Showing papers in "AIDS in 1992"

HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay.

Abstract: ObjectiveWe have previously demonstrated that detection of syncytium-inducing (SI) HIV-1 in asymptomatic seropositive individuals is associated with rapid progression to AIDS. In the present study, we sought to develop and evaluate an HIV-1 phenotyping assay for the screening of large numbers of ind

Specific Nutrient Abnormalities in Asymptomatic HIV-1 Infection

Abstract: ObjectiveTo determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection.DesignA longitudinal investigation to determine biological, psychological and social factors th

The epidemiology of HIV-1 infection in urban areas, roadside settlements and rural villages in Mwanza Region, Tanzania.

Abstract: OBJECTIVE: To determine the prevalence of HIV-1 infection and to identify the most important risk factors for infection. DESIGN: A cross-sectional population survey carried out in 1990 and 1991 in Mwanza Region, Tanzania. METHODS: Adults aged 15-54 years were selected from the region (population, 2 million) by stratified random cluster sampling: 2434 from 20 rural villages, 1157 from 20 roadside settlements and 1554 from 20 urban wards. Risk factor information was obtained from interviews. All sera were tested for HIV-1 antibodies using enzyme-linked immunosorbent assay (ELISA); sera non-negative on ELISA were also tested by Western blot. RESULTS: The response rate was 81%. HIV-1 infection was 1.5 times more common in women than in men; 2.5% of the adult population in rural villages, 7.3% in roadside settlements and 11.8% in town were infected. HIV-1 infection occurred mostly in women aged 15-34 years and men aged 25-44 years. It was associated with being separated or widowed, multiple sex partners, presence of syphilis antibodies, history of genital discharge or genital ulcer, travel to Mwanza town, and receiving injections during the previous 12 months, but not with male circumcision. CONCLUSION: This study confirms that HIV-1 infection in this region in East Africa is more common in women than in men. The results are consistent with the spread of HIV-1 infection along the main roads. There is no evidence that lack of circumcision is a risk factor in this population.

HIV risk factors in three geographic strata of rural Rakai District, Uganda

Abstract: Objectives: To examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci tor local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. Design and methods: Serological, sociodemographic, knowledge/behaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. Results: Fifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. Conclusion: Sexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.

International epidemiology of HIV and AIDS among injecting drug users.

Abstract: HIV/AIDS and iv drug use (IVDU) are of significant multinational scope and growing. Supporting increased IVDU in many countries are countries geographical proximity to illicit drug trafficking distribution routes law enforcement efforts which increase the demand for more efficient drug distribution and consumption and countries infrastructural and social modernization. Given the failures of intensified law enforcement efforts to thwart the use and proliferation of illegal drugs countries with substantial IVDU should look away from preventing use to preventing HIV transmission within drug user populations. With HIV seroprevalence rates rapidly reaching 40-50% in some developing country IVDU groups a variety of prevention programs is warranted. Such programs should be supported and implemented while prevention remains feasible. This paper examines the variation in HIV seroprevalence among IVD users rapid HIV spread among users HIV among IVDUs in Bangkok emerging issues in HIV transmission among IVDUs non-AIDS manifestations of HIV infection among IVDUs prevention programs and effectiveness and harm reduction.

Expression of activation antigens, HLA-DR and CD38, on CD8 lymphocytes during HIV-1 infection.

Abstract: Objective To study the expression of the activation markers human leukocyte antigen (HLA)-DR and CD38 antigen on CD8+ T-lymphocytes in HIV-infected subjects and HIV-negative controls. Design Two- and three-colour flow-cytometric analysis. Methods Fresh peripheral venous blood was obtained from 16 HIV-infected subjects, representing four different stages of HIV disease, and from six HIV-negative controls. Three-colour lymphocyte immunophenotyping was performed using peridinyl chlorophyll-A protein (PerCP)-conjugated anti-CD8 monoclonal antibody (MAb) in combination with anti-HLA-DR (phycoerythrin) and anti-CD38 (fluorescein isothiocyanate) MAb. Results The relative percentage of the lymphocyte populations thus defined differed between HIV-negative and HIV-positive subjects and between HIV-infected subjects at different clinical stages of disease. Simultaneous expression of HLA-DR and CD38 within the CD8 T-lymphocyte compartment increased from 8% in controls to 49% in asymptomatic HIV-infected subjects (P less than 0.005). Symptomatic patients differed from asymptomatic seropositives by a further increase in the HLA-DR+ CD38+ CD8 subset. In AIDS patients, the HLA-DR+ CD38- CD8 subset decreased (P less than 0.05) and the HLA-DR- CD38+ CD8 subset increased (P less than 0.05), compared with the other HIV disease stage patients. Conclusion There is a stage-associated pattern of HLA-DR and CD38 expression on CD8 T-lymphocytes during HIV infection; specific phenotypic patterns may have functional correlates in the host response to the virus.

Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral N-acetylcysteine.

Abstract: Objective.To determine whether a single oral dose of N-acetylcysteine corrects the deficiency of cysteine and glutathione in plasma and mononuclear cells of HIV-infected patients.Design.Pharmacokinetic and pharmacodynamic study.Methods.Cysteine and glutathione were measured in plasma and peripheral

Zidovudine-induced restoration of cell-mediated immunity to mycobacteria in immunodeficient HIV-infected patients.

Abstract: Objective: To describe a localized form of Mycobacterium avium intracellulare (MAI) infection occurring concurrently with the restoration of cutaneous delayed-type hypersensitivity (DTH) responses to mycobacterial antigens after commencement of ziclovudine therapy in immunodeficient HIV-infected patients. Patients: The first 108 Western Australian patients with a CD4+ T-cell count of <200 $$ 106/1 and/or symptomatic disease to be given zidovudine (ZDV), of whom 72 had adequate DTH data. Methods: DTH responses to seven antigens were measured by the 'Multitest' method before and on at least two occasions during the 6 months after commencing ZDV. All patients were reviewed at regular intervals and clinical events recorded. Results: Of the 64 patients who were anergic to tuberculin before commencing ZDV, 27 (42%) developed a DTH response to tuberculin after ZDV. Four of the nine patients with a 'Multitest' tuberculin response of >=8mm and one patient who developed a positive Mantoux test to M. avium purified protein derivative developed an illness characterized by localized MAI infection, lymphadenopathy and/or severe fevers after 1-2 weeks. Conclusion: The development of localized MAI infection and/or fevers shortly after commencing ZDV in immunodeficient HIV-infected patients may reflect restoration of cellular immunity to mycobacterial antigens in some patients rather than early failure of therapy or hypersensitivity to ZDV.

Situational factors and thought processes associated with unprotected intercourse in young gay men.

Abstract: This study investigated the types of justifications if any that young gay men give themselves at the time they make the decision to have unprotected anal intercourse and the types of occasions on which they are most at risk of having unprotected intercourse. In structured interviews gay men ages 15-21 were asked to recall 2 sexual encounters from the preceding 6 months; 1 in which they had unprotected anal intercourse ("unsafe" encounter) and 1 in which they had resisted a strong temptation to have unprotected intercourse ("safe" encounter). The authors studied both types of encounters to enable them to identify those situational variables which were distinguishable between them. The 1st 2 factors which emerged from a Factor Analysis of the self-justification data ("unsafe" encounter n=219) involved respectively high-risk behavior in response to a negative mood state and inferring from perceptible characteristics that the partner was unlikely to be infected. The most commonly reported self-justification was of this latter type. In respondents recalling both encounters (n=115) sexual desires mood communication and use of "dirty talk" distinguished between the encounters. In contrast type of partner consumption of alcohol or drugs desire for excitement and use of pornography did not. Results are discussed in relation to those obtained in their earlier study of older gay men. Young gay men appear to be more single-minded about what they want to do sexually and more likely to infer from perceptible characteristics that their partner is unlikely to be infected. In young gay men a negative mood state is associated with unsafe sex an opposite finding to that obtained with older gay men. The results also suggest the possible importance of failure to communicate about desires concerning safe sex and the use of "dirty talk"; these may help to facilitate the occurrence of unsafe sex. (authors)

Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines.

Abstract: Objective: To study expression of HIV-1 in human glial cell lines. Design: Chronically HIV-1-infected glial cell lines were established to evade potential artefacts resulting from unphysiological viral entry (i.e., transfection). These cell lines were used to study viral expression and regulation. Methods: Chronically infected glial cell lines were established by terminal dilution cloning of human glioma cells exposed to HIV-1. Virus production and expression were assayed by measuring reverse transcriptase activity, p24-antigen levels and syncytia-inducing capacity in C8166 target cells (extracellular), or by indirect immunoperoxidase staining, immunoblot analysis, and p24- and Nef-antigen-capture enzyme-linked immunosorbent assays (intracellular). HIV-long terminal repeat (LTR)-dependent expression of the chloramphenicol acetyltransferase reporter gene was determined in transient transfection assays. Results: Culture supernatant from chronically HIV-1-infected glial cells contained only low levels of virus compared with chronically HIV-infected fibroblasts and T-lymphoma cells. Detailed study of HIV-antigen expression in representative glial cell line TH4-7-5 indicated the presence of all major structural proteins, albeit at low levels, and of Vif, Tat, Rev and Nef. Intracellular levels of Nef exceeded p24-antigen levels by approximately 10-fold. Virus was recovered from TH4-7-5 cells by cocultivation with blood-derived target cells, indicating that low-level virus production is not due to defective provirus. Prominent negative regulatory element (NRE)-mediated suppression of exogenous HIV-LTR activity was observed in TH4-7-5 cells and was unequalled by chronically HIV-producing fibroblast cells or by uninfected fibroblast and glial cells. Conclusions: Our results suggest that restricted virus production by chronically infected glial cells involves LTR-mediated regulation of virus expression.

Treatment of intestinal microsporidiosis with albendazole in patients with AIDS.

Abstract: Objective To determine the clinical and parastilogical repsonse to treatment of intestinal microsporidiosis with albendazole. Design Open prospective study. Setting Hospital-based HIV/genito-urinary medicine unit. Patients, participants Six consecutive AIDS patients with small intestianl microsporidiosis as the only identified cause of diarrhoea after intensive gastrointestinal investigations. Results Diarrhoea resolved completely in all patients within 1 week of starting treatment, and body weight stabilized or increased. Four patients who relapsed at 19–31 days after the cessation of treatment responded to a second course of albendazole. Degenerative changes occurred in the parasites after treatment, which had not been seen either in pre-treatment biopsies or, in four patients, following therapy with other drugs. Conclusions Albenazole is a useful palliative treatment for microsporidial diarrhoea.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

Abstract: OBJECTIVE This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Seroprevalence of HIV infection in rural South Africa.

Abstract: As part of a population-based malaria surveillance program in late 1990 surveillance agents took blood samples from 979 people who had had a fever within the last 2 weeks and from 4044 healthy people during regular house-to-house visits in rural northern Natal/KwaZulu South Africa to determine HIV seroprevalence and risk factors of HIV infection. 60 (1.2%) people were HIV-1 seropositive. No one had HIV-2 infection. Febrile people had a 30% higher sex-adjusted relative risk (RR) of HIV-1 infection than healthy individuals but this increase was insignificant. Women were at greater risk of HIV-1 infection than men (1.6% vs. 0.4%; age-adjusted RR = 3.8). In fact this risk still existed when the researchers controlled for fever (RR = 3.75) and migrancy (RR = 3.2). The fall in the RR for women from 3.8 to 3.2 when controlled for migrancy suggested an underrepresentation of migrant male workers in the study sample. 2.3% of the women in their childbearing years (15-44) were HIV-1 seropositive indicating an increased likelihood of transmission of HIV-1 to newborns. The youngest person afflicted with HIV-1 was a 12-year-old female and the oldest was a 66-year-old woman. No 10-to-19-year-old males tested HIV-1 positive while 1.7% of the 10-to-19-year-old females did suggesting that the young females had sex with older men. This may have indicated teenage prostitution and sexual abuse. 2.9% of the people who changed their place of residence within the last year (migrancy) had HIV-1 infection. For women it was linked to a 2.4 times higher RR (age-adjusted) of HIV-1 infection. For men the age-adjusted RR was even greater (7.3). Even though HIV-1 seroprevalence was about 45% greater in areas crossed by the main national road than it was in other areas (1.3% vs. 0.9%) the difference was not significant. Since migrants were a key source of HIV-1 infection improvement in social conditions allowing families to live together and to settle in their communities may reduce HIV-1 transmission.

Isolation and characterization of a new chimpanzee lentivirus (simian immunodeficiency virus isolate cpz-ant) from a wild-captured chimpanzee.

Abstract: ConclusionsThis study shows that natural infection of wild-captured chimpanzees with an HIV-related virus may not be uncommon. The diversity of the two chimpanzee isolates, the different geographical origin and the absence of disease suggest that chimpanzees have not recently become SIVcpz-infected.

Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection.

Abstract: Objective: To establish the incidence of herpes simplex virus (HSV) ulceration in relation to CD4+ cell counts in HIV-infected patients.Design: Swabs were taken from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+ cell counts were performed at regular intervals.Setting: The HIV unit at a London teaching hospital (the Royal Free Hospital, London, UK).Patients: All HIV-infected patients (n = 500) attending the HIV unit.Results: Two hundred and twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62 (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4 + cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of 127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of patients with CD4 + cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive cultures compared with 25 of 71 (35.2%) of patients with higher counts (P < 0.0001). This trend was observed with swabs from all body sites; sufficient samples were available from oral and perianal lesions to demonstrate statistical significance (P < 0.0001 and P = 0.007, respectively).Conclusions: These results show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l and thus provide important data for the design of studies of anti-HSV prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on presentation.

Identification and quantitation of HIV-1 in the liver of patients with AIDS.

Abstract: Objective To detect and quantify HIV-1 in the liver in vivo. Design Fourteen liver biopsy samples and corresponding blood lymphocytes and monocytes from patients with AIDS were studied for HIV-1 using quantitative polymerase chain reaction (PCR). In addition, expression of HIV-1 antigen and messenger (m) RNA in 10 autopsy liver specimens was examined by immunohistochemistry and in situ hybridization. Results The amount of HIV-1 DNA in nine liver samples ranged from 850 to 27,000 copies per 10(6) cells, with mean and median values of 8150 and 3500 copies per 10(6) cells, respectively. Five other samples had no detectable HIV-1 DNA by PCR. Intracellular expression of HIV-1 antigen and mRNA was also detected in both Kupffer cells and hepatocytes by in situ studies. Conclusion These findings strongly indicate that HIV-1 could replicate in the liver of a majority of patients with AIDS.

Rapid generation of sequence variation during primary Hiv-1 infection

Abstract: OBJECTIVE HIV-1 undergoes extensive genetic variation in infected individuals. The extent of genetic variation has been examined in patients with AIDS, but little is known regarding the appearance of HIV-1 genetic variation immediately following infection during the primary phase of HIV-1 infection prior to seroconversion. DESIGN We examined HIV-1 genetic variation during this early phase of HIV-1 infection by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 variable region and the CD4-binding domain. RESULTS Our results demonstrate that extensive sequence variation is seen early after infection, although a predominant HIV-1 species is maintained. CONCLUSIONS The type of variants that occur are dynamic, changing over time, and the mutations seen are consistent with those expected from random occurrence, unlike the pattern of variation previously reported during later stages of disease.

Association between HIV infection and cervical neoplasia: implications for clinical care of women at risk for both conditions.

Abstract: Objective Both AIDS and cervical neoplasia (CN) can result from sexual transmission of HIV infection and may affect similar groups of women. Available data on the association between AIDS and CN have practical implications for gynecological care. We review these data to provide an estimate of the magnitude of the association between CN and HIV infection. Design Twenty-one studies were reviewed, including reports and abstracts published from January 1986 to July 1990. Of these, five included a comparison group and had sufficient data for inclusion in the analysis. Results All five controlled studies reported a significant association between HIV infection and CN. One included women with both intraepithelial and invasive lesions; the other four considered women with intraepithelial lesions only. The summary odds ratio indicated that the odds of HIV-infected women having CN are 4.9 (95% confidence interval, 3.0-8.2) times that of HIV-negative women. Conclusions Research is needed to clarify etiological relationships and the role of human papillomavirus in the causal pathway of the observed association. Meanwhile, available data are sufficient to encourage regular Papanicolaou's smear screening of HIV-infected women, and HIV testing and counseling of women with CN considered at risk for HIV infection.

Competition between zidovudine-sensitive and zidovudine-resistant strains of HIV

Abstract: ObjectiveTo investigate competitive interactions between zidovudine-sensitive and resistant strains of HIV within the context of host-parasite population dynamic interactions between CD4 + cells and HIV.DesignA mathematical model of the population dynamics of CD4 + cells, sensitive HIV and resistant

The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study.

Abstract: OBJECTIVE To determine the safety and pharmacokinetics of the nucleoside analogue, 3TC DESIGN A Phase I, open-label, single-centre study METHODS Twenty asymptomatic, HIV-infected male patients with CD4 lymphocyte counts < 500 x 10(6)/l who had not received previous antiretroviral therapy completed the study Each patient received a single intravenous dose followed by a single oral dose of 3TC Four patients were dosed at each of five dose levels (025, 10, 20, 40 and 80 mg/kg) RESULTS The most commonly reported adverse event was headache, which was generally reported to be mild The mean bioavailability of 3TC was 82% following oral administration The majority of the dose (approximately 70%) was excreted unchanged in the urine CONCLUSIONS Overall, 3TC was well tolerated following dosing, and there were no significant changes in the safety parameters measured Phase I/II clinical trials with 3TC are ongoing to evaluate its safety, pharmacokinetics and preliminary activity

Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype.

Abstract: To determine the kinetics of decline of CD4+ lymphocytes in HIV-1-infected asymptomatic homosexual men CD4+ lymphocytes were enumerated in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3-month intervals over 5 years During follow-up, 45 men progressed to AIDS (excluding cases presenting with Kaposi's sarcoma) Correlation between rate of CD4+ cell decline and presence of a particular HIV-1 biological phenotype was analysed in 43 participants CD4+ cell counts declined slowly and continuously in HIV-1-seropositive men who remained asymptomatic during follow-up A biphasic CD4+ cell count decline was observed in the group who developed AIDS: the decline was slow and steady (56 x 10(6)/l per month, similar to that observed in the asymptomatic group) until 18 months before AIDS diagnosis, but became three to five times faster thereafter Rapid CD4+ cell decline was significantly related to syncytium-inducing, fast-replicating HIV-1 isolates; during the period of slow and steady CD4+ cell count decline, non-syncytium-inducing isolates were predominant At an average of 18 months preceding AIDS diagnosis, a three to fivefold increase in the rate of loss of CD4+ lymphocytes occurs, and may be related to the appearance of a more virulent HIV-1 phenotype

Systemic dissemination by a newly recognized intestinal microsporidia species in AIDS.

Abstract: OBJECTIVE Primarily to determine whether an intestinal microsporidian recently identified in AIDS patients disseminates from the bowel to infect other organs. DESIGN Disseminated microsporidiosis has been reported in immunocompromised humans, but never due to Enterocytozoon bieneusi, the most common species in AIDS patients and one that evidently infects only enterocytes. In animals, dissemination follows ingestion of Encephalitozoon cuniculi spores, apparently via macrophages, and pathology occurs in, for example, kidneys and brain. A second, un-named Encephalitozoon-like intestinal microsporidia has been identified in five AIDS patients with chronic diarrhea; because it infects lamina propria macrophages, it was logical to investigate its dissemination. METHODS Light and transmission electron microscopy were used to study urine sediment from four out of five patients with biopsy-documented small intestinal infection due to the second intestinal microsporidian. The gall bladder from one patient and autopsy specimens from an E. bieneusi-infected patient were similarly studied. RESULTS Systemic dissemination was documented by detecting abundant spores, both free and within renal tubular and transitional cells, in the urine of two patients. Many of the lamina propria macrophages in these two patients' intestinal biopsies contained microsporidia, while those of the two negative patients either contained only Mycobacterium avium complex or only occasional parasites. The gall bladder was co-infected with this microspordian and with cytomegalovirus. At autopsy, the patient with documented enteritis due to E. bieneusi 2 years before death had disseminated microsporidiosis, not of E. bieneusi, but apparently of the second intestinal species. The microsporidian had caused severe tubulointerstitial nephritis. Parasites were also observed in non-parenchymal cells of the liver and bronchial epithelium. CONCLUSION A newly described Encephalitozoon-like intestinal microsporidian, which causes chronic diarrhea in AIDS patients, can disseminate and cause renal pathology.

Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis.

Abstract: OBJECTIVE We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. DESIGN The trial was a prospective, randomized, and non-blinded study. SETTING The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. INTERVENTIONS Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. MAIN OUTCOME MEASURES Outcome measures were a complete or partial response, recrudescence and relapse. RESULTS A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). CONCLUSION Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Trimethoprim-sulfamethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients: results of a large prospective randomized treatment trial.

Abstract: Objective To compare the clinical efficacy and safety of trimethoprim-sulfamethoxazole (TMP-SMX) with pentamidine in the therapy of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. Patients, participants TMP-SMX (TMP, 20 mg/kg/day plus SMX, 100 mg/kg/day) was compared with pentamidine (4 mg/kg/day), both administered intravenously for 21 days in a prospective randomized treatment trial of 163 patients diagnosed with PCP between November 1984 and May 1988. Results Ninety-two evaluable patients received TMP-SMX as initial therapy; 68 received pentamidine. Failure to complete therapy was common. Of those receiving TMP-SMX, 39 (42%) required change in therapy because of failure to respond, and an additional 31 (34%) because of drug toxicity. This compared with 27 (40%; P = 0.733) and 17 (25%; P = 0.235), respectively, in the pentamidine-treated group. The overall survival rates were similar in the two groups, 62 out of 92 (67%) initially administered TMP-SMX versus 50 out of 68 (74%) initially administered pentamidine (P = 0.402). The survival rates for patients requiring a change in therapy because of failure to respond was 46% (18 out of 39) for the TMP-SMX group compared with 56% (15 out of 27) for the pentamidine group. When a change in therapy was made because of toxicity, survival rates were 97% (30 out of 31) for those receiving TMP-SMX versus 94% (16 out of 17) for those receiving pentamidine. Conclusion TMP-SMX and pentamidine are of equivalent efficacy as initial therapies for PCP in patients with AIDS.

Comparison of early and late feline immunodeficiency virus encephalopathies.

Abstract: Design The study of the early and late stages of encephalopathy following infection by the feline immunodeficiency virus (FIV) was carried out with laboratory and naturally infected cats. Interventions Animals infected experimentally were injected with three different isolates of the virus, administered either intracerebrally or intravenously, and sacrificed at 7 days, 1 and 6 months (intracerebral injection), and 2, 6 and 12 months (intravenous injection) post-inoculation, respectively. Conclusions General features of encephalopathy were found to be identical, regardless of the method of inoculation or the viral strain used. Moderate gliosis and glial nodules, sometimes associated with perivascular infiltrates and white matter pallor, were observed at 1 month (intracerebral injection) and 2 months (intravenous injection), and remained unchanged until 12 months post-inoculation. The fact that these initial stages are identical for intravenously and intracerebrally inoculated cats suggests that the virus enters the brain very quickly in intravenously infected animals. Encephalopathy in cats naturally infected with FIV only consisted of gliosis, glial nodules, white matter pallor, meningeal perivascular calcification and meningitis. These lesions were more frequent and more severe in the group coinfected with feline leukaemia virus and feline infectious peritonitis virus. Although multinucleated cells were rare, the strong similarities between HIV and simian immunodeficiency virus encephalopathies at comparable stages support the view that FIV infection may represent an interesting model for a physiopathological approach of HIV infection of the central nervous system.

HIV-1 biological phenotype and the development of zidovudine resistance in relation to disease progression in asymptomatic individuals during treatment.

Abstract: OBJECTIVE To determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals. METHODS Twenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction. RESULTS Progression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P < 0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations. CONCLUSIONS Conversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.

Cerebrospinal fluid beta 2-microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment.

Abstract: Objective To determine the relationship between cerebrospinal fluid (CSF) beta 2-microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine Design A prospective study Setting Tertiary referral hospital Patients, participants Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection To enter our study, patients had to have an ADC stage of at least 05 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment) A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study Interventions Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed Main outcome measures Patients were staged according to severity of ADC on clinical criteria Neuropsychological test scores were converted to an impairment score CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments Results There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 00001); treatment with zidovudine significantly reduced these concentrations (P = 0013) CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy Conclusions CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy