Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.
A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we studied the clinical course of HIV-1 infection in three patients thymectomized for myasthenia gravis and determined the effect of antiretroviral therapy on CD4(+) T cells. We found that five of seven patients had thymus tissue at autopsy and that all thymuses identified had inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two of seven patients also had areas of thymopoiesis; one of these patients had peripheral blood CD4(+) T-cell levels of <50/mm3 for 51 months prior to death. Of three thymectomized patients, one rapidly progressed to AIDS, one progressed to AIDS over seven years (normal progressor), whereas the third remains asymptomatic at least seven years after seroconversion. Both latter patients had rises in peripheral blood CD4(+) T cells after antiretroviral therapy. Most patients who died of complications of HIV-1 infection did not have functional thymus tissue, and when present, thymopoiesis did not prevent prolonged lymphopenia. Thymectomy before HIV-1 infection did not preclude either peripheral CD4(+) T-cell rises or clinical responses after antiretroviral therapy. (+info)
High level inhibition of HIV replication with combination RNA decoys expressed from an HIV-Tat inducible vector.
Intracellular immunization, an antiviral gene therapy approach based on the introduction of DNA into cells to stably express molecules for the inhibition of viral gene expression and replication, has been suggested for inhibition of HIV infection. Since the Tat and Rev proteins play a critical role in HIV regulation, RNA decoys and ribozymes of these sequences have potential as therapeutic molecular inhibitors. In the present study, we have generated several anti-HIV molecules; a tat-ribozyme, RRE, RWZ6 and TAR decoys and combinations of decoys, and tested them for inhibition of HIV-1 replication in vitro. We used T cell specific CD2 gene elements and regulatory the HIV inducible promoter to direct high level expression and a 3' UTR sequence for mRNA stabilization. We show that HIV replication was most strongly inhibited with the combination TAR + RRE decoy when compared with the single decoys or the tat-ribozyme. We also show that the Tat-inducible HIV promoter directs a higher level of steady-state transcription of decoys and inhibitors and that higher levels of expression directly relate to increased levels of inhibition of HIV infection. Furthermore, a stabilization of the 3' end of TAR + RRE inhibitor transcripts using a beta-globin 3' UTR sequence leads to an additional 15-fold increase in steady-state RNA levels. This cassette when used to express the best combination decoy inhibitor TAR + RRE, yields high level HIV inhibition for greater than 3 weeks. Taken together, both optimization for high level expression of molecular inhibitors and use of combinations of inhibitors suggest better therapeutic application in limiting the spread of HIV. (+info)
Tuberculosis outbreaks in prison housing units for HIV-infected inmates--California, 1995-1996.
During 1995-1996, staff from the California departments of corrections and health services and local health departments investigated two outbreaks of drug-susceptible tuberculosis (TB). The outbreaks occurred in two state correctional institutions with dedicated HIV housing units. In each outbreak, all cases were linked by IS6110-based DNA fingerprinting of Mycobacterium tuberculosis isolates. This report describes the investigations of both outbreaks; the findings indicated that M. tuberculosis can spread rapidly among HIV-infected inmates and be transmitted to their visitors and prison employees, with secondary spread to the community. (+info)
A review of statistical methods for estimating the risk of vertical human immunodeficiency virus transmission.
BACKGROUND: Estimation of the risk of vertical transmission of human immunodeficiency virus (HIV) has been complicated by the lack of a reliable diagnostic test for paediatric HIV infection. METHODS: A literature search was conducted to identify all statistical methods that have been used to estimate HIV vertical transmission risk. Although the focus of this article is the analysis of birth cohort studies, ad hoc studies are also reviewed. CONCLUSIONS: The standard method for estimating HIV vertical transmission risk is biased and inefficient. Various alternative analytical approaches have been proposed but all involve simplifying assumptions and some are difficult to implement. However, early diagnosis/exclusion of infection is now possible because of improvements in polymerase chain reaction technology and complex estimation methods should no longer be required. The best way to analyse studies conducted in breastfeeding populations is still unclear and deserves attention in view of the many intervention studies being planned or conducted in developing countries. (+info)
Demographic, clinical and social factors associated with human immunodeficiency virus infection and other sexually transmitted diseases in a cohort of women from the United Kingdom and Ireland. MRC Collaborative Study of women with HIV.
BACKGROUND: Clinical experience suggests many women with HIV infection have experienced no other sexually transmitted diseases (STD). Our objective was to test the hypothesis that a substantial proportion of women with HIV infection in the United Kingdom and Ireland have experienced no other diagnosed STD and to describe the demographic, clinical and social factors associated with the occurrence of other STD in a cohort of HIV infected women. METHOD: Analysis of cross-sectional baseline data from a prospective study of 505 women with diagnosed HIV infection. The setting was 15 HIV treatment centres in the United Kingdom and Ireland. The main outcome measures were occurrence of other STD diagnosed for the first time before and after HIV diagnosis. Data were obtained from interview with women and clinic notes. We particularly focused on occurrence of gonorrhoea, chlamydia and trichomoniasis after HIV diagnosis, as these are the STD most likely to reflect recent unprotected sexual intercourse. RESULTS: The women were mainly infected via heterosexual sex (n = 304), and injection drug use (n = 174). 151 were black Africans. A total of 250 (49.5%) women reported never having been diagnosed with an STD apart from HIV, 255 (50.5%) women had ever experienced an STD besides HIV, including 109 (21.6%) who had their first other STD diagnosed after HIV. Twenty-five (5%) women reported having had chlamydia, gonorrhoea or trichomoniasis diagnosed for the first time after HIV diagnosis, possibly reflecting unprotected sexual intercourse since HIV diagnosis. In all 301 (60%) women reported having had sex with a man in the 6 months prior to entry to the study. Of these, 168 (58%) reported using condoms 'always', 66(23%) 'sometimes' and 56 (19%) 'never'. CONCLUSIONS: Half the women in this study reported having never experienced any other diagnosed STD besides HIV. However, after HIV diagnosis most women remain sexually active and at least 5% had an STD diagnosed which reflect unprotected sexual intercourse. (+info)
Pregnancy, body weight and human immunodeficiency virus infection in African women: a prospective cohort study in Kigali (Rwanda), 1992-1994. Pregnancy and HIV Study Group (EGE).
OBJECTIVE: To study the relationship between human immunodeficiency virus (HIV) infection and body weight in African women during and after pregnancy. METHODS: A prospective cohort study was initiated at the Centre Hospitalier de Kigali in July 1992. Every woman seen at the antenatal clinic and with a gestational age of <28 weeks was offered HIV-1 antibody testing. Comparable numbers of HIV-infected (HIV+) and uninfected (HIV-) women were recruited. At inclusion, socio-demographic characteristics and self-reported pre-pregnancy weight were recorded; height and weight were measured. Each woman enrolled had a monthly follow-up until 9 months after delivery, with a clinical examination including weighing. Three anthropometric indices were used to answer the study objectives: weight, body mass index (BMI), and pregnancy balance. RESULTS: As of April 1994, 101 HIV+ and 106 HIV- women were followed until 5 months after delivery. Weight and BMI during pregnancy were lower in HIV+ women than in HIV- women. After delivery, weight and BMI gains were significantly lower in HIV+ women. Until 5 months after delivery, the mean weight variation was -2.2 kg (standard deviation [SD] = 5.9 kg) in HIV+ women and +0.2 kg (SD = 6.6 kg) in HIV- women (P = 0.007) in comparison to pre-pregnancy weight. Comparisons of the slopes of the weight curves did not show statistical differences throughout the pregnancy, but it did during the post-partum period (P = 0.02). CONCLUSIONS: Our study suggests that HIV infection could impair nutritional status in pregnant women, especially during the post-partum period. Family planning and maternal and child health services including HIV testing and counselling, should consider a nutritional assessment and intervention programme targeted to HIV+ pregnant women. (+info)
Short course antiretroviral regimens to reduce maternal transmission of HIV.(7/30267)
Clinical experience and choice of drug therapy for human immunodeficiency virus disease.
To determine if providers experienced in the management of human immunodeficiency virus (HIV) disease preferred different treatment regimens than providers with less experience, we analyzed data from a national survey of primary care providers' preferred regimens for the management of 30 HIV-related medical conditions. We mailed questionnaires to 999 correct addresses of providers in > 20 cities in the United States in May 1996. We received 524 responses (response rate, 52%). We found a statistically significant association between the number of HIV-infected patients cared for by the provider and the likelihood that the provider would report prescribing highly active antiretroviral therapy and multidrug combinations for treatment of opportunistic infections. Providers with few HIV-infected patients were substantially less likely to report using new therapeutic regimens or new diagnostic tools. We concluded that the preferred regimens of experienced providers are more likely to be consistent with the latest information on treatment for HIV disease than are those of less experienced providers. (+info)