A sudden epidemic of HIV type 1 among injecting drug users in the former Soviet Union: identification of subtype A, subtype B, and novel gagA/envB recombinants

OBJECTIVES: The choice of cisatracurium, especially for patients with organ dysfunction, seems to be beneficial, because of organ-independent Hofmann-elimination and less histamine release propensity. This study was designed to investigate pharmacodynamics and intubating conditions after bolus administration of 0.15 mg/kg cisatracurium (3 x ED95) in patients with renal failure and maintained with isoflurane/N2O in oxygen. METHODS: 20 patients with renal failure and 19 patients with normal renal function were studied. Anaesthesia was induced with fentanyl (2-3 micrograms/kg) and thiophentone (4-7 mg/kg). After rapid bolus administration of 0.15 mg/kg cisatracurium (3 x ED95), onset time and intubating conditions were assessed. Clinical duration (DUR 25%), recovery index and duration 90% were investigated by acceleromyography. Changes of mean arterial blood pressure and/or heart rate > or = 20% were defined as clinically significant. RESULTS: The onset time (3.1 +/- 0.8 min) was shorter in patients without renal failure (Cis-1) than in patients with normal renal function (3.6 +/- 0.8 min), but without statistical significance. Intubating conditions, scored according to a 3-step scale, were slightly better in patients with normal renal function. Other pharmacodynamic parameters did not differ significantly. However, a small tendency to a prolonged recovery with a wide inter-individual variety was characteristic for patients with renal failure. Regarding the hemodynamic actions, only minor individual cardiovascular changes occured. No clinical evidence of histamine release was observed in any patient. CONCLUSIONS: The result of this clinical study suggest, that cisatracurium is a suitable choice for patients with renal failure. The necessity for an intraoperative neuromuscular monitoring is given by the marked heterogeneity in the recovery parameters in patients with renal failure.     

Molecular epidemiology of an HIV-1 subtype A subcluster among injection drug users in the Southern Ukraine

Phylogenetic characterization of primary isolates from 17 HIV-1-infected individuals within a recent epidemic in the city of Odessa, Ukraine was conducted. The isolates were drawn from two time periods, 1993 and 1996. The 1996 isolates coincided with the first apparent expansion of HIV-1 among injection drug users (IDU). Multi-locus phylogenetic analysis indicated that HIV-1 gag, env, tat, and long terminal repeat (LTR) sequences all conformed to the HIV-1 classification of a subcluster within subtype A. There was no evidence for intersubtype recombinants among these isolates. A number of potential signature sequences, particularly within env, were identified in these two time periods, possibly suggesting a selective pressure on viral evolution among IDU. Results of this study are consistent with a recent introduction and subsequent independent evolution of an HIV-1 subtype A subcluster among IDU in the Southern Ukraine. This study demonstrates a congruence of multi-locus phylogenetic analysis, and suggests that non-B genetic subtypes, such as HIV-1 subtype A, may become relevant to the study of IDU transmission in the future.     

Lower prevalence and incidence of HIV-1 syncytium-inducing phenotype among injecting drug users compared with homosexual men

OBJECTIVE: To study the prevalence, incidence and predictive value for progression to AIDS of the HIV-1 syncytium-inducing (SI) phenotype in HIV-infected injecting drug users (IDU) compared with HIV-infected homosexual men. DESIGN: Two prospective cohort studies on HIV-1 infection among IDU and homosexual men. METHODS: HIV-infected IDU (n = 225) and homosexual men (n = 366) without AIDS were studied from March 1989 through December 1993. Data on laboratory markers, including the presence of SI variants, demographics, behavioural characteristics and clinical events were collected at every visit. RESULTS: At baseline, SI variants were detected in 4% of IDU and 17% of homosexual men. During the study period 18 IDU and 68 homosexual men switched from non-SI to SI phenotype (4-year cumulative incidence, 14.6 and 28.4%, respectively) before AIDS diagnosis. Among participants with a documented date of HIV infection the cumulative incidence of SI was lower among IDU than homosexual men (4-year cumulative incidence, 6.2 and 20.7%, respectively). At AIDS diagnosis, 21% of all AIDS cases among IDU had the SI phenotype compared with 54% among homosexual men. In both risk groups an accelerated CD4 decline was found after the non-SI-to-SI switch. The SI phenotype appeared to be a predictor of AIDS (multivariate relative hazard, 5.33), independent of CD4 cell count and p24 antigen at baseline. In the multivariate time-dependent analysis, the relative hazard of SI phenotype decreased considerably, which is consistent with the hypothesis that the effect of SI phenotype on progression to AIDS is mediated by CD4 cell count. CONCLUSION: The SI phenotype is associated with accelerated CD4 decline and progression to AIDS in both risk groups. The remarkable lower prevalence and incidence of the SI phenotype among IDU may implicate a difference in pathogenesis and natural history of HIV infection linked to transmission group.     

HIV/AIDS-related behavior change among injecting drug users in different national settings

1. The ability of airway epithelial cells to produce insulin-like growth factor I may be important in the pathogenesis of subepithelial fibrosis observed in the airways of patients with asthma. We determined whether human airway epithelial cells are capable of producing polypeptide mediators that could induce fibroblast proliferative activity, in particular insulin-like growth factor I. 2. We examined 12 primary cultures of human airway epithelial cells grown to confluence on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and subsequent release of Methylene Blue, increased proliferation of human fetal lung fibroblasts was detected in conditioned media from airway epithelial cells. The median stimulation of fibroblast proliferation was 49.9% (range 25.6-113.3%) above control values (observed at 1:2 dilution of media). 3. A neutralizing antiserum to insulin-like growth factor I partly inhibited fibroblast proliferation induced by epithelial cell conditioned media by 52.2% (49.9-109%; n = 5). 4. Radioimmunoassay for insulin-like growth factor I in conditioned media demonstrated a median concentration of 54.1 ng/ml (32.4-96.8 ng/ml). 5. Insulin-like growth factor I mRNA was detected in epithelial cell monolayers by Northern blot analysis using an insulin-like growth factor I cDNA probe. 6. The insulin-like growth factor I gene is expressed in cultured human airway epithelial cells, which also secrete insulin-like growth factor I protein. Insulin-like growth factor I also accounts for the major mitogenic activity for fibroblasts of cultured human epithelial cell conditioned media. Insulin-like growth factor I may function in a paracrine manner to modulate fibroblast behaviour and may be involved in airway processes, such as those occurring in asthma.     

Declining seroprevalence in a very large HIV epidemic: injecting drug users in New York City, 1991 to 1996

OBJECTIVES: This study assessed recent trends in HIV seroprevalence among injecting drug users in New York City. METHODS: We analyzed temporal trends in HIV seroprevalence from 1991 through 1996 in 5 studies of injecting drug users recruited from a detoxification program, a methadone maintenance program, research storefronts in the Lower East Side and Harlem areas, and a citywide network of sexually transmitted disease clinics. A total of 11,334 serum samples were tested. RESULTS: From 1991 through 1996, HIV seroprevalence declined substantially among subjects in all 5 studies: from 53% to 36% in the detoxification program, from 45% to 29% in the methadone program, from 44% to 22% at the Lower East Side storefront, from 48% to 21% at the Harlem storefront, and from 30% to 21% in the sexually transmitted disease clinics (all P < .002 by chi 2 tests for trend). CONCLUSIONS: The reductions in HIV seroprevalence seen among injecting drug users in New York City from 1991 through 1996 indicate a new phase in this large HIV epidemic. Potential explanatory factors include the loss of HIV-seropositive individuals through disability and death and lower rates of risk behavior leading to low HIV incidence.     

Infection of baboons with a simian immunodeficiency virus/HIV-1 chimeric virus constructed with an HIV-1 Thai subtype E envelope

OBJECTIVE: To construct an infectious chimeric simian immunodeficiency virus/HIV-1 (SHIV) with the envelope of a Thai subtype E HIV-1 strain for use in a non-human primate model. METHODS: A novel SHIV genome was derived using the sequences of the ectodomain of the envelope gene from the Thai subtype E strain, HIV-1(9466). This SHIV (SHIV9466.33) was recovered by cocultivation from human peripheral blood mononuclear cells (PBMC) after transfection of human rhabdosarcoma cells. Rhesus macaque and baboon PBMC were screened in vitro for susceptibility to infection with SHIV9466.33. After successful infection of baboon PBMC, four animals were inoculated intravenously with SHIV9466.33 and monitored for plasma viral RNA, virus isolation from the PBMC, seroconversion, T-cell subsets, and signs of disease. RESULTS: SHIV9466.33 was able to infect PBMC from 12 out of 14 baboons. All four of the baboons selected for in vivo inoculation became infected. Peak plasma viral RNA levels of 8000 to 700,000 RNA copies/ml were measured at 2 weeks post-inoculation. Virus was isolated from the PBMC of all four baboons during acute infection, and all seroconverted. Although transient declines in CD4+ T-cells were observed during early infection, CD4+ levels remained within normal ranges thereafter. In contrast, in vitro cultures of PBMC of four rhesus macaques were not susceptible to infection with SHIV9466.33. CONCLUSION: SHIV9466.33 containing an HIV-1 subtype E envelope displayed tropism for baboon PBMC but not for rhesus macaque PBMC. This chimeric virus established infection and induced antiviral antibodies in baboons inoculated by the intravenous route with cell-free virus. Thus, infection of baboons with SHIV9466.33 will serve as an important animal model for future studies of HIV-1 vaccine efficacy.     

Phenotypic and genetic analysis of a variant of human immunodeficiency virus (HIV-1) subtype B, isolated in Russia]

Oral malignant neoplasms are very common in old dogs. The prognosis of oral malignant melanoma (MM) for long-term survival is poor, because of early metastasis and delayed diagnosis. Oral MM in immature dogs is rare. A case of oral MM in an immature dog is described. The diagnostic workup includes radiographs of the tumor and thorax, a cytologic examination of the regional lymph nodes and a biopsy of the tumor. The therapy with the best chance of success is the radical surgical excision of the tumor.     

The incubation period to AIDS in injecting drug users estimated from prevalent cohort data, accounting for death prior to an AIDS diagnosis

OBJECTIVE: To estimate the incubation-period distribution (time from seroconversion to AIDS) accounting for death before an AIDS diagnosis (DBAD) in a cohort of injecting drug users (IDU) in Amsterdam, The Netherlands and to compare these estimates with those previously obtained from a contemporaneous study of homosexual and bisexual men in Amsterdam carried out using the same facilities. DESIGN: Participants in a cohort study begun in Amsterdam at the end of 1985 have scheduled follow-up visits every 4 months. All participants of Dutch nationality and who had two or more follow-up visits before January 1996 from which CD4 measurements were available were included in this study. Data concerning AIDS diagnosis and death were verified through review of national and municipal registries. METHODS: Because time of seroconversion was unknown for study participants and because IDU are at substantial risk for DBAD, we used a Markov model with CD4-based stages that allows for DBAD. The parameters in this model were estimated using the method of maximum likelihood and confidence intervals were calculated using bootstrap methods. RESULTS: A total of 173 IDU (134 seroprevalent, 39 seroincident) made 1829 visits. Nearly 10% of the visits were non-consecutive. Forty-five IDU developed AIDS and 25 died without an AIDS diagnosis. We estimated that 24% [95% confidence interval (CI), 17-25%] of IDU die before an AIDS diagnosis. As a result, the median time from seroconversion to AIDS (10.5 years; 95% CI, 9.1-10.7 years) is considerably longer than the median time from seroconversion to death (8.3 years; 95% CI, 7.9-8.5 years). Conditional on survival to an AIDS diagnosis, the median time to AIDS is 8.2 years (95% CI, 7.7-8.7 years). The median survival time after a diagnosis of AIDS is estimated to be 1.0 years. CONCLUSION: The high occurrence of DBAD in IDU has a considerable influence on estimates of the incubation-period distribution. Progression from seroconversion to death was faster in the IDU cohort than in a cohort of homosexual men in Amsterdam (median, 8.3 years and 9.6 years, respectively). However, progression to AIDS conditional on survival to an AIDS diagnosis seems to be similar in both the IDU cohort and in the cohort of homosexual men (median, 8.2 years and 8.3 years, respectively).     

A qualitative investigation into an HIV outbreak among injection drug users in Vancouver, British Columbia

The effect of Cd, Cu, Zn, Hg, and Pb solutions at various concentrations, on the restoration potential of the leaves of Portulaca oleracea was tested. All the trace metals completely affected the shoot regeneration. The degree of their effect on root regeneration, however, varied. Early initiation of parental leaf decay was also observed. The order of their relative effect on the regeneration process was: Cd > Cu > Zn > Hg > Pb.     

Production of HIV-1 by human B cells infected in vitro: characterization of an EBV genome-negative B cell line chronically synthetizing a low level of HIV-1 after infection

Human immunodeficiency virus type 1 (HIV-1) has tropism for helper T lymphocytes and cells of the monocyte/ macrophage lineages. HIV-1 can also infect other cell types, including B cells. We show here that 10% of fresh circulating B cells from HIV-1-seronegative donors (i) express the CD4 receptor and CCR5 and CXCR4, two recently described coreceptors for HIV-1 and (ii) are permissive to HIV-1 with de novo proviral DNA integration following ex vivo infection by either SI (syncytium-inducing) or NSI (non-syncytium-inducing) isolates. To get further information on the interaction between HIV and B cells, the susceptibility of several EBV-positive or -negative B cell lines to infection by SI and NSI isolates was checked. Following infection of an EBV- CD4+ CXCR4+ CCR5- B cell line (DG75) by an SI HIV-1 isolate, we obtained a cell line which chronically produced low-level infectious HIV-1 for 2 years (HIV-DG75). Immunocytochemical data, combined with in situ PCR data, established that HIV-DG75 cells consist of at least three populations uninfected cells, infected virus-producing cells, and infected but nonproducing cells. Moreover, HIV-DG75 cells which express p24 antigen do not go into apoptosis, contrary to T lymphocytes. We infer from these results that B cells could constitute a reservoir of infectious virus in infected patients.     

Comparison of NucliSens and Amplicor monitor assays for quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma of persons with HIV-1 subtype A infection in Abidjan, C?te d'Ivoire

We compared the sensitivity and accuracy of the NucliSens assay and those of both the standard and modified (addition of a new primer set, primer mix 1, supplied by Roche) Amplicor HIV Monitor assays to quantify human immunodeficiency virus type 1 (HIV-1) RNA in persons infected with HIV-1 subtype A in Abidjan, C?te d'Ivoire. Seventy-one plasma samples from HIV-1-seropositive persons at different stages of HIV infection and 15 samples from HIV antibody-negative persons were analyzed. The HIV-1 genetic subtype was determined either by DNA sequencing or by a restriction fragment length polymorphism assay. Of the 71 samples, 70 (98%) were subtype A and 1 was subtype G. Of the 70 subtype A samples, the proportion of RNA-positive plasma samples and mean HIV-1 RNA levels were significantly higher by the modified HIV Monitor assay (n = 67 [96%]; mean RNA levels, 5.2 log10 HIV-1 RNA copies/ml) than the NucliSens assay (n = 56 [80%]; 4.3 log10 HIV-1 RNA copies/ml) or the standard HIV Monitor assay (n = 44 [63%]; mean RNA levels, 3.8 log10 HIV-1 RNA copies/ml) (all P values were <0.05). The HIV-1 RNA levels by the modified HIV Monitor assay correlated significantly with those by the NucliSens assay (r = 0.76; P < 0.001) and the standard HIV Monitor assay (r = 0.57; P < 0.001), as did the RNA levels by the NucliSens and the standard HIV Monitor assays (r = 0.60; P < 0. 001). Lower CD4 cell counts were significantly correlated with higher HIV-1 RNA levels by all three assays (r = -0.47 for the NucliSens assay, -0.45 for the standard HIV Monitor assay, and -0.62 for the modified HIV Monitor assay). These results indicate that the modified HIV Monitor assay has the highest sensitivity and efficiency at quantifying the levels of RNA in persons infected with HIV-1 subtype A and thus constitutes a valuable tool for the monitoring of RNA levels in areas of Africa were HIV-1 subtype A is predominant.     

Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar. This confirms a previous conclusion about the prevalence of A/C serotype among intravenous narcomaniacs in the former USSR.