Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome.
Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis. (+info)
Changing epidemiology of hepatitis A in the 1990s in Sydney, Australia.
Surveillance of hepatitis A in residents of Eastern Sydney Health Area identified substantial epidemics in homosexual males in 1991-2 with a peak rate of 520 per 100,000 recorded in males aged 25-29 years, and again in 1995-6, with a peak rate of 405 per 100,000 per year in males aged 30-34 years. During 1994-5 an epidemic was detected among disadvantaged youth associated with injecting drug use; peak rates of 200 per 100,000 per year were reported in males aged 25-29 years and of 64 per 100,000 per year among females aged 20-24 years. The epidemiology of hepatitis A in these inner suburbs of Sydney is characterized by very few childhood cases and recurrent epidemics among homosexual men. Identified risk groups need to be targeted with appropriate messages regarding the importance of hygiene and vaccination in preventing hepatitis A. However, poor access to health services among disadvantaged youth and a constant influx of young homosexual males into these inner suburbs present major challenges to hepatitis A control. (+info)
Coalescent estimates of HIV-1 generation time in vivo.
The generation time of HIV Type 1 (HIV-1) in vivo has previously been estimated using a mathematical model of viral dynamics and was found to be on the order of one to two days per generation. Here, we describe a new method based on coalescence theory that allows the estimate of generation times to be derived by using nucleotide sequence data and a reconstructed genealogy of sequences obtained over time. The method is applied to sequences obtained from a long-term nonprogressing individual at five sampling occasions. The estimate of viral generation time using the coalescent method is 1.2 days per generation and is close to that obtained by mathematical modeling (1.8 days per generation), thus strengthening confidence in estimates of a short viral generation time. Apart from the estimation of relevant parameters relating to viral dynamics, coalescent modeling also allows us to simulate the evolutionary behavior of samples of sequences obtained over time. (+info)
Oral examination: a screening tool for HIV infection?
OBJECTIVE: To estimate the predictive values for HIV infection of diagnosis of oral manifestations of the infection. METHOD: Prevalence of oral manifestations was compared in cross sectional blinded clinical examinations of homosexual men attending a genitourinary medicine clinic. Data were extrapolated to populations in England and Wales based on estimates of the prevalence of HIV infection. RESULTS: Data were analysed for 572 HIV infected and non-infected men (312 and 260 respectively). Positive predictive values for erythematous candidiasis, hairy leucoplakia and pseudomembranous candidiasis were greater than 0.96 at the genitourinary medicine clinic and are estimated to be greater than 0.72 among homosexual men in London. CONCLUSIONS: Clinical diagnoses of mucosal lesions alone are poor predictors of HIV infection but are useful when used in conjunction with a social history to establish if there are risk factors for infection. (+info)
Sexual transmission and prevention of the hepatitis viruses A-E and G.
OBJECTIVES: To assess current knowledge about the potential for sexual transmission of the hepatitis viruses A-E and G and how to prevent any such transmission. METHOD: A search of published literature identified through Medline 1966-June 1998 (Ovid v 3.0), the Cochrane Library and reference lists taken from each article obtained. Textword and MeSH searches for hepatitis A, B, C, D, E, G, delta, GB virus, GBV-C were linked to searches under the textword terms sex$, vaccine$, prevent$, and MeSH subheadings, epidemiology, transmission, prevention, and control. CONCLUSIONS: There is evidence for heterosexual transmission of hepatitis B, C, D, and G and homosexual transmission of hepatitis A-D and G. Condoms are an effective method for preventing transmission by penetrative vaginal or anal sex although spread of types A and B are linked also to oro-anal sex. Hepatitis types A and B can be prevented by pre- and post-exposure active or passive immunisation. There is still some uncertainty about appropriate target groups for pre-exposure vaccination, particularly against hepatitis A. (+info)
Partner notification for gonorrhoea: a comparative study with a provincial and a metropolitan UK clinic.
OBJECTIVE: To compare partner notification practice and outcomes at a provincial and a metropolitan clinic. DESIGN: Prospective study, following standardisation of partner notification policy. SETTINGS: Sheffield Department of Genitourinary Medicine, Royal Hallamshire Hospital and Jefferiss Wing Centre for Sexual Health, St Mary's Hospital, London. SUBJECTS: Consecutive patients with culture positive gonorrhoea between October 1994 and March 1996 who were interviewed by a health adviser. RESULTS: In Sheffield, 235 cases reported 659 outstanding contacts, of whom 129 (20%) were subsequently screened, and 65 (50%) had gonorrhoea. At St Mary's 510 cases reported 2176 outstanding contacts, of whom 98 (5%) were known to have been screened, and 53 (54%) had gonorrhoea. Patient or provider referral agreements appeared more productive in Sheffield, where 60% resulted in contact attendance, compared with 13% at St Mary's. Provider referral was used more frequently in Sheffield, for 44% of referrals, compared with 1% at St Mary's. Multivariate analysis showed that partner notification was less effective for casual and short term (< 7 days) partnerships in both centres, and for homosexual men at St Mary's. CONCLUSION: Partner notification outcomes were better in the provincial setting where contact attendance could be recorded more reliably and provider referral was used more extensively. The high proportion of contacts who remained untraced in both settings indicates the need for complementary screening and prevention initiatives. (+info)
Male homosexuality: absence of linkage to microsatellite markers at Xq28.
Several lines of evidence have implicated genetic factors in homosexuality. The most compelling observation has been the report of genetic linkage of male homosexuality to microsatellite markers on the X chromosome. This observation warranted further study and confirmation. Sharing of alleles at position Xq28 was studied in 52 gay male sibling pairs from Canadian families. Four markers at Xq28 were analyzed (DXS1113, BGN, Factor 8, and DXS1108). Allele and haplotype sharing for these markers was not increased over expectation. These results do not support an X-linked gene underlying male homosexuality. (+info)
Behavioural risk factors for HIV/AIDS in a low-HIV prevalence Muslim nation: Bangladesh.
A review of published and unpublished data indicates the prevalence of high-risk behaviours for HIV transmission in segments of the Bangladeshi population. These include casual unprotected sex, heterosexual as well as between males, prior to and after marriage. Intravenous drug use (IVDU) exists though illicit drugs are more commonly inhaled. There is a fear, however, that inhalers may turn to injecting drugs, as is common in neighbouring countries. The lack of public awareness of HIV/AIDS, and misconceptions about the disease, may contribute to continued high-risk behaviours by segments of the population and, thus, to the spread of HIV. Bangladesh's proximity to India and Myanmar (countries with high HIV endemicity and a rapidly growing number of cases) increases fears of an epidemic in Bangladesh. This proximity will only be a risk factor, however, if high-risk contacts occur between nationals of these countries. (+info)