Peter J. Flegg

The impact of chronic hepatitis C virus infection on HIV disease and progression in intravenous drug users.

Objective It is unclear whether co-infection with hepatitis C virus (HCV) can influence HIV related morbidity or mortality, either by accelerating HIV-related disease progression, or by contributing to end stage liver disease. The aim of this study was to examine the effect of HCV infection on the severity and progression of HIV disease in a cohort of Edinburgh intravenous drug users (IDUs). Methods In 240 (47%) out of 508 patients in the Edinburgh IDU cohort both HIV seroconversion dates and anti-HCV serology were available. Demographic variables and HIV-related progression between anti-HCV positive and anti-HCV negative groups were compared. Parameters assessed included clinical endpoints (time of development of significant symptoms attributable to HIV (CDC stage IV), time of development of AIDS, and time of death) and immunological endpoints (time of CD4+ counts dropping below 200/mm3100/mm3 and 50/mm3). Results Two hundred and two out of 240 patients (84%) had positive anti-HCV serology. There was no significant difference in the frequency of clinical and immunological endpoints between the anti-HCV positive and negative groups. Progression analysis from HIV seroconversion to HIV related clinical endpoints indicated that anti-HCV serology was not a significant factor influencing the rate of HIV progression (relative risks (RR) for anti-HCV positive group: seroconversion to CDC IV, 1.01; seroconversion to AIDS, 1.05; seroconversion to death, 0.90). Likewise, HCV serostatus did not significantly affect progression to immunological endpoints (RR for anti-HCV positive group: seroconversion to CD4+ < 200/mm31.04; seroconversion to CD4+< 100/mm31.13; seroconversion to CD4+ < 50/mm3 0.97. Overall mortality from end stage liver failure was 4% in HCV-seropositive patients without AIDS. This suggests that HCV has had a clinically (though not statistically) significant impact on overall survival in this cohort Conclusions This study demonstrates that HCV co-infection does not influence the rate of progression to either clinical or immunological endpoints in our population of HIV-infected drug users. Further data are required to assess the effect of HIV on the progression of HCV-related liver disease.

β2-microglobulin levels in drug users : the influence of risk behaviour

beta 2-microglobulin (beta 2M) levels were measured in 217 Edinburgh drug users to assess their usefulness as a marker for HIV-related disease. Eighty HIV-seronegative drug injectors had significantly higher levels than 100 HIV-seronegative blood-donor controls. Amongst 137 asymptomatic HIV-seropositive drug users, those who were defined as continued drug users had significantly higher beta 2M levels and percentages of CD3+ T lymphocytes with DR Class II expression than non-injecting drug users. beta 2M levels correlated with the percentage of activated DR+ CD3+ T lymphocytes. These findings indicate that changes in beta 2M levels may reflect differences in drug-injecting behaviour and are not influenced solely by HIV status or progression. These changes in beta 2M probably represent differing degrees of immunostimulation resulting from the antigenic challenges afforded by continued or frequent drug injection. It is important to establish normal ranges for beta 2M from HIV-seronegative controls who are matched with respect to risk group and behaviour. All these factors should be taken into account if beta 2M is to be used as a marker of HIV progression.

Clinical features, outcome and survival from cerebral toxoplasmosis in Edinburgh AIDS patients

Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of Edinburgh AIDS patients. All patients were severely immunodeficient at the time of presentation with CD4 count <50 cells/mm 3. Thirteen patients had suffered a previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of patients who are seropositive for toxoplasma and have a CD4 count <50 cells/mm3. It is estimated that at least half of the toxoplasma seropositive patients will develop CTOX if they survive for 21 months after reaching a time in their illness when the CD4 count=50 cells/mm 3. The incidence of CTOX in toxoplasmaseronegative patients with a CD4 count <50 cells/mm 3 is 1.3%. All patients showed improvement on treatment and there was no correlation between clinical or radiological features and patient survival. Those patients unable to tolerate first choice anti-toxoplasma therapy had a significantly shorter survival than the remainder but there was no single therapeutic regimen which conferred a survival advantage. Eighteen patients had died at the time of study and the median survival following diagnosis of cerebral toxoplasmosis was 10 months (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count=50 cells/mm 3 did not differ significantly between those with treated CTOX and a control group who had no toxoplasma infection, suggesting that treatment is reasonably effective. CTOX is a disease associated with severe HIV-related immunodeficiency and, in those with a CD4 count <50 cells/mm 3, occurs more than 35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative patients. Treatment is effective but the outcome of treated disease cannot be predicted from presenting clinical or radiological features. Concomitant space-occupying cerebral pathology is evident in 50% of post-mortem examinations.

Cytomegalovirus disease in AIDS: the Edinburgh experience.

Retrospective analysis of medical records of 557 HIV positive patients (including 113 with AIDS) revealed 17 patients with an antemortem clinical diagnosis of cytomegalovirus (CMV) disease. This group comprised 7 injection drug users (2 male and 5 female) and 10 homosexual men. Males were significantly older than females, and homosexual men were significantly older than drug users at the time of diagnosis of CMV. All 17 patients had evidence of retinitis, and 6 also had evidence of extraocular disease. CMV retinitis was the AIDS defining diagnosis in two patients, and the attack rate of CMV in all AIDS patients progressively increased with time, with a 3-year CMV-free survival of 57%. Fifteen patients with CMV disease had evidence of previous CMV infection (CMV IgG positive), with 7 also having a positive CMV IgM and 10 a positive viral culture. The mean CD4+ lymphocyte count at diagnosis of CMV was 17 cells/mm3, compared with 68 cells/mm3 at diagnosis of AIDS. Therapy was unsatisfactory, often being complicated by marrow suppression. Relapse occurred in 11 patients after initial improvement but despite this only 3 patients died with severe visual impairment. The mean survival after a diagnosis of CMV was 10.5 months. This study confirms that disease caused by CMV is usually a late manifestation of AIDS, and the increasing prevalence among patients with AIDS implies that, the longer the survival, the greater the risk of disease. Frequent fundoscopy in HIV positive patients is of paramount importance particularly in patients who have a CD4+ lymphocyte count of less than 100 cells/mm3.

Beyond the valley of the dolls

As a hospital clinician, I see a great reluctance among some doctors to do anything that might be regarded by patients as undignified. Yet a stay in hospital requires that patients undergo or perform far less dignified processes …

Cytomegalovirus retinitis and AIDS in Edinburgh.

The medical records, retinal drawings and fundus photographs of all patients with cytomegalovirus retinitis (CMVR) and AIDS in Edinburgh between 1986–1992 were reviewed to determine the efficacy of treatment in preserving vision. Ophthalmoscopic features of CMVR were observed in 32 eyes of 24 patients with AIDS, 19 males and 5 females. HIV transmission in this group was by homo/bisexual contact (16), injection drug use (7) and blood transfusion (1). Unilateral blurring was the commonest visual symptom although 9 (38%) patients had no visual symptoms. All patients presented with a corrected visual acuity of 6/12 or better in at least one eye. Following treatment with systemic ganciclovir or foscarnet 16 patients (66%) developed toxic side-effects of therapy and 13 (54%) experienced a recurrence of CMVR. Four (17%) patients developed a retinal detachment in one eye. The mean survival was 8.3 months after the diagnosis of CMVR. At final follow-up, between 2–26 months after the diagnosis of CMVR, 21 (87.5%) patients retained useful vision (6/18 or better) although 3 (12.5%) were effectively blind (less than 6/60). We conclude that with prompt diagnosis and treatment of CMVR vision can be preserved in the majority of cases.

Gonococcal tenosynovitis in two HIV-infected heterosexual men: delayed diagnoses following negative urine nucleic acid amplification testing.

With recent increases in annual gonorrhoea incidence and disproportionately high infection rates amongst men who have sex with men, the clinical picture of disseminated gonococcal infection is changing. We present two cases where consideration of, and investigation for, disseminated Neisseria gonorrhoeae infection provided the answer when routine inpatient diagnostics had been unsuccessful.

Cerebral perfusion in invasive meningococcal disease

I am surprised that the SIGN guidelines (and therefore this summary of them1) make no mention of the importance of adequate cerebral perfusion in those with invasive meningococcal disease. Cerebral perfusion pressure is the difference between the mean arterial pressure (which is usually low from the associated hypotensive shock) and …