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PubMed2005

Amplification and cloning of near full-length HIV-2 genomes.

The genomes of human immunodeficiency virus type 2 (HIV-2), like those of HIV-1, are not only extremely variable but are also highly recombinogenic. Determination of subtypes based on partial genomes cannot predict the subtype classification of other regions of the genome owing to the frequent occurrence of recombinant genomes among subtypes. To fully understand the genetic variation and evolution of HIV-2s, full-length viral genomes need to be obtained for genetic analysis. Full-length HIV-2 genomes can also be used as infectious clones to study viral biological characteristics and as reference sequences for phylogenetic analysis. More important, all genes in the obtained genomes can be cloned into expression vectors to produce proteins that can be used as antigens for diagnostic reagents or as immunogens for vaccine development. The long-range polymerase chain reaction technique has recently become a more preferred method than the lambda phage cloning method to obtain near-full-length HIV-2 genomes.

Cloning, Molecular↗
PubMed1997

Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop.

The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo.

Amino Acid Sequence↗
PubMed2000

Dating the common ancestor of SIVcpz and HIV-1 group M and the origin of HIV-1 subtypes using a new method to uncover clock-like molecular evolution.

Attempts to estimate the time of origin of human immunodeficiency virus (HIV)-1 by using phylogenetic analysis are seriously flawed because of the unequal evolutionary rates among different viral lineages. Here, we report a new method of molecular clock analysis, called Site Stripping for Clock Detection (SSCD), which allows selection of nucleotide sites evolving at an equal rate in different lineages. The method was validated on a dataset of patients all infected with hepatitis C virus in 1977 by the same donor, and it was able to date exactly the known origin of the infection. Using the same method, we calculated that the origin of HIV-1 group M radiation was in the 1930s. In addition, we show that the coalescence time of the simian ancestor of HIV-1 group M and its closest related cpz strains occurred around the end of the XVII century, a date that could be considered the upper limit to the time of simian-to-human transmission of HIV-1 group M. The results show also that SSCD is an easy-to-use method of general applicability in molecular evolution to calibrate clock-like phylogenetic trees.

Animals↗
PubMed2006

Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China.

BACKGROUND: Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1) infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized. METHODS AND FINDINGS: Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%), CRF01_AE (40.5%), and B (6.5%) by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes. CONCLUSIONS: This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis.

Normal immature thymocytes respond to activation by undergoing programmed cell death (apoptosis), a physiological deletion mechanism involved in the selection of the T-cell repertoire. In this article, Jean Claude Ameisen and André Capron suggest that inappropriate induction of a form of programmed T-cell death could account for both qualitative and quantitative helper T-cell defects of HIV-infected patients. A model of AIDS pathogenesis is presented that may explain several features of HIV infection, including evolution of the disease and the development of defects in nonimmunological organs.

AIDS Dementia Complex↗
PubMed1990

The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAM) play a central role in host defense against pulmonary infection. The authors studied the number, viability, and ultrastructure of PAM recovered by bronchoalveolar lavage from normal and HIV-infected subjects, and their ability to phagocytose and kill Staphylococcus aureus. PAM from HIV-infected subjects who did not have pneumonia were present in greater numbers and phagocytosed significantly more opsonized Staphylococcus aureus (32.5% and 27.3% for nonsmokers and smokers, respectively) than did PAM from healthy controls (19.5% and 18.2%). In 15 patients with AIDS and pneumonia (due to Pneumocystis carinii in 13/15), viability of PAM and their phagocytic capacity were significantly reduced; in smokers with AIDS and pneumonia, the PAM yield was also dramatically decreased. Killing of S. aureus was similar by PAM from all patient groups. HIV infection was associated with the electron microscopic finding in PAM of extensively ruffled PAM cell-surfaces and ingestion of lymphocytes. Thus, HIV infection stimulates the phagocytic capacity and produces morphologic changes consistent with the possibility that PAM are activated by this retroviral infection. In patients with AIDS who develop pneumonia, especially in smokers, the number, viability and phagocytic capacity of PAM are significantly decreased; our study could not determine whether this diminished activity reflects evolution of the HIV infection or a secondary effect of the pneumonia.

Adult↗
PubMed2006

[Nocardiosis as the first opportunistic disease in a patient with missed HIV infection. Pathomorphism of presentation, clinical course, and evolution].

It is reported on the ground of the most updated literature evidences an infrequent case of multiple cavitating pulmonary infiltrates and a probable liver abscess caused by a Nocardia asteroides disseminated infection heralding a HIV-related profound immunodeficiency who remained missed and undiagnosed until the emerging of this severe opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed2006

Increased neutralization sensitivity of recently emerged CXCR4-using human immunodeficiency virus type 1 strains compared to coexisting CCR5-using variants from the same patient.

CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-using (R5) variants relatively late in the natural course of infection in 50% of HIV-1 subtype B-infected individuals and subsequently coexist with R5 HIV-1 variants. This relatively late appearance of X4 HIV-1 variants is poorly understood. Here we tested the neutralization sensitivity for soluble CD4 (sCD4) and the broadly neutralizing antibodies IgG1b12, 2F5, 4E10, and 2G12 of multiple coexisting clonal R5 and (R5)X4 (combined term for monotropic X4 and dualtropic R5X4 viruses) HIV-1 variants that were obtained at two time points after the first appearance of X4 variants in five participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Recently emerged (R5)X4 viruses were significantly more sensitive to neutralization by the CD4-binding-site-directed agents sCD4 and IgG1b12 than their coexisting R5 viruses. This difference was less pronounced at the later time point. Early (R5)X4 variants from two out of four patients were also highly sensitive to neutralization by autologous serum (50% inhibition at serum dilutions of >200). Late (R5)X4 viruses from these two patients were neutralized at lower serum dilutions, which suggested escape of X4 variants from humoral immunity. Autologous neutralization of coexisting R5 and (R5)X4 variants was not observed in the other patients. In conclusion, the increased neutralization sensitivity of HIV-1 variants during the transition from CCR5 usage to CXCR4 usage may imply an inhibitory role for humoral immunity in HIV-1 phenotype evolution in some patients, thus potentially contributing to the late emergence of X4 variants.

Antibodies, Monoclonal↗
PubMed2000

Convergence of natural and artificial evolution on an RNA loop-loop interaction: the HIV-1 dimerization initiation site.

Loop-loop interactions among nucleic acids constitute an important form of molecular recognition in a variety of biological systems. In HIV-1, genomic dimerization involves an intermolecular RNA loop-loop interaction at the dimerization initiation site (DIS), a hairpin located in the 5' noncoding region that contains an autocomplementary sequence in the loop. Only two major DIS loop sequence variants are observed among natural viral isolates. To investigate sequence and structural constraints on genomic RNA dimerization as well as loop-loop interactions in general, we randomized several or all of the nucleotides in the DIS loop and selected in vitro for dimerization-competent sequences. Surprisingly, increasing interloop complementarity above a threshold of 6 bp did not enhance dimerization, although the combinations of nucleotides forming the theoretically most stable hexanucleotide duplexes were selected. Noncanonical interactions contributed significantly to the stability and/or specificity of the dimeric complexes as demonstrated by the overwhelming bias for noncanonical base pairs closing the loop and covariations between flanking and central loop nucleotides. Degeneration of the entire loop yielded a complex population of dimerization-competent sequences whose consensus sequence resembles that of wild-type HIV-1. We conclude from these findings that the DIS has evolved to satisfy simultaneous constraints for optimal dimerization affinity and the capacity for homodimerization. Furthermore, the most constrained features of the DIS identified by our experiments could be the basis for the rational design of DIS-targeted antiviral compounds.

Codon, Initiator↗
PubMed1997

A comparison of prevalence rates of genital ulcers among persons attending a sexually transmitted disease clinic in Jamaica.

Two cross-sectional surveys were undertaken, from December 1982 to August 1983 and from November 1990 to January 1991, to estimate the prevalence rates of genital ulcer disease (GUD) in all patients presenting with a new sexually transmitted disease (STD) complaint to the STD clinic at the Comprehensive Health Centre in Kingston, Jamaica. Diagnosis of syphilis and human immunodeficiency virus (HIV) infection was based on results of laboratory tests, but diagnosis of the other STDs was based on clinical features. Data from these two surveys were compared, and reported national annual incidence data for GUD reviewed. In 1982/83 6.8% of 23,050 patients had GUD, men (9.3%) more often than women (4.2%; p < 0.001). In 1990/91 the prevalence rate was 12.8%, with increased rates for both men (18.2%) and women (6.8%; p < 0.001). In patients with GUD, a clinical diagnosis of genital herpes was made, in 1982/83 and 1990/91, respectively, in 16.8% and 7.8% of the patients; syphilis, in 12.9% and 18.8%; chancroid, in 12.4% and 13.3%; viral warts, in 5.7% and 6.3%; lymphogranuloma venereum, in 4.1% and 3.9%; and granuloma inguinale, in 3.6% and 2.3%. In men the rate for syphilis was 19% in 1990/91 and 8% in 1982/83 (p = 0.001); and for genital herpes it was 7% in 1990/91 and 17% in 1982/83 (p = 0.025). These reversals were attributed to intense media coverage of herpes in 1982/83. There was no difference in prevalence rates between the two surveys for these diseases in women, or for lymphogranuloma venereum, granuloma inguinale and genital warts in men and women. A clinical diagnosis could not be made in 44.4% of cases in 1982/83 (particularly in men), and in 47.6% of cases in 1990/91. GUDs facilitate transmission and adversely affect the prognosis of HIV. The increase in their prevalence has implications for the evolution of the local HIV epidemic, and should be addressed effectively by strengthening the STD/HIV control programme.

Chancroid↗
PubMed1997

Correlation between antiretroviral resistance mutations, biological parameters, and clinical evolution in zidovudine-treated patients infected with human immunodeficiency virus type 1.

To evaluate the correlation between zidovudine (ZDV) resistance mutations of human immunodeficiency virus type 1 (HIV-1), biological parameters, and clinical evolution, 111 HIV-1-infected patients treated with ZDV were studied. Specific mutations at codons 70, 215, and 41 in the HIV-1 reverse transcriptase coding region conferring resistance to ZDV were detected using a selective polymerase chain reaction. The appearance of ZDV resistance mutations was significantly correlated with baseline clinical stage, CD4+ cell count, and viral load, but not with duration of ZDV therapy or p24 antigen level. In univariate analysis, results showed a prognostic role of mutations at codons 215 and 41 for clinical progression to the acquired immune deficiency syndrome (AIDS) or death. In multivariate analysis after controlling for viral load, CD4+ cell count, and clinical stage, the presence of the mutation at codon 215 (but not at codon 41) remained an independent predictor of subsequent clinical evolution.

Adult↗
PubMed2002

Paradoxical responses in a cohort of HIV-1-infected patients with mycobacterial disease.

SETTING: Paradoxical worsening or relapse of opportunistic infections has been described after initiation of highly active anti-retroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. DESIGN: Retrospective study of a group of 33 HIV-infected patients with mycobacterial disease analysing the incidence and characteristics of patients with and without paradoxical response after starting HAART and/or mycobacterial treatment. RESULTS: Nine patients in the group had paradoxical response. No significant difference of baseline characteristics was observed in these patients. The decrease in viral load was significantly greater among patients with paradoxical response than in patients without. CONCLUSION: No clinical difference was found in the evolution of HIV-infected patients with mycobacterial disease after the resolution of the episode of paradoxical response.

AIDS-Related Opportunistic Infections↗
PubMed1996

The Edinburgh cohort of HIV-positive injecting drug users at 10 years after infection: a case-control study of the evolution of dementia.

OBJECTIVE: To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. DESIGN: Case-control study. PARTICIPANTS: Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. METHODS: Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. RESULTS: Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. CONCLUSION: In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.

AIDS Dementia Complex↗
PubMedDate not supplied

Lipid profile during pregnancy in HIV-infected women.

PURPOSE: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. METHOD: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (PIs) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. RESULTS: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p < .001), 60.8 mg/dL for total cholesterol (p < .001), 13.7 mg/dL for HDL cholesterol (p < .001), and 17.8 mg/dL for LDL cholesterol (p = .001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on PIs. The effect of PIs on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. CONCLUSION: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV.

Adult↗
PubMed1992

Epidemic model of HIV infection and AIDS in Argentina. Status in 1990 and predictive estimates.

The purpose of this paper was to evaluate the prevalence of HIV infection and AIDS in Argentina, to study the dynamics of the spread of HIV and to predict the future course by means of an epidemic model. The model was constructed using differential equations to describe the interactions between members of the various groups at risk. The functional form of the solutions was used in a back calculation procedure using data from cohort studies which were done in other countries (U.S.A. and France) together with data of AIDS cases reported to the National AIDS Program, to determine the time evolution of HIV-infection in each of the groups at risk defined. Results show that HIV was introduced in Argentina during the early 80's and affected persons of the homosexual/bisexual group in a first stage. In April 1990 it was estimated that there were a total of 34,131 HIV-infected persons. Intravenous drug users (IVDU) represented 39.5%, homosexual/bisexual men 47.6% and heterosexual adults 11%. It is estimated that in December 1992 there will be 107,946 HIV-infected persons where heterosexuals contribute with more than 20% of that value. AIDS cases predicted for the same period are 4130, with 1958 among homosexual/bisexual, 1483 among IVDU, 449 in heterosexual adults, 153 in children under 4 years old and 87 among hemophiliacs or patients with blood coagulation disorders. By the end of 1994 the model predicts more than 200,000 HIV infected persons with an important proportion of heterosexual adults and more than 12,000 AIDS cases. The values of this period must be considered as a future possible scenario if the present spread conditions are preserved. Infection among heterosexual adults is at the present time in a first and exponential phase of spread and dominated by transmission from IVDU group and bisexual men. It is concluded that the future course of AIDS epidemic in Argentina may be particularly influenced by changes in the heterosexual behavior particularly in those with a higher degree of exposure to HIV-infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Differences in laboratory parameters in clinical categories (CDC/93) of HIV infection].

OBJECTIVE: To establish the difference between the evolutive clinical categories (CDC/93) of the HIV infection, on the basis of diverse laboratory parameters. MATERIAL AND METHOD: 332 samples of blood, from 118 patients with HIV infection revised every three months from 1986, were studied. Determinations: haematologic, biochemical and immunologic study. Classification in each review by CDC/93 system. Statistical analysis (R-SIGMA) comparing by ANOVA and NEWMANN-KEULS the averages of the laboratory variables in the clinics categories ("A", "B" and "C"). RESULTS: There are very significant laboratory differences (p < 0.01) between the asymptomatic patients ("A") and the AIDS cases ("C"), with important decrease of hemoglobin, platelets, leukocytes, albumin, CD4+ and CD8+ T cells in the "C" category. On the contrary there is a marked increase of erythrocyte sedimentation, triglycerides, immunoglobulin A and beta 2-microglobulin in those patients with AIDS. CONCLUSION: AIDS patients present very significant differences in ten laboratory parameters, compared to the asymptomatic HIV infected patients. The follow up of these parameters may have prognostic value of AIDS evolution and be useful for the therapeutic decision making.

Acquired Immunodeficiency Syndrome↗