Maternal hepatotoxicity with nevirapine as part of combination antiretroviral therapy in pregnancy.

OBJECTIVES: To describe the maternal tolerability of nevirapine as part of combination antiretroviral therapy in pregnancy at three HIV centres in Dublin, Ireland and to determine risk factors for development of significant hepatotoxicity. METHODS: A retrospective study was carried out of all women prescribed nevirapine as part of combination antiretroviral therapy in pregnancy at three HIV centres in Dublin, Ireland (October 2000 to February 2003). Toxicities experienced were graded according to the Division of AIDS toxicity guidelines for adults. Statistical analysis was performed to determine whether there were differences between those that did and those that did not experience significant hepatotoxicity. RESULTS: A total of 123 women initiated nevirapine as part of combination antiretroviral therapy in the study period. Eight women developed significant hepatotoxicity, including two women who died from fulminant hepatitis. Women who experienced more severe hepatotoxicity had higher pretreatment CD4 counts (P=0.01). CONCLUSIONS: In this cohort, women who experienced more severe hepatotoxicity had higher pretreatment CD4 counts, lending additional weight to the need for caution in using nevirapine as part of combination antiretroviral therapy in women not requiring antiretroviral therapy for their own health.

Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users.

Administration of nevirapine to HIV-infected injection drug users who also receive methadone results in a significant reduction in methadone exposure after 7-10 days of therapy. Many patients require an increase in methadone dose to counteract this effect.

The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz.

AIMS: Methadone is predominantly metabolized by cytochrome P450 3A4 and the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is a recognized inducer of this enzyme. We evaluated the pharmacokinetics of methadone in the presence and absence of efavirenz when administered to HIV infected patients with a history of injection drug use (IDU). METHODS: Eleven patients on stable methadone maintenance therapy, due to commence antiretroviral therapy (ART), participated in this study. Steady state methadone kinetic profiles were obtained on two occasions 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h post dosing. Following centrifugation, separated plasma was heated at 58 degrees C for 30 min to inactivate HIV and stored at -80 degrees C until methadone analysis by high performance liquid chromatography. RESULTS: When combined with efavirenz there was a marked decrease in the maximum plasma concentration (Cmax) of methadone from 689 (range 212-1568) to 358 (range 205-706) ng ml(-1), P = 0.007 : 95% confidence interval (CI) 112-549. The mean area under the methadone concentration curve 0-24 h (AUC(0,24 h)) was also significantly reduced from 12341 (range 3682-34147) to 5309 (range 2430-10349) ng ml(-1) h in the presence of efavirenz, P = 0.012 : 95% CI 1921-12143. Nine patients described symptoms of methadone withdrawal and received a dose increase. Although methadone AUC(0,24 h) was reduced by over 50% following efavirenz the mean increase in methadone dose required was 22% (range 15-30 mg). CONCLUSION: The inclusion of the NNRTI efavirenz in once daily ART for HIV patients with a history of IDU receiving methadone maintenance results in a significant reduction in methadone plasma concentrations mediated by enzyme induction. It is important to distinguish efavirenz neurological effects which were observed between days 1-5 of therapy from symptoms of methadone withdrawal which occurred from day 8 onwards. The dose of methadone was adjusted by increments of 10 mg to counteract the efavirenz inducing effect.

Antiretroviral therapy for drug users.

Injection drug use represents the primary risk factor for up to 40% of patients with HIV infection. Physicians are generally reluctant to prescribe antiretroviral therapy (ART) for these patients due to possible poor adherence, and the potential for complex drug interactions to occur. Providing daily observed ART in conjunction with methadone maintenance therapy (MMT) has significantly improved accessibility of ART for many drug users. Knowledge of potential drug interactions between methadone, ART, and both legally and illegally prescribed drugs has permitted such interactions to be anticipated and either avoided or treated appropriately. Optimizing ART for drug users therefore demands a multidisciplinary approach from medical, clinical pharmacology and psychiatric services.

Survival with AIDS in Ireland.

OBJECTIVE: To analyse the pattern of survival for patients diagnosed with AIDS in Dublin. METHODS: Data on 193 patients visiting the Department of Genitourinary Medicine of a Dublin Hospital, over a period of 7 years with AIDS, were analysed, and survival patterns were investigated. RESULTS: The cumulative probability of survival for the cohort was 69.0 +/- 3.3% at 1 year and 6.5 +/- 2.5% at 5 years. Median survival was 576 days. Year of diagnosis and disease group to which the patient belonged at diagnosis had a significant influence on the survival of the cohort (P < 0.0006 and P < 0.02, respectively). Age group, disease group, and year of diagnosis showed significant differences between strata (P < 0.01, P < 0.002, and P < 0.04, respectively). Patients aged 35-39 years showed longer median survival times (715 days) than all other age groups (median survival = 547 days; P < 0.04). Patients whose disease group at diagnosis was opportunistic disease(s) alone (Centers for Disease Control 1987 criteria, stage IV group C1) had a significantly longer median survival (672 days) than all others (median survival 281 days; P < 0.0002). Survival did not differ significantly by sex or risk group alone, nor did it differ significantly by manifestation of disease when grouped according to recognised criteria. Treatment with antiretroviral therapy had a significant influence on the survival of the cohort (P < 0.0002), and the treatment group showed a significant difference between strata (P < 0.0002). This result must be qualified by the fact that, first, 11 of the 26 patients not receiving therapy died within 1 month of diagnosis and people who survived longer had a greater chance of beginning treatment, and that, secondly, criteria for antiretroviral therapy allocation were not entirely clear. CONCLUSIONS: The overall survival time found by this study is comparable to that found in other studies in developed countries of the survival of persons with AIDS. Patterns of survival for age groups and manifestation of disease show some contrasting features, mainly owing to the demographic profile of the patients and the high proportion of intravenous drug users.

Renal ultrasonic findings in sulphadiazine-induced renal failure.

The increased incidence of cerebral toxoplasmosis in AIDS has led to a resurgence in the use of sulphadiazine. One complication of this is acute renal failure secondary to sulphadiazine-induced crystalluria. Three cases are described which demonstrate a spectrum of ultrasound findings ranging from echogenic foci in the renal parenchyma to echogenic material in both dilated and non-dilated collecting systems. In patients with AIDS having sulphadiazine treatment, these ultrasonic findings suggest that sulphadiazine is the cause of the renal failure.

An evaluation of percutaneous endoscopic gastrostomy feeding in AIDS.

Between October 1991 and October 1993, 17 AIDS patients (14 intravenous drug users, 3 sexually acquired) were commenced on percutaneous endoscopic gastrostomy (PEG) feeding in St James's Hospital. Indications were progressive weight loss related to severe anorexia, persistent oesophageal candidiasis (5) and absence of gag reflex (1). Two patients requested PEG tube removal after one week because of crampy abdominal pain without peritonitis. Five patients died from AIDS related infections within 6 weeks of PEG insertion. Ten patients were followed up for > 2 months (mean 5.2 months, range 2.5-15.5 months). In these 10 patients, 1 patient developed a PEG site infection which responded to topical antibiotics. There were no other complications. There was a significant (P < 0.001) increase in energy and protein intake at 2 months. Variant degrees of weight gain occurred in all patients (mean 2.6 kg) (P < 0.01). Small but significant increases in other anthropometric variables occurred. Patients who died within 6 weeks of PEG insertion were older, and had a lower serum albumin than the group who survived > 2 months (P < 0.01). A self-administered questionnaire demonstrated that the majority of patients found PEG feeding acceptable and preferable to nasogastric (NG) feeding.

Cervical cytological screening in HIV-infected women in Dublin--a six-year review.

A retrospective study of the results of cervical cytological screening of HIV-infected women attending an inner city ambulatory HIV clinic over a 6-year period between 1987 and 1992 was carried out. During this time a total of 165 HIV-infected women attended for management of their HIV disease. The results of cervical cytological specimens (smears) were available in 136 (82.4%) women. The risk categories for HIV infection of these 136 women were intravenous drug use 110 (80.9%), heterosexual sex 24 (17.6%) and undetermined 2 (1.5%). Eighty-five (62.5%) of the 136 women were classified CDC group 2, 30 (22%) CDC group 3, and 21 (15.5%) CDC group 4 at the time of initial cytological screening. Forty-one (30.1%) women had mild dysplasia/CIN 1, 21 (15.4%) had moderate dysplasia/CIN 2 and 17 (12.5%) had severe dysplasia/CIN 3. The overall prevalence of dysplasia/CIN was 58.1%. Twenty-seven (34.2%) of the women with dysplasia/CIN had cytological evidence of human papillomavirus infection. No association between the clinical stage of HIV disease and the presence or degree of dysplasia/CIN was demonstrated. Women with cytological evidence of CIN were significantly more likely to have had genital warts than those with no evidence of CIN (OR 3.1, CI 1.1-10). In those women with cervical dysplasia who underwent colposcopic examination, CIN was confirmed in a high proportion of cases. The default rate from colposcopy, however, was high (35.4%).

Concomitant HIV and mycobacterial infection in Ireland, 1987-92.

A six-year retrospective review of concomitant HIV and mycobacterial infection in the Republic of Ireland is presented. A total of 42 culture proven mycobacterial infections were seen in 40 different HIV-infected patients. There were 24 infections with Mycobacterium tuberculosis (M.tb) and 18 infections with mycobacteria other than tuberculosis (MOTT), a significantly higher rate of MOTT infections in Ireland compared to a study from 1962-1981. The detection rate for all mycobacterial infections had an annual upward trend with a 4-fold increase between 1987 and 1992. In homosexuals, MOTT infections occurred more frequently than M.tb, while the reverse was true for IVDUs. Twenty per cent of the infections were seen in patients recently incarcerated. Relapse of tuberculosis occurred in 42.9% (3/7) of non-compliant patients, 2 of whom developed rifampin-resistant strains of M.tb. No patient compliant to their regimen had a relapse in disease. The overall survival of patients after diagnosis of M.tb was significantly better than those with MOTT infections, with respective one-year survival rate of 79% and 36% (log rank test, P = 0.006).

Contraceptive practices in HIV seropositive females in Ireland.

A questionnaire was administered to a cohort of 130 HIV seropositive women attending the Department of Genitourinary Medicine, St James's Hospital, Dublin, in order to establish their current contraceptive practices. Forty (42%) of the sexually active women did not use reliable contraception; 55 (57%) used a method reliable in fertility control only, and 21 (22%) used a method reliable in terms of both partner and congenital transmission. The intravenous drug users were less likely to use reliable contraception, 9 (39%), in comparison to the heterosexual group 14 (70%), P < 0.05. The heterosexual group were more likely to use condoms consistently, 7 (35%) in comparison to one (4%) of intravenous drug users, P < 0.02. Nineteen children, 3 borne to heterosexual mothers and 16 borne to intravenous drug-using mothers were HIV seropositive after 18 months.

AIDS, i.v. drug use and mycobacterial disease: the Dublin experience.

In the period 1980-1985, we treated 1641 patients for tuberculosis of whom two were known to be intravenous drug users (IVDU) and none had HIV infection. Of the next 1000 patients treated for tuberculosis (January 1986-December 1989), six were HIV-negative intravenous drug users (IVDU), 18 patients were HIV-positive (12 IVDU; six homosexual/bisexual). Statistical analysis (chi 2) showed a numerically small but statistically significant (P < 0.00001, d.f. = 1, chi 2 = 20.38) increase in intravenous drug users with a diagnosis of tuberculosis. The HIV-positive patients who completed treatment responded well to anti-tuberculous drugs. The importance of tuberculosis in the context of HIV infection is that it is preventable, treatable and is the only bacterial infection to which HIV subjects are prone which can be readily transmitted to a non-HIV infected subject.

Toxoplasma pneumonitis: fatal presentation of disseminated toxoplasmosis in a patient with AIDS.

Toxoplasma gondii infection is an uncommon cause of pneumonitis in patients with acquired immune deficiency syndrome (AIDS). We report a case of fatal pulmonary toxoplasmosis, which clinically resembled Pneumocystis carinii pneumonia (PCP). Conventional diagnostic methods for toxoplasmosis lack sensitivity. Bronchoscopy and histological evaluation of transbronchial biopsy specimens failed to identify the infecting organism. At autopsy there was evidence of disseminated infection.

Fournier's gangrene of scrotum in a patient with AIDS.

Fournier's gangrene of the scrotum, a form of necrotising fasciitis, is a rare but potentially fatal disorder. Predisposing conditions include chronic alcoholism and diabetes mellitus, possibly as a result of impaired immunity. Fournier's syndrome, occurring in a patient with AIDS, is described.

Measuring treatment compliance of men with non-gonococcal urethritis receiving oxytetracycline combined with low dose phenobarbitone.

Of 62 men with non-gonococcal urethritis who entered a study to assess compliance with treatment with oxytetracycline, only 33 could be evaluated. Traditional methods (interview and the absence of oxytetracycline in the urine) showed incomplete compliance in nine. Use of low dose phenobarbitone as a pharmacological marker showed incomplete compliance in a further five patients. In addition, phenobarbitone concentrations gave information on the extent to which individual patients had omitted treatment and provided direct, as opposed to circumstantial, evidence of good compliance by most (18) of those studied. Only three of the 33 patients whose compliance was assessed had evidence of continuing infection at follow up, and there was evidence of incomplete compliance in only one of these patients.

Sexually transmitted infections in adolescent girls.

Two hundred and ten adolescent girls in residential care with an age range of 12 to 16 years were screened for sexually transmitted infections. The incidences of infection with Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis were 13.7%, 16.2%, and 16.0% respectively. Pelvic inflammatory disease was identified in 16.4% of those with C trachomatis or gonococcal infection. The high morbidity from sexually transmitted disease in these adolescent girls reinforces the need for screening similar at risk teenagers.

Prevalence of chlamydial infection in acute epididymo-orchitis.

The prevalence of sexually transmitted infection was studied in 40 men presenting with acute epididymo-orchitis in Leeds. Chlamydia trachomatis infection was identified in 13 of 29 men (45%) aged under 35 years. Neisseria gonorrhoeae was isolated from four of these 13 men with chlamydial urethritis. C trachomatis was isolated from the urethra of only one of 11 men (9%) aged over 35. Appreciable bacteriuria was found in six of these 11 men (55%). Noting details of sexual history and screening for sexually acquired pathogens is advocated in younger men with acute epidiymo-orchitis.