir were studied. In accordance with the literature, neither of these two treatments was affected. It is concluded that nelfinavir pharmacokinetics were unaffected by concomitant intake of a single dose of sildenafil.
Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease.
We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist.
The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED.
ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.
This article examines the relationships among depression, ischemic heart disease, and erectile dysfunction. Depression is an independent risk factor for the development of ischemic heart disease, and depression in the post-myocardial infarction patient is associated with increased morbidity and mortality. Ischemic heart disease and erectile dysfunction are also frequently comorbid and share many common risk factors including age, hypertension, diabetes, dyslipidemia, obesity, sedentary lifestyle, and smoking. Depression and erectile dysfunction often occur together; however, the causal relation may be difficult to determine because erectile dysfunction may be a symptom of depression, social distress accompanying erectile dysfunction may precipitate depressive symptoms, or both conditions may result from a common factor such as vascular disease.
The association between different antihypertensive drugs and erectile dysfunction (ED) was examined in a cohort of type II diabetes patients identified in the UK General Practice Research Database (GPRD). The GPRD contains details of diagnoses, prescribing, investigations, risk factors, outcomes, and hospital referrals, together with basic demographic information for approximately six million patients from more than 450 representative general practices throughout the UK. A total of 634 cases and 2526 controls were included for analysis. Unconditional logistic regression analysis was performed to assess the risk of ED after adjusting for age at diabetes diagnosis date, cigarette smoking, depression, glycemic control, use of HMG-CoA reductase inhibitors, use of histamine receptor antagonists, use of digitalis medicines, and use of nitrates. Increased risk of ED was observed among patients taking the following antihypertensives: ACE inhibitors (OR=1.47, 95% CI=1.21, 1.80) and alpha blockers (OR=1.54, 95% CI=1.11, 2.12). However, we identified a nearly 30% reduction in risk among patients on diuretics (OR=0.73, 95% CI=0.54, 0.99). No statistically significant increase in risk was observed among users of beta blockers and calcium channel blockers (OR=1.05, 95% CI=0.85, 1.31) and (OR=1.14, 95% CI=0.91, 1.43), respectively. The results of this study confirm the strong and recognized effect of comorbidities in a diabetic population, but also require additional experimental and observational studies to further understand the potential benefit of diuretics and other ED treatments such as PDE5 inhibitors.
AIDS and the urologist An excellent review of common problems facing urologists in the HIV/AIDS era
- G Hyun
- Lowe
Interaction of sildenafil and indinavir when co-administered to HIV-positive patients This is one of the few in-depth publications on the topic of PDE5-protease inhibitor interaction
- Barry C Merry
- Mg
- M Ryan
- Jf Tjia
- M Hennessy
- Eagling
- Va
Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir This is one of the few in-depth publications on the topic of PDE5-protease inhibitor interaction
- Gj Muirhead
- Mb Wulff
- A Fielding
Disability discrimination in America: HIV/AIDS and other health conditions One of the most important reviews of the legal issues in physician interactions with HIV-positive patients
- Lo Gostin
- C Feldblum
- Webber
AE: The Changing Face of AIDS
- Oliva Dag
- DaG Oliva
Ct ed; 1998:2207. The landmark US Supreme Court case categorizing asymptomatic HIV-positive status as a disability worthy of inclusion in the Americans with Disabilities Act
- Bragdon V Abbott
The landmark US Supreme Court case categorizing asymptomatic HIV-positive status as a disability worthy of inclusion in the Americans with Disabilities Act
- Abbott Bragdon V
Protease inhibitor combination therapy and decreased condom use among gay men
- R J Diclemente
- E Funkhouser
- G Wingood
- RJ DiClemente
Male sexual dysfunction associated with antiretroviral therapy
- A E Colson
- M J Keller
- P E Sax
- AE Colson