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PubMed2002

Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure.

The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environment. This was the rationale for the design of structured ARV treatment interruption (STI) studies for the management of HIV-1 patients with treatment failure. We have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI in patients with treatment failure due to ARV drug resistance. Plasma and peripheral blood mononuclear cell samples were obtained the day of treatment interruption (day 0) and 30 and 60 days afterwards. HIV-1 pol and env were partially amplified, cloned, and sequenced. At day 60 drug-resistant variants were replaced by completely or partially sensitive quasispecies. Phylogenetic analyses of pol revealed that drug-sensitive variants emerging after STI were not related to their immediate temporal ancestors but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than leading to the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen, as deduced from env sequences. This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure.

Adult↗

PubMed2001

Survey of reverse transcriptase from the heterosexual epidemic of human immunodeficiency virus type 1 CRF01_AE in Thailand from 1990 to 2000.

Genetic diversity of the HIV-1 envelope gene has shown a steady increase over time in the Thai and other regional epidemics. A serial survey of subtype CRF01_AE polymerase gene (RT) diversity in Thailand was performed, using 48 novel and 15 reported sequences covering the period 1990--2000. These sequences were gathered from individuals whose sole risk factor for infection was heterosexual contact. By contrast to envelope, diversity was low and, despite a 40% increase early in the epidemic, has remained static since 1996. These results indicate that epidemic HIV-1 may be constrained within defined limits of genetic diversity at least in some genomic regions.

Amino Acid Sequence↗

PubMed2006

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1.

BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.

Bayes Theorem↗

PubMed1996

[Cancer of the lung in patients with HIV infection].

OBJECTIVE: To know the characteristics of lung cancer among patients with HIV-1 infection. METHOD: The clinical records of patients infected with HIV-1 and lung cancer diagnosed at our institution from January 1991 to April 1995 were reviewed. The epidemiological, clinical, histological and evolutive factors were studied. RESULTS: A total of 1,258 patients were diagnosed of HIV-1 infection during that period of time. Seven patients out of those 1,258 had also a lung cancer. Six were males. All of them were smokers and had severe immunodepression. In four cases the histological diagnosis was epidermoid carcinoma, in two adenocarcinoma, and in one case undifferentiated large cell carcinoma. Five patients were on advanced stages at diagnosis, and lung cancer was the direct cause of death. CONCLUSION: The frequency of lung cancer among our patients with HIV-1 infection was 5.5 per thousand, with predominance of epidermoid carcinoma.

Adult↗

PubMed2004

Acute myocardial infarction in patients infected with human immunodeficiency virus.

BACKGROUND: Recent clinical and post-mortem reports suggests that human immunodeficiency virus (HIV) infection may participate in the process of atherosclerosis independent of other coronary risk factors. In this prospective and observational study, we investigated whether an associative link exists between HIV infection and coronary artery disease. METHODS: Of 690 patients admitted to our hospital in a 3-year period, 29 patients (28 men and 1 woman) with a mean age of 46 +/- 10 years had an acute myocardial infarction (AMI) on the basis of acute prolonged chest pain, ischemic electrocardiogram abnormalities, and elevated serum markers of myocardial necrosis at presentation. RESULTS: ST-segment elevation MI was present in 15 patients, and non-ST-segment elevation MI was present in 14 patients. Twenty-two patients (76%) were <55 years; 17 of these patients had no or 1 coronary risk factor, and 5 patients had 2 or 3 risk factors. Five patients >55 years had 1 coronary risk factor, and 2 patients had 2 risk factors. Thirteen patients underwent a myocardial revascularization procedure, and 1 patient died during hospitalization. CONCLUSIONS: HIV infection, as a cause of endothelial injury, may initiate the inflammatory process of early atherosclerosis and participate in the evolution of the atherothrombotic lesion responsible for AMI. This study suggests that the association of HIV infection and acute coronary syndrome may be more common than previously reported and underscores the need for further clinical studies.

Adult↗

PubMed2005

HIV-1 chemokine coreceptor utilization in paired cerebrospinal fluid and plasma samples: a survey of subjects with viremia.

BACKGROUND: Chemokine receptors serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine central nervous system infection pathogenesis. Using an in vitro functional entry assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid (CSF) and plasma in 46 subjects. METHODS: Paired CSF and plasma samples were selected from subjects with a range of CD4 T cell counts. Amplified populations of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for viral tropism and phylogeny. RESULTS: CSF and plasma pairs were mainly concordant for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma. Although R5+X4 tropism was associated with advanced immunodeficiency, all 4 subjects with acquired immunodeficiency syndrome dementia complex had R5 tropism in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and X4 viruses and viruses able to utilize either coreceptor, suggesting both virus exchange between compartments and autonomous CSF virus evolution. CONCLUSIONS: Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize CXCR4 are also present. Discordant tropism in CSF and plasma may have implications for R5 inhibitor therapy.

AIDS Dementia Complex↗

PubMed2003

Analysis of NCp7-dependent activation of HIV-1 cDNA integration and its conservation among retroviral nucleocapsid proteins.

HIV-1 nucleocapsid protein NCp7 is a small basic protein with two zinc fingers, found in the virion core where several hundred molecules coat the genomic RNA. NCp7 has nucleic acid chaperone properties that guide reverse transcriptase (RT) to synthesize the proviral DNA flanked by the long terminal repeats (LTR). In vitro, NCp7 can strongly activate magnesium-dependent LTR-DNA strand transfer by integrase (IN). Here we show that IN activation relies on both the basic residues and the zinc fingers of NCp7. NCp7 lacking the zinc fingers binds DNA but moderately stimulates strand transfer by IN. The NCp7 zinc-finger domain binds DNA poorly and does not efficiently stimulate IN activity. However, the NC zinc-finger domain can complement DNA binding to restore full activation of strand transfer by IN. We propose that the basic residues and the zinc fingers function together to stabilize IN at the LTR ends and promote the formation of a nucleoprotein complex competent for integration. We also show that these properties of HIV-1 NCp7 are remarkably conserved among nucleocapsid proteins of retrotransposon and retrovirus origins.

Amino Acid Sequence↗

PubMed1998

Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance.

Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. In the absence of drugs, the replication rate of all infectious clones generated was comparable to that of wild type HIV-1. However, in the presence of zidovudine or didanosine, the comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151) > HIV-1(75/77/116/151) approximately HIV-1(151), whereas that for drug resistance was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) > or = HIV-1(77/116/151) > HIV-1(151). The virologic features of these infectious mutants suggest that HIV-1 develops drug resistance through one or more mutations, which, however, sacrifice replicative capability; then it finally acquires optimal replication competence by additional mutations when the multi-dideoxynucleoside-resistant mutant emerges.

Animals↗

PubMed1996

The HIV/AIDS epidemic: its evolutionary implications for human ecology with special reference to the immune system.

The epidemiology of AIDS in Africa is discussed. Serological and clinical data on virology and population genetics are related to current theories of heterosexual transmission and to cultural practices involving the exchange or transmission of body fluids between individuals, such as female and male genital mutilation and indigenous or 'folk' medicine, as well as non-Western medical uses of medical syringes. A review of the relationship of autoimmune conditions, graft-vs-host disease and the retrovirus/oncogene involvement is presented. These data place in a new perspective concepts of widespread heterosexual infection and transmission of HIVs as well as their relation to AIDS in the context of the evolution of the human immune system.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Interaction with simian Hck tyrosine kinase reveals convergent evolution of the Nef protein from simian and human immunodeficiency viruses despite differential molecular surface usage.

Simian and human immunodeficiency virus type 1 (SIV and HIV-1) Nef proteins are thought to use different molecular surfaces to mediate the protein-protein interactions required for their otherwise similar functions. This genetically separable function suggests convergent evolution of primate lentiviruses and/or structural differences between human and nonhuman primate cellular target proteins. However, such comparative molecular analyses have not been undertaken so far using the respective natural host-derived cellular targets. We cloned simian Src family kinase Hck and analyzed structurally and biochemically its interaction with SIV Nef.

Amino Acid Sequence↗

PubMed1998

Measuring health-related quality of life among patients infected with human immunodeficiency virus.

Optimizing health-related quality of life (HRQL) has become an important treatment focus for patients infected with human immunodeficiency virus (HIV). Consideration of HRQL is especially relevant with the development of new antiretroviral agents that have significant side effects. The measurement of HRQL is still in evolution, and several methods have been used to quantify HRQL in the HIV-infected population. A review of existing studies shows that HRQL scores do not always correlate with disease stage or health indices and that symptoms have a significant impact on HRQL. Studies have also revealed that certain therapies for HIV and opportunistic infections exact a significant cost in terms of HRQL. HRQL outcomes will play a major role in treatment decisions for HIV-infected patients and in the development and marketing of new pharmaceutical agents in the near future.

HIV Infections↗

PubMed2006

[Central nervous system HIV-associated polyarteritis nodosa: long-term outcome].

INTRODUCTION: HIV-associated vasculitis is an infrequent entity, and only few data about its long-term evolution is available. EXEGESIS: We report the long-term outcome of a patient with central nervous system HIV-associated periarteritis nodosa and then discuss the therapeutic options for this class of vasculitis. CONCLUSION: This observation highlights the role of HAART in the treatment of HIV-associated vasculitis. Persistent remission can be obtained when viral replication is under control.

Adult↗

PubMedDate not supplied

Integrating health care for women diagnosed with HIV infection, substance abuse, and mental illness in Detroit, Michigan.

This article describes the evolution of Personalized Nursing, a comprehensive nursing practice model of care. Findings from several nursing research studies contributed to the development of Personalized Nursing. The model includes a practice model of the art of nursing care based on nursing theory and a specific nursing process that directs nursing care delivery. The process of care delivery includes location of hard-to-reach clients; linkage to health care providers; integration of care among providers for clients diagnosed with HIV, mental illness, and substance abuse; and strategies to promote retention in health care. Use of Personalized Nursing is designed to assist clients to improve their well-being and increase positive health-related behaviors. Personalized Nursing has been used in urban landscapes to serve multiply diagnosed clients at risk for HIV infection. The model is currently being used in a study targeting multiply diagnosed women who are lost to follow-up from medical care.

Community Health Nursing↗

PubMed2004

The conserved carboxy terminus of the capsid domain of human immunodeficiency virus type 1 gag protein is important for virion assembly and release.

The retroviral Gag precursor plays an important role in the assembly of virion particles. The capsid (CA) protein of the Gag molecule makes a major contribution to this process. In the crystal structure of the free CA protein of the human immunodeficiency virus type 1 (HIV-1), 11 residues of the C terminus were found to be unstructured, and to date no information exists on the structure of these residues in the context of the Gag precursor molecule. We performed phylogenetic analysis and demonstrated a high degree of conservation of these 11 amino acids. Deletion of this cluster or introduction of various point mutations into these residues resulted in significant impairment of particle infectivity. In this cluster, two putative structural regions were identified, residues that form a hinge region (353-VGGP-356) and those that contribute to an alpha-helix (357-GHKARVL-363). Overall, mutations in these regions resulted in inhibition of virion production, but mutations in the hinge region demonstrated the most significant reduction. Although all the Gag mutants appeared to have normal Gag-Gag and Gag-RNA interactions, the hinge mutants were characterized by abnormal formation of cytoplasmic Gag complexes. Gag proteins with mutations in the hinge region demonstrated normal membrane association but aberrant rod-like membrane structures. More detailed analysis of these structures in one of the mutants demonstrated abnormal trapped Gag assemblies. These data suggest that the conserved CA C terminus is important for HIV-1 virion assembly and release and define a putative target for drug design geared to inhibit the HIV-1 assembly process.

Amino Acid Sequence↗

PubMed2002

HIV type 1 group M clades infecting subjects from rural villages in equatorial rain forests of Cameroon.

Though the HIV-1 subtypes infecting patients living in urban and semi-urban areas in Cameroon have been reported, information on the subtypes infecting patients in rural villages is lacking. To begin to understand the diversity of the HIV-1 group M subtypes infecting persons living in rural villages in the equatorial rain forest regions of Cameroon, 49 plasma samples from 14 rural villages in four provinces of Cameroon were analyzed using heteroduplex mobility analysis (HMA), DNA sequencing, and phylogenetic tree analysis on the basis of env C2V5, gag, or pol regions. Sixty-one percent of the group M infections were clade A or CRF02_AG-like as subtyped by env and gag. Of the remaining group M infections, 12% were either A or CRF02_AG-like or CRF01_AE-like in recombination with other clades; 25% were infections that were entirely non-A or non-CRF02_AG-like; and 2% were CRF11_cpx. The HIV-1 group M clades identified included A, D, F (F2), G, and H. The CRF strains identified were CRF02_AG-like, CRF01_AE-like, and CRF11_cpx. Two new intersubtype recombinant infections, H/G and A/F2, were identified. This study suggests that the HIV-1 diversity in rural villages in the equatorial rain forest of Cameroon is at least as broad as has been observed in major cities of Cameroon and that multiple HIV-1 group M subtypes are infecting persons living in the countryside of Cameroon.

Adolescent↗

PubMed2002

Differential selection of specific human immunodeficiency virus type 1/JC499 variants after mucosal and parenteral inoculation of chimpanzees.

Regardless of the route of transmission, it is generally accepted that the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted from an infected individual to an uninfected individual is genetically homogeneous. This finding and the observation that HIV-1 genotypes in recipients are minor variants in the donors suggest strongly that selection for specific variants occurs. However, most analyses have been limited to the V3 region of env. In addition, the exact time at which most new infections occurred was not known, making it almost impossible to analyze virus populations present in donor-recipient pairs at the time of HIV-1 transmission. To circumvent this problem, three chimpanzees were inoculated with a genetically defined stock of cell-free HIV-1/JC499 by one of three routes: intravenously or via the cervical or penile mucosa. PCR products of the C2-to-V5 region of env were amplified from both proviral DNA and virion RNA in blood samples collected soon after infection and were screened by heteroduplex analysis (HDA). Those PCR products with distinct HDA banding patterns were cloned and sequenced. In all three animals, transmitted variants encoded one of two V3-loop populations identified in the inoculum, indicating relative homogeneity in this region. However, different virus populations, defined by combinations of specific V4 and V5 sequences, were found when variants in the animal inoculated intravenously (at least 13 V4-plus-V5 combinations) were compared with those in the two animals inoculated by the mucosal routes (limited to only four V4-plus-V5 combinations). The only V4-plus-V5 population in variants found in all three chimpanzees was the major population in the inoculum, which contained viruses with more than 30 different V4-plus-V5 combinations. That the majority of the V4-plus-V5 genotypes in variants transmitted to all three animals were minor populations in the inoculum indicated that selective transmission defined by the V4-plus-V5 regions had occurred but that distinct populations were transmitted by parenteral versus mucosal routes. These results indicate that the putative homogeneity of HIV-1 variants in a newly infected individual might be an artifact of the region of the env gene evaluated and that regions other than V3 might play a major role in selective transmission.

Amino Acid Sequence↗

PubMed2004

[Sequence variation of HIV and bioinformatics].

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) interacts with receptors on the target cell and mediates virus entry by fusing the viral and cell membranes. To maintain the viral infectivity, amino acids that interact with receptors are expected to be more conserved than the other sites on the protein surface. In contrast to the functional constraint of amino acids for the receptor binding, some amino acid changes in this protein may produce antigenic variations that enable the virus to escape from recognition of the host immune system. Therefore, both positive selection (higher fitness) and negative selection (lower fitness) against amino acid changes are taking place during evolution of surface proteins of parasites To elucidate the evolutionary mechanisms of the whole HIV-1 gp120 envelope glycoprotein at the single site level, we collected and analyzed all available sequence data for the protein. By analyzing 186 sequences of the HIV-1 gp120 (subtype B), we reevaluated amino acid variability at the single site level, and estimated the numbers of synonymous and nonsynonymous substitutions at each codon position to detect positive and negative selection. We identified 33 amino acid positions which may be under positive selection. Some of these positions may form discontinuous epitopes. We also analyzed amino acid sequences to find amino acid positions responsible for usage of the second receptor. We found that, in addition to the V3 loop, amino acid variation at residue 440 in C4 region is clearly linked with the usage of CXCR 4.

Amino Acid Sequence↗

PubMedDate not supplied

[Oral manifestations in AIDS or HIV infection. Bibliographic update].

AIDS is a systemic infection that in many steps of its evolution presents various oral lesions and clinical conditions. This fact raises a problem for the dentist who are working on heterogeneous populations of healthy and infected people as well as on AIDS patients: to receive a continuous update about the disease. Apart from the risks of exposure inherent to his personal relation with HIV-infected or AIDS patients, the dentist is one of the health careworkers who must and ought recognize the oral signs of the disease when they appear in the mouth. For this reason this paper describes recent data on oral findings in AIDS: fungal, viral and bacterial infections, neoplasms and other manifestations of unknown or rare etiology. The most precocious clinical or pathological characteristics of these oral diseases suggesting HIV-infection or its results, are also stressed when described. Some doubts are possessed here about the meaning of outstanding oral AIDS lesions as "hairy leukoplakia". On the other way diagnostic methods which can help to recognize this lesion are also commented.

Acquired Immunodeficiency Syndrome↗