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PubMed1996

Comparative histopathological study of pulmonary tuberculosis in human immunodeficiency virus-infected and non-infected patients.

SETTING: Clinical features of human immunodeficiency virus (HIV)-associated tuberculosis depend upon the patients' residual immunity. An immune-dependent presentation has also been described at the histopathological level in many extra-pulmonary sites, but no descriptions have so far been made on the histopathology of HIV-associated pulmonary tuberculosis. OBJECTIVE: To compare the histopathological features of pulmonary tuberculosis in HIV-infected subjects and seronegative patients. DESIGN: We carried out a retrospective comparative study on 16 HIV-infected subjects and 16 seronegative patients with culture-proven pulmonary tuberculosis who underwent transbronchial biopsy. We evaluated the bacillary burden and the parenchymal inflammatory reaction by means of a four-graded scoring system giving an approximate quantitative measure of the two parameters. RESULTS: HIV-associated pulmonary tuberculosis was found to differ significantly from disease forms seen in seronegative patients, with a significant tendency to develop highly bacillary and poorly reactive histopathological pictures along with the downgrading evolution of immune function. CONCLUSION: Pathologic features of pulmonary tuberculosis in HIV-infected subjects differ from those encountered in seronegative patients depending upon the individual immunity of the former. HIV-associated progressive depletion of CD4+ lymphocytes leads to substantial changes in pulmonary reactivity to Mycobacterium tuberculosis; multibacillary pictures in a background of loose inflammatory reactions are quite common findings at the extreme phase of HIV-related immune deterioration.

AIDS-Related Opportunistic Infections↗

PubMed2004

Analysis of near full-length genome sequences of HIV type 1 BF intersubtype recombinant viruses from Brazil reveals their independent origins and their lack of relationship to CRF12_BF.

We analyze the recombinant structures and phylogenetic relationships of nine near full-length genome sequences of HIV-1 BF intersubtype recombinant viruses from Brazil, eight of them newly derived. These were obtained by PCR amplification from peripheral blood mononuclear cells (PBMCs) DNA or PBMCs culture supernantant RNA. The recombinants exhibited unique mosaic structures, except two viruses with a single near coincident breakpoint. Comparison with CRF12_BF revealed only two coincident breakpoints in two recombinants. Phylogenetic analyses failed to support a common ancestry of Brazilian recombinants or their relationship to CRF12_BF, which widely circulates in Argentina. Intersubtype breakpoint distribution along the genome was uneven, with the highest mean frequency in the polymerase domain of reverse transcriptase, and the lowest in env. These results indicate that HIV-1 BF recombinants from Brazil have independent origins and are unrelated to CRF12_BF, and that intersubtype breakpoints are frequent in pol segments analyzed for drug resistance detection.

Brazil↗

PubMed2005

Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l.

OBJECTIVE: To analyse immunological markers associated with CD4+ lymphocyte T-cell count (CD4+) evolution during 12-month follow-up after treatment discontinuation. METHOD: Prospective observational study of chronically HIV-1 infected patients with CD4+ above 400 x 10(6) cells/l. RESULTS: CD4+ changes took place in two phases: an initial rapid decrease in the first month (-142 x 10(6) cells/l on average), followed by a slow decline (-17 x 10(6) cells/l on average) The second slope of CD4+ decline was not correlated with the first and only baseline plasma HIV RNA was associated with it. The decline in CD4+ during the first month was steeper in patients with higher CD4+ and weaker plasma HIV RNA baseline levels. Moreover, the decline was less pronounced (P < 10(-4)) in patients with CD4+ nadir above 350 x 10(6) cells/l (-65 x 10(6) cells/l per month) in comparison with those below 350 x 10(6) cells/l (-200 x 10(6) cells/l per month). A high number of dendritic cells (DCs) whatever the type was associated with high CD4+ at the time of treatment interruption and its steeper decline over the first month. Moreover, the myeloid DC level was stable whereas the lymphoid DC count, which tended to decrease in association with decrease in CD4+, was negatively correlated with the HIV RNA load slope. CONCLUSIONS: The results support the use of the CD4+ nadir to predict the CD4+ dynamic after treatment interruption and consideration of the CD4+ count after 1-month of interruption merely reflects the 12-month level of CD4+. Although DCs seem to be associated with the CD4+ dynamic, the benefit of monitoring them has still to be defined.

Adult↗

PubMed2002

Three-dimensional structural model analysis of the binding site of an inhibitor, nervonic acid, of both DNA polymerase beta and HIV-1 reverse transcriptase.

Previously, we reported the three-dimensional molecular interactions of nervonic acid (NA) with mammalian DNA polymerase beta (pol beta) [Mizushina et al. (1998) J. Biol. Chem. 274, 25599-25607]. By three-dimensional structural model analysis and comparison with the spatial positioning of specific amino acids binding to NA on pol beta (Leu11, Lys35, His51, and Thr79), we obtained supplementary information that allowed us to build a structural model of human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT). In HIV-1 RT, Leu100, Lys65, His235, and Thr386 corresponded to these four amino acid residues. These results suggested that the NA binding domains of pol beta and HIV-1 RT are three-dimensionally very similar. The effects of NA on HIV-1 RT are thought to be same as those on pol beta in binding to the rhombus of the four amino acid residues. NA dose-dependently inhibited the HIV-1 RT activity. For binding to pol beta, the kinetics were competitive when the rhombus was present on the DNA binding site. However, as the rhombus in HIV-1 RT was not present in the DNA binding site, the three-dimensional structure of the DNA binding site must be distorted, and subsequently the enzyme is inhibited non-competitively.

Amino Acid Sequence↗

PubMed1997

Molecular analyses of human immunodeficiency virus type 1 V3 region quasispecies derived from plasma and peripheral blood mononuclear cells of the first long-term-nonprogressing mother and child pair.

Molecular analyses were done for the V3 region quasispecies of human immunodeficiency virus type 1 (HIV-1) strains from plasma and peripheral blood mononuclear cells of the first HIV-1-infected long-term-nonprogressing mother-child pair whose members have survived for >13 years with stable CD4 T cell counts. There was a predominance of lower V3 loop charge and the absence of genotypic changes that are critical in phenotypic determination and tropism during HIV-1 infection. The intrahost genetic diversity between HIV-1 strains from the mother-child pair compared with HIV-1 strains from slow and rapid progressors suggested that a high genetic heterogeneity in HIV-1 strains from this HIV-1-infected long-term-nonprogressing mother and child pair was directly proportional to the length of their immunocompetent period.

Amino Acid Sequence↗

PubMed1994

Frequent and early HIV-1MN neutralizing capacity in sera from Dutch HIV-1 seroconverters is related to antibody reactivity to peptides from the gp120 V3 domain.

The temporal development of HIV-1 neutralizing activity and antibodies to the gp120-V3 neutralization domain were studied in sera from 20 Dutch HIV-1-infected individuals followed from seroconversion on. Serum neutralizing capacity was assessed with three T cell line-tropic isolates: HIV-1MN, HIV-1HXB2, and the patient isolate HIV-1(320). Neutralizing activity to HIV-1MN developed in 18 individuals (90%) within 0 to 10 months after seroconversion. Parallel evolution of IgG reactivity to V3 peptides of United States/European type variants, and the capability of such peptides to completely inhibit HIV-1MN neutralization in four of five tested sera (taken 1-2 years after seroconversion), indicate that a large proportion of HIV-1MN neutralizing antibodies is directed to V3. The early appearance and high frequency of HIV-1MN neutralizing activity in the Dutch study group indicate the close relationship of HIV-1MN to HIV-1 variants circulating in the Netherlands. Neutralizing activity to HIV-1HXB2 (in 15 of 20 individuals) developed several months after that to HIV-1MN in all individuals (average, 10 months after seroconversion) and was not seen in the absence of HIV-1MN neutralizing activity. Neutralizing activity to the Dutch isolate HIV-1(320) (found in 11 of 18 tested individuals) emerged simultaneously with that to HIV-1MN in 4 individuals but appeared later in 7. In most individuals, HIV-1HXB2 neutralization was not accompanied by reactivity to a V3 peptide from this strain, indicating that the extension of neutralizing activity to more divergent strains, which takes place at later stages, must be attributed to non-V3-directed antibodies.

Adult↗

PubMed2006

Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts.

Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).

Adult↗

PubMed1993

[Development of a factual model for the dynamics of the transmission of infection by the human immunodeficiency virus: an example for animal epidemiology].

In order to simulate the spreading mechanism of human immunodeficiency virus (HIV), a factual approach was developed given the ease of incorporating new knowledge and taking into account the variability of a large number of sociological, biological and demographic factors, and also on account of the dynamics of the relational network of individuals. By way of example, the model was applied to data concerning homosexuals in San Francisco (United States of America) between 1980 and 1987, which enabled an evaluation to be made of the probability of HIV transmission from each partner, using two hypotheses about the evolution of contagiousness of an infected individual during the incubation period. An analysis of the sensitivity of the model revealed certain factors which had a strong influence on the growth of the epidemic. Application of this technique to the entire population of France is planned.

Animals↗

PubMed2003

Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus.

To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.

Adult↗

PubMed2005

Bacillary angiomatosis caused by Bartonella quintana.

Bacillary angiomatosis is a disorder of neovascular proliferation involving skin and lymph nodes of immunosuppressed patients. Bartonella henselae or Bartonella quintana have been inculpated as causative by direct culture or PCR amplification of DNA sequences. Here, we report the clinical evolution of a patient infected with human immunodeficiency virus (HIV) whose B. quintana infection was diagnosed by PCR.

Angiomatosis, Bacillary↗

PubMedDate not supplied

[Fungemia by Candida non albicans in patients with HIV infection].

OBJECTIVE: To analyse candidemia by Candida non albicans in adult HIV-infected patients from 1989 to August 1998. PATIENTS AND METHODS: We retrospectively reviewed all HIV patients who presented at least one positive peripheral blood culture for Candida spp. Clinical, epidemiologic, immunologic and evolutive characteristics, and risk factors for candidemia were analysed. RESULTS: During this period of time, 2,025 HIV-infected patients were diagnosed. Five of them developed candidemia by C. albicans and 6 by C. non albicans. These last ones were all men with mean age of 32.1 years old, and intravenous drug use was the risk factor for HIV in 5 of them; aids had previously been diagnosed in 4 patients and 3 had receipt imidazoles. None was neutropenic. Three cases were nosocomially acquired. Median CD4 cell count was 108.6 x 10(6)/l (3-366). Candida krusei was isolated in two intravenous drug users, Candida parapsilosis in two other patients and Candida glabrata and Candida tropicalis in one of the other two cases each. We treated 2 patients with amphotericin B and 2 with fluconazole. One patient died. CONCLUSIONS: Candidemia is not frequent in HIV-infected patients. Candidemia by C. non albicans in HIV-infected patients presents similar characteristics as in other immunodepressed patients and it is fundamentally associated with previous use of imidazoles, nosocomial acquisition and late-stage aids. It is noteworthy that C. krusei was isolated in two intravenous drug users.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Dynamics of intrathecal immunoglobulin synthesis].

INTRODUCTION: Dynamics of the immune response in Central Nervous System (CSN) is different from the well-known switch of IgM synthesis to IgG synthesis in blood. OBJECTIVE: Broadcast the behavior and the factors involved in the dynamics of the intrathecal immune response in infectious neurological disorders. DEVELOPMENT: The lack of a switch from IgM class response to IgG response could be more related to regulation-modulation mechanisms of the CNS immune response than differs from blood in a different cytokines composition, and the possibility of chemokines synthesis during the neuroinflammatory process, and the neuroimmune-endocrine mechanisms. The immune pattern can be stable like neuroborreliosis, and can be modify like in herpes simplex meningoencephalitis. It could have a typical pattern like in Neisseria meningitidis meningoencephalitis and neurotuberculosis. Also the pattern could be still detectable for many years after sufficient treatment and complete recovery of the symptom-free patients like in neurosyphilis or an advanced precocious response during the childhood. In HIV encephalopathy the pattern remains the same during the evolution but in other virus infections, like Echo 6 or Coxsackie B5, depends on the biological agent. CONCLUSIONS: In order to know the acuity of the disease, we have to know the physiopathologic characteristics of the biological agents, time courses, locations of the pathological processes, and the host age. The main signs in cerebrospinal fluid of an acute, active disease of CNS are the increased of cerebrospinal fluid cell count and the increased of albumin ratio.

AIDS Dementia Complex↗

PubMed1992

[Pneumocystis carinii pneumonia in AIDS and prolonged fever].

Pneumonia by Pneumocystis carinii (NPC) presents a high incidence in the evolution of patients infected by the human immunodeficiency virus (HIV). Common clinical signs include fever, dry cough and dyspnea, in the presence of pulmonar interstitial affection with several degrees of hypoxemia. One hundred and sixteen patients with NPC and infection by HIV were diagnosed between December 1986 and January 1990. Criteria of persistent fever was established in 10 of them (8.7%), with normal thoracic radiography at the time of hospitalization. NPC in the adquired immunodeficiency syndrome (SIDA) may develop' with persistent fever, joining the large relation of entities manifesting in this way.

Acquired Immunodeficiency Syndrome↗

PubMed1997

[Chancroid in Algeria: the status of this sexually transmitted disease in 1995].

Absent for several decades, the chancroid reappeared in Algeria in 1988. In the unique department of Dermatology and Venereology of the University Hospital of the country of Tlemcen (more than 700,000 inhabitants), we wanted to know the state of this STD seven years after the report of the first cases. The file of the consulting patients were examined. We looked for the principal characteristics of this STD: age, sex, incubation period, place infection contact, type of relation, clinical presentation, evolution without and with treatment, other associated STD (syphilis, HIV). From August 1988 (1st case) to December 1995, 144 cases of chancroid were collected = 1988: 6, 1989: 5, 1990: 7, 1991: 18, 1992: 11, 1993: 33, 1994: 48, 1995: 16. The presentation is quite stereotyped; it concerns males only, singles in must cases, having had sexual relations with prostitutes. The incubation period is short (less than 10 days), the characteristic ulceration presents, very often, some adenopathies. The treatment by cotrimoxazole is efficient. They are no concomitant syphilis or HIV infection. The chancroid is the first cause of genital ulceration in the world. Since 1991, it is the principal STD in our department. It spreads within a male population, young singles associated with prostitutes. It is well installed in Algeria, and its role, although minor, in the transmission of the HIV infection, should not be neglected.

Adolescent↗

PubMedDate not supplied

Predicting HIV-1 coreceptor usage with sequence analysis.

Bioinformatics approaches are increasingly being used to identify and understand the genetic variation underlying changes in HIV-1 biological phenotype. The variable regions of the viral envelope are the major determinant of virus coreceptor usage and cell tropism. Specifically, amino acids 11 and 25 in the 3rd variable (V3) loop have been found to strongly influence viral syncytium inducing capacity and coreceptor usage. Many additional V3 loop changes, however, as well as changes elsewhere in Env, are thought to contribute to phenotype. In this review we describe several recently developed methods to analyze this variability and their use to predict biological phenotype based on sequence information. These approaches have identified changes in the V3 loop, in addition to the known changes at positions 11 and 25, that affect phenotype and significantly enhance our ability to predict phenotype from genotype. Besides improving phenotype prediction, methods that score V3 sequences on a continuous scale can also assist in the interpretation of evolutionary information about shifts in phenotype, and the relationship between that evolution and pathogenesis. Several examples and potential practical applications of this scoring are discussed. We conclude that advances in computational approaches have enhanced both our ability to predict and to understand HIV-1 biological phenotype evolution. Further development of these methods, by extending analysis to regions outside the V3 loop and to clades beyond subtype B, will extend our understanding of HIV-1 pathogenesis and inform treatment strategies.

Computational Biology↗

PubMed2006

Role of common human TRIM5alpha variants in HIV-1 disease progression.

BACKGROUND: The retroviral restriction factor tripartite motif protein (TRIM)5alpha, is characterized by marked amino acid diversity among primates, including specific clusters of residues under positive selection. The identification of multiple non-synonymous changes in humans suggests that TRIM5alpha variants might be relevant to retroviral pathogenesis. Previous studies have shown that such variants are unlikely to modify susceptibility to HIV-1 infection, or the course of early infection. However, the longterm effect of carrying Trim5alpha variants on disease progression in individuals infected with HIV-1 has not previously been investigated. METHODS: In a cohort of 979 untreated individuals infected with HIV-1 with median follow up 3.2 years and 9,828 CD4 T cell measurements, we analysed common amino acid variations: H43Y, V112F, R136Q, G249D, and H419Y. The rate of CD4 T cell decline before treatment was used as the phenotype. In addition, we extended previous work on the in vitro susceptibility of purified donor CD4 T cells (n = 125) to HIV-1 infection, and on the susceptibility of HeLa cells that were stably transduced with the different TRIM5 variants. Haplotypes were analysed according to the most parsimonious evolutionary structure, where two main human TRIM5alpha groups can be defined according to the residue at amino acid 136. Humans present both Q136 and R136 at similar frequency, and additional TRIM5alpha amino acid variants are almost exclusively derived from R136-carrying haplotypes. RESULTS: We observed modest differences in disease progression for evolutionary branches carrying R136-derived haplotypes, and with the non-synonymous polymorphisms G249D and H419Y. In vitro analysis of susceptibility of donor CD4 T cells, and of the various transduced HeLa cell lines supported the absence of significant differential restriction of HIV-1 infection by the various huTRIM5alpha alleles. CONCLUSION: Common human variants of TRIM5alpha have no effect or modest effect on HIV-1 disease progression. These variants occur at sites conserved throughout evolution, and are remote from clusters of positive selection in the primate lineage. The evolutionary value of the substitutions remains unclear.

Adult↗

PubMedDate not supplied

Genetic analyses of cis-acting sequences controlling expression of human immunodeficiency virus type 1 coreceptor-CCR5 gene in rabbits and CXCR4 gene in monkeys.

INTRODUCTION: Human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus all use chemokine receptors (CCR5, CXCR4, and minor receptors) to gain entry into a susceptible cell and establish infection successfully by way of membrane fusion. Many such chemokine receptors that can act as entry cofactors under in vitro conditions have been identified, but the roles of CCR5 and CXCR4 chemokine receptors in infection, tropism, and pathogenesis have been studied in greater detail. The promoter region of CCR5 gene is quite polymorphic in humans, and mutations that affect the progression of HIV-1 have been identified. STUDY DESIGN/METHODS: We studied the nature of mutations in the CCR5 promoter region in rabbits. Large number of mutations, deletions, substitutions, and point mutations were observed all along the 400 base pair region of the promoter. RESULTS: We show that rabbit CCR5 promoter possesses features common to both humans and monkeys and lacks the second highly polymorphic region B in the CCR5 promoter that was previously identified in monkeys. Besides providing important evolutionary information, our findings can directly make an impact on the known expression levels of CCR5 protein that can modulate the progression of HIV-1 in rabbits. The CXCR4 promoter of monkeys showed polymorphisms that were largely caused by single nucleotide changes when compared with humans. CONCLUSIONS: This distinctly different evolutionary pattern suggests a more important role for chemokine receptor-CCR5 in the host defense.

Animals↗

PubMed1999

Antibodies from HIV-positive and AIDS patients bind to an HIV envelope multivalent vaccine.

A major problem impeding development of an effective HIV vaccine is the rapid antigenic variability that is characteristic of several envelope glycoprotein epitopes. Frequent mutations alter the composition of the most immunogenic regions of the envelope glycoprotein. We have prepared a synthetic immunogen representing the evolution of the major hypervariable epitopes on the envelope glycoprotein (gp120) of HIV-1. Five synthetic constructs, representing each of the HIV-1 gp120 hypervariable epitopes were tested for recognition by antibodies from patients infected with HIV-1 from different geographic regions worldwide. An HIV-1 human plasma panel provided a representation of the antibodies recognizing subtype-specific epitope sequences prevalent at different parts of the world. The vaccine construct was recognized by antibodies from HIV-1-positive individuals infected with subtypes A, B, C, D, E, and F. Antibodies in pooled HIV-1 patient sera from San Francisco also recognized all five constructs. This complex immunogen was recognized by antibodies in sera from individual HIV-1-positive and AIDS patients from Puerto Rico and Canada, with a strong binding to the complete vaccine and the V3 component. Altogether, our results demonstrate that antibodies from seropositive patients infected with different HIV-1 clades recognize and bind to the HIV hypervariable epitope construct vaccine preparation and its individual components.

AIDS Vaccines↗