Showing papers in "AIDS in 1994"
TL;DR: There are individuals with long-term HIV infection who appear clinically and immunologically healthy 10–15 years after HIV seroconversion, with stable CD4+ counts, and Lack of exposure to STD or recreational drugs does not appear to explain the delayed course of disease progression in HLP.
Abstract: Objective:To identify and describe a subgroup of men infected with HIV for 10–15 years without immunologic progression, and to evaluate the effect of sexually transmitted diseases (STD) and recreational drug use on delayed HIV disease progression. Design: Inception cohort study. Setting: Municipal S
403 citations
TL;DR: In this paper, the authors present a study which critically reviews the scientific literature on AIDS prevention programs in an attempt to determine the extent to which behavioral intervention research has demonstrated the efficacy of methods for risk behavior reduction.
Abstract: This paper presents a study which critically reviews the scientific literature on AIDS prevention programs in an attempt to determine the extent to which behavioral intervention research has demonstrated the efficacy of methods for risk behavior reduction. Its focus is on addressing the three most critical questions in intervention research: 1) have AIDS prevention programs had long-term success in behavior change; 2) what recommendations can be made to program developers; and 3) where should HIV prevention research be heading.
243 citations
TL;DR: Influenza vaccination should not be administered to HIV-infected individuals with CD4+ counts <100×106/l; pneumococcal vaccination can be offered to all HIV- Infected individuals and a tetanus toxoid booster should be administered when indicated.
Abstract: OBJECTIVE To establish when the formation of antibodies against T-lymphocyte-dependent and -independent antigens is impaired during HIV infection. DESIGN Prospective study on antibody formation before and 30 days and 60 days after vaccination with tetravalent influenza vaccine, tetanus toxoid and pneumococcal vaccine; booster with influenza vaccine was administered 30 days after initial vaccination. SETTING Outpatient clinic of University Hospital Leiden. PARTICIPANTS Fifty-one HIV-infected individuals and 10 healthy controls. RESULTS In HIV-infected individuals with or = 300 x 10(6)/l yielded more individuals with protective antibody titres. Thirty days after vaccination, protective antibody titres against the four influenza strains had been achieved in 24% of all HIV-infected individuals for A/Beijing (H3N2) (controls, 90%), 59% for A/Taiwan (H1N1) (controls, 80%), 18% for B/Beijing (controls, 30%) and 37% for B/Panama (controls 90%). Booster vaccination after 1 month did not increase antibody levels. Anti-tetanus toxin antibody formation, which is also T-lymphocyte-dependent, was correlated with the number of CD4+ lymphocytes. After pneumococcal vaccination (T-lymphocyte-independent), normal antibody formation was observed in HIV-infected individuals, including those with low CD4+ counts. CONCLUSIONS Influenza vaccination should not be administered to HIV-infected individuals with CD4+ counts < 100 x 10(6)/l; pneumococcal vaccination can be offered to all HIV-infected individuals and a tetanus toxoid booster should be administered when indicated.
239 citations
Journal Article•
TL;DR: Genetic diversity, divergence, or variation within or between subtypes, genotypes, or isolates, as well as HIV transmission and infections in Japan, Australia, Cambodia, China, Taiwan, Philippines, Malaysia, Myanmar, and in states created out of the former Soviet Union are discussed.
Abstract: The human immunodeficiency virus (HIV) was introduced readily into Asia and has quickly spread between Asian states through both parenteral and sexual modes of transmission. Only 1 year after Thailands epidemic wave among intravenous drug users (IDUs) in 1988 the virus spread to the adjacent Myanmar and Malaysia and another year later IDUs were infected in parts of India and China bordering Myanmar. Several methods can be used to quantify the genetic diversity divergence or variation within or between subtypes genotypes or isolates. Consensus sequences representing the most common nucleotide in the genome are often generated for comparison. 8 subtypes A through F H and O have been described for HIV-1 based on the genetic similarities and differences in the env gene or viral envelope. Subtype A and D have been found primarily in central and western Africa. Subtype B is predominant in Europe the Western hemisphere Japan and Australia. Subtype C has been found mostly in southern Africa the Central African Republic and India. Subtype E was first identified in Thailand and recently in the Central African Republic. Subtype F has been found in Romania and is a rare variant in Brazil. Isolates from Gabon and the Russian Federation were designated subtype H. An "outlier" subtype O containing 2 human and 2 chimpanzee isolates has been identified in Cameroon and Gabon. Sequencing of the relatively conserved gag gene of geographically diverse HIV-1 isolates yielded a classification with 7 subtypes A-D and F-H. Other topics discussed include genome characterization comparison with foreign isolates segregation by mode of transmission and biologic properties of HIV-1 variants in Thailand; regional diversity of HIV-1 subtypes and substantial spread of HIV-2 in India; as well as HIV transmission and infections in Japan Australia Cambodia China Taiwan Philippines Malaysia Myanmar and in states created out of the former Soviet Union.
210 citations
TL;DR: In HIV-1 infection activated CD3+CD28− T cells accumulate but are unresponsive to mitogens and anti-CD28, which appears to represent terminally differentiated effector cells which fail to respond to further stimuli because of the absence of a CD28 second signal.
Abstract: Objectives and design: The expression of the accessory molecule CD28 was compared in various populations of T and natural killer (NK) cells from HIV-1-negative and HIV-1-positive individuals and correlated with activation using mitogens in vitro.Methods: Multiparameter flow cytometric analysis using combinations of CD3 CD28 and other markers was performed together with absolute cell counting in peripheral blood. Blast transformation and proliferative responses were also quantitated using the Cytoron(absolute) after stimulation with phytohaemagglutinin (PHA) and anti-CD3. CD28- cells were also purified to confirm the observations.Results: In HIV-1-negative individuals >90% of CD3+ T cells were CD28+ and responded to stimulation, while CD3- CD16+ CD57+ NK-like cells were CD28- and failed to respond. In HIV-1-positive individuals the expression of CD28 was greatly reduced and the proportion of CD3+CD28- T cells expanded. CD8 lymphocytosis was caused entirely by the accumulation of CD28- T cells and many of these expressed activation markers human lymphocyte antigen-DR, CD38 and CD45RO on their membrane and molecules such as TIA-1 and perforin, associated with cytolytic function, in their cytoplasm. The strong positive correlation (r = 0.66) between the lack of CD28 expression and the poor proliferation from HIV-1-positive individuals was confirmed by demonstrating that only CD28+ cells transformed into lymphoblasts and proliferated. Although the CD28- including CD3+ T cells transiently expressed CD25 (interleukin-2Ralpha), they did not undergo blastogenesis or activation measured by bromodeoxyuridine uptake and died after 3-4 days in culture. These observations were confirmed in costimulation experiments with anti-CD2 and anti-CD28.Conclusion: In HIV-1 infection activated CD3+CD28- T cells accumulate but are unresponsive to mitogens and anti-CD28. These cells appear to represent terminally differentiated effector cells which fail to respond to further stimuli because of the absence of a CD28 second signal.
206 citations
TL;DR: The 1985–1990 HIV seroconversion rate in IVDU was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy), and a decline in HIV serconversion coincided with changes in risk behavior.
Abstract: OBJECTIVE: To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990 DESIGN: Observational study SETTING: All methadone maintenance and 21-day methadone detoxification programs in San Francisco PARTICIPANTS: A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters') MAIN OUTCOME MEASURES: HIV seroconversion rates, risk factors for seroconversion, and changes in behavior RESULTS: The HIV seroconversion rate in repeaters was 19% per person-year (ppy) of follow-up [21% in women versus 17% in men (not significant); 4% in African Americans versus 1% in whites (P = 0006); 39% ppy in the first third of the study, 12% in the second (P = 0007), and 19% in the last (not significant)] Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 26; P = 002], use of shooting gallery ever (HR = 29; P = 002), and less than 1 year (lifetime) in methadone maintenance (HR = 27; P = 002) Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10% Bleach use rose to 75% of needle-sharers CONCLUSIONS: The 1985-1990 HIV seroconversion rate in IVDU (19% ppy) was comparable to that in San Francisco cohorts of homosexual men (14% ppy) A decline in HIV seroconversion coincided with changes in risk behavior Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy
187 citations
TL;DR: HIV-1 proviral DNA can be demonstrated by IS-PCR in seminal mononuclear cells and sperm from certain HIV-1-infected men and the role played by proviralDNA in these cells in the sexual transmission of this retroviral agent will require further study.
Abstract: ObjectiveSexual transmission is a major mode of the spread of HIV-1, although the cellular and molecular mechanisms are poorly defined. In this study, we sought to assess the cellular reservoirs of HIV-1 proviral DNA in the semen of HIV-1-infected men.Design and methodsAn in situ polymerase chain re
173 citations
TL;DR: Findings on a limited number of viruses suggest extensive env gene diversity of HIV-1 strains from Cameroon, and could have implications for vaccine development in Africa.
Abstract: The only two HIV-1 strains (ANT70 and MVP5180) reported to date from Cameroon are members of the outlier clade (group O). In this study the authors assessed the prevalence of group O viruses and other HIV-1 subtypes in Cameroon. A phylogenetic analysis of 18 HIV-1 strains isolated from seropositive individuals from Yaounde and Douala Cameroon were part of this design. A 900 base-pair fragment of the env gene coding for V3 V4 V5 and the beginning of gp41 of 17 out of 18 HIV-1 isolates from Cameroon was amplified cloned and sequenced using polymerase chain reaction. A phylogenetic tree was constructed. The overall env nucleotide sequence divergence among the Cameroon isolates ranged from 6.1 to 27.5%. In a phylogenetic tree six subtypes were identified when compared with 23 reference strains of different geographic origin. Of these 17 Cameroonian strains 11 (61%) were of subtype A of which the interpatient distances at the sequence level varied from 6.1% to 18.3% (average 11.9%). Three (17%) strains were of subtype F and the other three strains (6% each) belonged to subtypes B E and H respectively. The remaining isolate was classified as belonging to group O on the basis of the sequence of part of the pol gene. A very broad spectrum of different tetrameric amino-acid sequences was observed at the apex of the V3 loop. Eleven strains contained the tetrameric globally predominant GPGQ sequence at the tip of the V3 motif. Two strains had the GPGR sequence typical of the American and European HIV-1 strains. The remaining tetrameric sequences included GPGS GSGQ GRGQ and GLGR. These findings on a limited number of viruses suggest extensive env gene diversity of HIV-1 strains from Cameroon and could have implications for vaccine development in Africa. (authors)
170 citations
165 citations
TL;DR: In the course of HIV disease mitogen-stimulated IL-2 production decreased, spontaneous and stimulated IL-6 production and spontaneous IL-10 secretion increased, and a switch from a type 1 to a type 2 response occurs in HIV infection.
Abstract: ObjectiveTo study the TH1->TH2 cytokine switch, thought to occur during the progression of HIV infection.DesignWe investigated interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cul
160 citations
TL;DR: KS-like lesions were obtained by injecting cell-free secreted products, suggesting that KS is a 'self-propagating' proliferative lesion caused by a cytokine imbalance and not a true neoplasm, and metalloproteinase inhibitors could be potential therapeutic agents for KS.
Abstract: Objective:To determine the neoplastic nature of Kaposi's sarcoma (KS). A highly vascularized lesion, KS is frequently associated with AIDS, indicating HIV products may be involved.Design and methods:We determined the angiogenic properties of KS cell-secreted products and the HIV-1-tat gene product i
TL;DR: The increasing risk with age was similar in hemophiliacs and homosexual men, suggesting that age is an endogenous host factor and can be incorporated into newly developed backcalculation models to estimate HIV infection incidence by age group from age-specific AIDS surveillance data.
Abstract: ObjectiveTo estimate the age-specific relative risk of progression from HIV seroconversion to onset of AIDS in hemophiliacs and homosexual men.DesignProspective follow-up data from HIV seroconversion to AIDS was analyzed for hemophiliacs in the Multicenter Hemophilia Cohort Study and for homosexual
TL;DR: Mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1- Infected patients.
Abstract: Objective: to compare survival of patients infected with HIV-1 and HIV-2. Design: longitudinal follow-up of 175 HIV-1-and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. Methods: survival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. Results: the overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (Cl), 0.49-0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% Cl, 0.43-0.94), and for three strata of [beta]2-microglobulin levels 0.60 (95% Cl, 0.42-0.84). Conclusion: mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients
TL;DR: The isolated position of HIV-positive individuals may serve as a barrier to HIV transmission and may account for the lack of diffusion of HIV in heterosexual populations in this region.
Abstract: OBJECTIVE To determine how heterosexuals at risk for HIV infection interconnect in social networks and how such relationships affect HIV transmission. DESIGN Cross-sectional study with face-to-face interviews to ascertain sociosexual connections; serologic testing. PARTICIPANTS Prostitute women (n = 133), their paying (n = 129) and non-paying (n = 47) male partners; injecting drug users (n = 200) and their sex partners (n = 41). Participants were recruited in sexually transmitted disease and methadone clinics, an HIV-testing site, and through street outreach in Colorado Springs, Colorado, USA. MAIN OUTCOME MEASURES Reported behaviors, risk perceptions, sociosexual linkages, and HIV prevalence. RESULTS Respondents were well informed, but reported engaging in high-risk behaviors frequently. Nevertheless, over 70% of respondents perceived themselves to be at low risk for HIV infection. The 595 respondents identified a social network of 5162 people to which they belonged. Network analytic methods indicated 147 separate connected components of this network; eight of the 19 HIV-positive individuals in the network were located in smaller components remote from the largest connected component. CONCLUSION The isolated position of HIV-positive individuals may serve as a barrier to HIV transmission and may account for the lack of diffusion of HIV in heterosexual populations in this region. Network analysis appears useful for understanding the dynamics of disease transmission and warrants further development as a tool for intervention and control.
TL;DR: These results demonstrate the profound impact that the HIV-1 epidemic has on adult mortality in a rural area of Uganda where theAIDS prevalence and incidence rates in adults are 8 and 1%, respectively.
Abstract: The authors sought to determine the incidence of HIV-1 infection and HIV-1-associated mortality in a rural Ugandan population. This prospective cohort study consisting of the population (de jure census 9820) of a cluster of 15 villages in Masaka District southwest Uganda was enrolled between 1989 and 1990 through a demographic and medical survey. The HIV-1-seroprevalence rate was 4.8% for all ages combined and 8.2% for those aged 13 years or more. The survey was repeated after 1 year. The 1-year HIV-1 incidence rate among adults was 1% (9.2 per 1000 person-years of observation; 95% confidence interval [CI] 5.5-12.9). A total of 84 deaths were observed. In adults half of all deaths (31 of 60) were in HIV-1-seropositive individuals. The age-adjusted overall mortality rate ratio for HIV-positive adults compared with HIV-negatives was 20.8 (95% CI 12.0-35.7). In the 13-44 age group the corresponding rate ratios for men women and both sexes combined were 16.3 108.9 and 58.7 respectively. The HIV-attributable mortality fractions i.e. the proportion of deaths that would have been avoided in the absence of HIV were 44 50 and 89% for adult men adult women and adults aged 25-34 years (both sexes combined) respectively. The 1-year progression to death among HIV-1-seropositive adults was 10.3%. These results demonstrate the profound impact that the HIV-1 epidemic has on adult mortality in a rural area of Uganda where the HIV-1 prevalence and incidence rates in adults are 8 and 1% respectively. (authors)
TL;DR: HIV is the leading cause of adult death in Rakai, Uganda, and its effects on mortality are particularly marked in the most economically active sectors, resulting in continued rapid population growth.
Abstract: This study sought to examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. A one-year follow-up (1990-1991) was undertaken in a population-based rural cohort set in the Rakai District. There was an annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters and these subjects provided yearly HIV serological samples as well as behavioral and health information. The main outcome measure was mortality in HIV-infected and uninfected persons. Mortality among HIV-seropositive adults aged >or= 15 years of 118.4/1000 person-years (PY) was substantially higher than in HIV-seronegative adults (12.4/1000 PY; relative risk [RR] 9.5; 95% confidence interval [CI] 6.0-14.9). Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111/1000 live births; RR 1.9; 95% CI 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and in this cohort with higher education non-agricultural occupation and residence in roadside trading centers. The authors estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined district HIV attributable mortality is 28%. The authors conclude that HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However the overall crude birth rate in the district (45.7/1000 population) remains higher than the crude death rate (28.1/1000 population) resulting in continued population growth. (authors)
TL;DR: Since clinical trials call for a study population with a high seroincidence rate attributable primarily to the sexual transmission of HIV, prostitutes are the logical choice of subjects; sex workers are, however, the women most vulnerable to physical and economic exploitation.
Abstract: The development and testing of safe effective and affordable microbicidal products for women at risk of human immunodeficiency virus (HIV) raise complex scientific ethical and political issues. Ideal would by range of products (gels foams suppositories) that protect against HIV and other sexually transmitted diseases without impairing conception. This in turn requires the development of vaginal compounds that prevent the attachment of HIV-infected lymphocytes to epithelial surfaces the secretion of virus from these cells or the uptake of the virus by the mucosal epithelium with minimal cell membrane disruption. Problematic would be the design of a Phase III effectiveness trail that distributes the burdens and benefits of research equitably and provides controls with an alternate means of protection against HIV while maintaining scientific rigor. Since clinical trials call for a study population with a high seroincidence rate attributable primarily to the sexual transmission of HIV prostitutes are the logical choice of subjects; sex workers are however the women most vulnerable to physical and economic exploitation. Womens input will be essential at each stage of development and testing and such consultation can provide valuable feedback on method of application and timing of insertion. Finally public-sector organizations must assume a leadership role in the coordination of the development of HIV prevention technologies.
TL;DR: HIV-1 infection appears to have an effect on the central nervous system dopaminergic systems, as reflected in levels of CSF dopamine, in a prospective, longitudinal study of the neurological complications of AIDS.
Abstract: BackgroundIncreasing evidence suggests significant involvement of the basal ganglia in patients with HIV-1 infection.ObjectiveTo study the effect of HIV-1 infection on cerebrospinal fluid (CSF) dopamine levels.DesignCSF dopamine levels were measured by high-performance liquid chromatography.SettingA
TL;DR: It is concluded that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China.
Abstract: The authors investigated the prevalence of drug injection among drug users the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IVDUs) and the extent of heterosexual transmission of HIV among IVDUs and their spouses in southwest China. Findings are based upon a cross-sectional HIV seroprevalence and behavioral survey in the rural counties Ruili Longchuan and Luxi of Yunnan province in southwest China. 860 drug users were recruited in randomly selected communities along with a random sample of 62 wives of HIV-infected IVDUs. 33% of the 860 drug users reported injecting drugs. Of the 282 who injected drugs 82% began IV drug use after 1988 and 64% injected drugs at least once daily. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. 49% overall tested HIV-seropositive. HIV seropositivity was independently correlated with a longer history of drug injecting daily injecting frequent needle-sharing being younger and living in Ruili county. None of the 62 wives of HIV-positive IVDUs used condoms during sex and 10% tested HIV-positive. The introduction of HIV into drug-using communities and the rapid increase in heroin injecting in the population appear to have triggered an explosive HIV epidemic among IVDUs in the region. It is recommended that AIDS prevention efforts begin immediately with a focus upon discouraging the shift from opium smoking to heroin injecting needle-sharing and unprotected sex among drug users and their partners.
TL;DR: Among young Rwandan women, the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection, and interventions should focus on young teenagers before they become sexually active.
Abstract: The authors sought to determine the incidence of HIV-1 infection and associated risk factors among young seronegative and sexually active women in a mixed rural and urban population in southern Rwanda. This prospective cohort study was conducted between October 1991 and April 1993 the authors completed a 2-year follow-up survey among HIV-1 seronegative woman aged < or = 30 years at the time of their initial HIV-1 screening during pregnancy. All women aged < or = 25 years and a randomly selected sample of 26-30 year olds were invited to participate from five prenatal clinics in the Butare region. The interview focused on potential risk factors for HIV-1 acquisition during the 2-year interval between blood collection. Out of 1524 women selected 1150 (75%) participated in the follow-up survey. The 2-year incidence of HIV-1 infection was 2.7% (95% confidence interval [CI] 1.8-3.9). Teenage women were at the highest risk (incidence 10.5%; 95% CI 5.2-19.4) with incidence leveling off with increasing age (p < 0.001). Women who began sexual activity recently were also at higher risk; the lowest risk category consisted of women aged 26-30 years with 5 or more years of sexual experience. The more urban the geographic residence of the woman the more likely she was to have acquired HIV-1 infection (p < 0.001). In the urban and peri-urban zones the poorest woman were at significantly higher risk of incident HIV-1 infection than women reporting higher household income. In a multivariate analysis young maternal age marital status (being single divorced or widowed) multiple sexual partners and a history of sexually transmitted diseases remained strongly associated with incident HIV-1 infection. Geographic residence hormonal contraception and receipt of injections were no longer significantly associated with incident HIV-1 infection when these other factors were accounted for simultaneously. Among young Rwandan women the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection. Interventions should focus on young teenagers before they become sexually active. (authors)
TL;DR: These data indicate that HIV infection among homeless adults and runaway youth is an important public health problem and HIV prevention and treatment should be integrated into comprehensive health and medical programs serving homeless populations.
Abstract: ObjectivesHomeless persons have an increased risk of HIV infection because of a high prevalence of HlV-related risk behaviors. These include drug use, sexual contact with persons at risk for HIV infection, and the exchange of sex for drugs. The objectives of this investigation were to describe HIV s
TL;DR: In this paper, the enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS.
Abstract: Objective To determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS. Methods sCD30 values were determined by an enzyme-linked immunosorbent assay (ELISA) on serum samples collected at the time of the first evidence of HIV-1 infection in 110 individuals with a median follow-up of 56 months (range, 12–88 months), at the A1 (74 cases) or A2 (36 cases) stages of the 1993 revised Centers for Disease Control and Prevention classification. The data were evaluated using established clinical and immunological parameters, including circulating CD4+ T-cell count. The controls were 110 blood donors and 51 HIV-1 -negative subjects belonging to groups at risk for HIV-1 infection. Results Elevated sCD30 levels ( 20 U/ml) were found in 83.6% of HIV-1 -infected cases and in 47% of at-risk seronegatives. Data analysis revealed that HIV-1-infected patients with higher sCD30 levels (>35 U/ml) experienced faster disease progression (P = 0.0002). This was also the case in patients at the earliest stage (A1) of HIV infection (P = 0.0027). In these latter cases the predictive value of sCD30 was independent of the initial absolute number of circulating CD4+lymphocytes. Conclusions Serum levels of sCD30 are increased in the large majority of patients in the early phase of HIV-1 infection and represent an indicator of progression to AIDS independent of other prognostic parameters.
TL;DR: A substantial problem of clinical fluconazole failure has developed among HIV-positive patients who have recurrent problematic mucosal candidosis, and the efficacy of alternative treatments is assessed.
Abstract: Objectives To report the occurrence of HIV-related mucosal candidosis that fails to respond to fluconazole, to establish the correlation between in vitro susceptibility testing and clinical failure, and to assess the efficacy of alternative treatments. Design Chart review of all patients with fluconazole failure and all patients with CD4 counts Setting A regional treatment centre for HIV-infected individuals in north-west England. Patients A cohort of 155 HIV-positive individuals with CD4 counts Main outcome measures Clinical fluconazole failure was defined as symptomatic oropharyngeal or oesophageal candidosis despite fluconazole ≥ 100 mg per day for 10 days. In vitro susceptibility to fluconazole was determined for Candida isolates. Cumulative 12-month fluconazole dose and time from first fluconazole therapy and prophylaxis were recorded. Results Nine (5.8%) patients meeting the definition of fluconazole failure were identified. In vitro susceptibility to fluconazole of temporally related oropharyngeal isolates was reduced in all cases. Intravenous amphotericin B was the only effective treatment for these patients when symptoms were severe suggesting azole cross-resistance. One patient, who had received alternative treatments for 9 months, reverted from in vitro and clinical fluconazole sensitivity but relapsed within 6 weeks of resuming fluconazole. The median fluconazole dose over the preceding 12 months for the eight adult cases was 386 mg weekly. The median dose for the same period was 79 mg weekly in 28 patients with CD4 counts Conclusion A substantial problem of clinical fluconazole failure has developed among HIV-positive patients who have recurrent problematic mucosal candidosis.
TL;DR: The people most at risk of HIV-1 infection in this rural Ugandan population are young married women who had, presumably, commenced sexual activity recently.
Abstract: OBJECTIVE: To determine sociodemographic risk factors associated with HIV-1 infection in a rural Ugandan population. DESIGN: A population-based survey. METHODS: All adult residents (aged > or = 13 years) in a cluster of 15 neighbouring villages of the Masaka District of south-west Uganda were invited to participate in a sociodemographic and serological survey. Questions relating to sexual behaviour were asked separately in an accompanying case-control study. Socioeconomic data and an unambiguous HIV-1 serostatus were obtained by house-to-house survey for 3809 (72%) of the adult population. The association between serostatus and the following variables were analysed: age, sex, marital status, tribe, religion, education, occupational group, place and frequency of travel and recent history of sexually transmitted disease. RESULTS: Women aged 13-21 years were at a much higher risk than men of the same age [odds ratio (OR), 8.6; 95% confidence interval (CI), 3.0-24.5]. Married people aged or = 25 years, women were at a lower risk than men (OR, 0.72; 95% CI, 0.52-0.98) as were those who were currently married compared with those who were not (OR, 0.47; 95% CI, 0.34-0.64). In both age groups those with a history of a recent genital ulcer were approximately three times more likely to be infected. Muslims had lower risks than non-Muslims (OR, 0.58 for both age groups). CONCLUSIONS: The people most at risk of HIV-1 infection in this rural Ugandan population are young married women who had, presumably, commenced sexual activity recently.
TL;DR: The inability to productively infect macaques previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated response may confer long-term protection against infection, and that AIDS vaccines should be designed to optimize the cellular arm of the immune response.
Abstract: ObjectivesTo analyze correlates of protection in macaques exposed to SIV.MethodsPeripheral blood mononuclear cells (PBMC) from macaques inoculated intrarectally with various dilutions of SIV were examined for their in vitro proliferative response to SIV envelope peptides and generation of SIV-specif
TL;DR: The SLK cell line is of endothelial cell origin and the first human cell line to induce KS-like tumors in recipient animals, and the expression of urokinase and its receptor suggests a paracrine and autocrine interaction that may be important for the growth of the tumor.
Abstract: ObjectiveTo characterize a Kaposi's sarcoma (KS) cell line established from a tumor biopsy from the oral mucosa of an iatrogenically immunosuppressed HIV-negative man.MethodsCells were placed in culture and evaluated by a variety of biologic, serologic, karyotypic, and immunologic procedures. Electr
TL;DR: The AIDS-associated lymphomas represent a heterogeneous set of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages, and Burkitt's-like lymphomas, which fulfill at least the key criteria for antigen competence.
Abstract: The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)