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Objective: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts. Methods: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20). Results: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either. Conclusions: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting. Methods: Prospective case-control study. I-NV- 1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV- 1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks. Results: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU. Conclusions: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world. [ABSTRACT FROM AUTHOR]

Seventy-six homosexual or bisexual men underwent two cranial MRI studies at a mean interval of 13 months; 23 were HIV seronegative, 41 seropositive but asymptomatic (Center for Disease Control (CDC) groups II/III), and 12 had AIDS related complex (ARC)/AIDS (CDC group IV). Agreement between two neuroradiologists was rated as very good for assessment of enlargement of ventricles and good for widening of cerebral sulci and the presence of focal lesions. For assessment of serial studies, the agreement was moderate. The prevalence of cerebral atrophy and focal white matter lesions was no higher in the asymptomatic patients (CDC group II/III) than in appropriate seronegative controls. Some patients with ARC/AIDS showed evidence of developing cerebral atrophy during the study period when serial scans were compared. The imaging evidence supports the other data obtained from this cohort, which suggest that no significant CNS involvement occurs in HIV infection before the development of ARC/AIDS. [ABSTRACT FROM AUTHOR]

An empirical approach to treating Pneumocystis carinii pneumonia was adopted in a prospective study of 73 men with antibodies to human immunodeficiency virus 1 (HIV-1) presenting with respiratory problems. At presentation 49 patients (group 1) were thought to have a history, findings at clinical examination, chest radiograph, and arterial blood gas tensions typical of pneumocystis pneumonia, and empirical treatment was begun immediately. Twenty four patients (group 2) were thought to have features not typical of pneumocystis pneumonia. All patients were subsequently referred for bronchoscopy to determine the diagnosis. In group 1 four patients were excluded from the analysis because bronchoscopy was not possible. Of the remaining 45, 42 had pneumocystis pneumonia, which was diagnosed at bronchoscopy in 40, and on the basis of the clinical response to co-trimoxazole in two who had negative results from investigations. Of the three patients without pneumocystis pneumonia, one patient with lymphoid interstitial pneumonitis and Branhamella catarrhalis infection would have failed to respond to empirical treatment. The other two had multiple bacterial pathogens at bronchoscopy; one already had Kaposi's sarcoma and the other would have been misdiagnosed as having AIDS. In group 2 a specific diagnosis was made at bronchoscopy in 21 cases, including pneumocystis pneumonia in seven (all had atypical chest radiographs). In three cases no diagnosis was made and spontaneous recovery occurred. Adopting an empirical approach to treatment for typical pneumocystis pneumonia (group 1) led to the correct treatment in 43 of 45 cases (95%) and would have saved 44 of the 45 of bronchoscopies in this group. Adopting an empirical approach would have caused one patient to be misdiagnosed as having AIDS. Overall, 44 out of 69 bronchoscopies (64%) would have been saved; the specificity for the diagnosis of pneumocystis pneumonia was 85% and the sensitivity was 85%. Adopting an "empirical" treatment policy for typical pneumocystis pneumonia will cause a large reduction in the number of "high risk" bronchoscopies performed. [ABSTRACT FROM AUTHOR]

Background: The hepatitis B virus (HBV) immunisation policy in the United Kingdom includes offering vaccines selectively to those at risk by sexual contact. Among genitourinary medicine (GUM) clinic attenders, homosexual men are offered vaccine, but estimates of the vaccine uptake are required to monitor policy and estimate the possible impact on transmission; heterosexuals are not routinely offered vaccine, but this policy might change if the prevalence was found to be high.Objective: To determine the prevalence of HBV infection and vaccine uptake among patients attending a GUM clinic.Methods: HBV seroprevalence determined by unlinked anonymous testing of consecutive blood samples sent for syphilis serology. Demographic and risk factor data and history of HBV immunization extracted from clinic notes before unlinking. Prevalence data were compared with a population of first time blood donors from the same area.Setting: Open access GUM clinic in central London.Results: Samples were obtained and tested from 441 homosexual and 527 heterosexual men and from 821 women over a 4 month period in 1990. After exclusion of injecting drug users and their sexual partners (n = 30) and HBV carriers attending for follow up (n = 12), the prevalence of antibody to HBV core (anti-HBc) was 38.7% in homosexual men, 5.9% in heterosexual men, and 3.5% in women (50.0%, 6.0%, 3.7% respectively if previous vaccinees were also excluded). The prevalence of HBV surface antigen positivity was 4.2%, 0.60%, and 0.39% respectively after exclusion of vaccinees (chi(2) p < 0.001 for homosexual men versus others). The prevalence of the anti-HBc in first time blood donors was 1.1% (8/749). Among male GUM clinic attenders, the prevalence of anti-HBc was higher in those of non-UK origin or place of birth and/or non-white ethnicity (odds ratios 2.87, 95% CI 1.57-5.24 and 8.06, CI 3.39-19.1, in homosexuals and heterosexuals respectively). In homosexual men anti-HBc prevalence increased with age (OR 1.05, CI 1.02-1.07 for each year) and lifetime number of STDs (OR 6.36, CI 3.77-10.8 for > or = 2 versus < 2) and in clinic reattenders compared with new patients (OR 5.42, 95% CI 3.32-9.16). Among heterosexuals, age was associated with anti-HBc prevalence in women (OR 1.09, CI 1.04-1.12) but not men (OR 0.99, 95% CI 0.95-1.02). There were no other associations in heterosexuals. A history of HBV immunisation in homosexual men was recorded in 13/131 (9.9%) of new patients and 103/305 (33.8%; OR 4.63, CI 2.49-8.60) clinic reattenders.Conclusions: Although higher than a sample of blood donors, the prevalence of serological markers of HBV infection among heterosexuals was low, providing little support for extending HBV immunisation to all heterosexuals attending GUM clinics as a targeted strategy for control of HBV infection. Homosexual men remain at high risk of infection, but many are now being immunised. Efforts to improve compliance with existing vaccine policies in GUM clinics should be encouraged. [ABSTRACT FROM AUTHOR]

Twelve serologically proven cases of non-A, non-B (NANB) hepatitis have been described. The clinical course was mild in 11 patients. One patient, however, presented in portal systemic encephalopathy and required steroid treatment. Nine of the 12 patients continued to exhibit raised transaminase (AST) activities six or more months after the onset of the acute hepatitis. In these immunoglobulin concentrations were normal and autoantibodies were not present in significant titre. Four patients had evidence of previous hepatitis B infection, suggesting that the route of transmission of NANB might be similar to that of hepatitis B virus. A further four patients gave a history which suggests a possible parenteral mode of transmission. Liver biopsies were carried out both in the acute (8 cases) and chronic (6 cases) phases of the disease. Histological findings in liver biopsies covered the whole spectrum of acute and chronic hepatitis and 1 patient had cirrhosis. One notable feature in these biopsies was the presence of fatty changes. [ABSTRACT FROM PUBLISHER]

A randomised controlled trial was conducted in 29 HBV carriers who had been HBs and HBe antigen positive for more than six months. Fifteen patients were treated with ARA-AMP 10 mg/kg/day given as intramuscular injections 12 hours apart for five days followed by 5 mg/kg/day for 23 days. The 14 controls received no treatment. Serum HBV-DNA polymerase, and HBV-DNA decreased in all patients during therapy. Six treated patients lost serum HBV-DNA polymerase, HBV-DNA and HBeAg, HBsAg concentrations decreased, and five developed anti-HBe. One of these six patients lost HBsAg and developed anti-HBs. No such changes were observed in the control group over a similar 18 month period of observation. A four week course of ARA-AMP inhibits HBV replication and in a significant minority of patients this is long lasting and is associated with a reduced level of inflammatory activity in the liver. [ABSTRACT FROM PUBLISHER]

The relationship between the histological diagnosis and serological and tissue markers of HBV replication in 41 Greek and 29 British patients with chronic HBV infection were studied. All the nine Greek and 13 British patients who were HBeAg positive had HBV-DNA in serum and HBcAg expression in the hepatocytes. The majority (73%) of these patients had active liver disease. Forty seven per cent of the Greek and 19% of the British patients who were anti-HBe positive continued to display HBcAg in the liver with or without HBV-DNA detected in serum. All but three of these patients had persistently active liver disease. Continuing inflammatory activity in the liver, however, was also found in 31% of anti-HBe positive patients who had no evidence of HBV replication. In these patients, other factors such as delta agent, NANB viruses, alcohol abuse or an autoimmune reaction initiated by HBV may be contributory. [ABSTRACT FROM PUBLISHER]

The pattern of replicative intermediates seen in the liver of HBe antigen and antibody positive patients was determined. During the phase of HBe antigenaemia the 3.2 Kb species of HBV-DNA (complete HBV genome) is present in the liver but not in the serum. When HBe antigen to antibody seroconversion occurs, either spontaneously or during antiviral therapy, the 3.2 Kb and lower molecular weight intermediates disappear from the liver and the 3.2 Kb band appears transiently in the serum. Integrated HBV-DNA was found in one of 15 patients during the period of HBe antigenaemia and in three of seven patients in the HBe antibody positive phase of the chronic infection before detection of primary liver cell carcinoma. Integrated sequences were found in tumour tissue of two patients with primary liver cell carcinoma who were anti-HBc positive but were absent from the tissues of two patients developing primary liver cell carcinoma at a late stage of autoimmune liver disease. These studies suggest that integration of the HBV genome occurs rarely or in only a small proportion of hepatocytes during the early (HBe antigen positive) phase of infection in Caucasians. They also show that not all primary liver cell carcinomas necessarily contain HBV-DNA. [ABSTRACT FROM PUBLISHER]

Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers. [ABSTRACT FROM PUBLISHER]

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative. [ABSTRACT FROM PUBLISHER]

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity. [ABSTRACT FROM PUBLISHER]

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial. [ABSTRACT FROM PUBLISHER]

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA. [ABSTRACT FROM AUTHOR]