PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “HIV evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2004

Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy.

BACKGROUND: Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach. OBJECTIVES: We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil. STUDY DESIGN: Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline. RESULTS: Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes. CONCLUSIONS: These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children.

Adolescent↗
PubMed2006

[HIV drug resistance].

HIV drug resistance can be defined as any change (in protease, reverse transcriptase gene or envelope protein) that improves viral replication in the presence of an inhibitor. One of the most important causes of treatment failure is the development of resistance to antiretrovirals by HIV. Resistance studies have highlighted distinct evolution patterns of mutations and cross resistance among drug classes, which have the ability to impact on the choice of subsequent salvage treatment. A number of resistance testing technologies have been developed to measure HIV drug resistance and prospective studies have shown that the use of these resistance tests have the ability to improve the virological response to a salvage regimen. These tests are now widely used in developed countries and are recommended in case of therapeutic failure in treated patients and in case of recent infection in naive patients.

Anti-Retroviral Agents↗
PubMed2006

Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein.

BACKGROUND: We previously described the selection of a T20-dependent human immunodeficiency virus type-1 (HIV-1) variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope (Env) protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env (GIA-SKY), creating a protein that undergoes a premature conformational switch, and the presence of T20 prevents this premature switch and rescues viral entry. In the present study, we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20, with the aim to identify second site compensatory changes, which may provide new mechanistic insights into Env function and the T20-dependence mechanism. RESULTS: Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R). This mutation was sufficient to abolish the T20-dependence phenotype and restore viral replication in the absence of T20. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. The escape variant was also less sensitive to soluble CD4, suggesting a reduced CD4 receptor affinity. CONCLUSION: The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY) can be corrected by a second site mutation in Env (GIA-SKY-G431R) that affects the interaction with the CD4 receptor.

Amino Acid Sequence↗
PubMed2003

The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection.

Cellular viral reservoirs and anatomic sanctuary sites allow continuing HIV-1 replication in patients with suppressed plasma viremia who are receiving highly active antiretroviral therapy and prevent eradication of HIV-1 by these regimens. Cells of macrophage lineage, including monocytes subsets within the blood, play a role in HIV-1 persistence. Evidence of sequence evolution in blood monocytes, in comparison to resting CD4+ T cells, demonstrates their distinct contribution to plasma viremia. There is evidence to suggest that a specific monocyte subset, of CD14loCD16hi phenotype, is more susceptible to HIV-1 infection than the majority of blood monocytes. Trafficking of monocytes through various tissues following their emigration from the bloodstream allows these cells to differentiate into tissue macrophages, or potentially to egress from the tissues as migratory dendritic cells. This review provides an evaluation of the contribution of monocytes to HIV-1 persistence and the HIV-1 reservoir, essential for the effective design of therapeutic eradication strategies.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

Metabolic evaluation of HIV-infected patients receiving a regimen containing lopinavir/ritonavir (Kaletra).

PURPOSE: We have analyzed retrospectively the evolution of metabolic parameters in a cohort of 159 HIV-infected patients taking a lopinavir/ritonavir-containing regimen during a mean period of 15 months. METHOD: This study was completed by an additional evaluation after strict 12 hours fasting of total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG), glucose, and insulin levels in a subset of 100 patients from the cohort. RESULTS: TC and TG levels increased early after introduction of lopinavir/ritonavir, but remained subsequently stable. After a median of 15 months, TC was greater than normal laboratory range in 46% of cases and TG levels were greater than normal laboratory range in 52% of cases. However, in nearly 90% of these cases, elevations were less than or equal to grade 2. These increases were dependant on CDC stage and lipid levels at lopinavir/ritonavir initiation. No impact on glucose metabolism was found. CONCLUSION: These results are particularly reassuring for the use of lopinavir/ritonavir in everyday practice.

Adult↗
PubMed2001

A multiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics.

Rapidly evolving entities, such as viruses, can undergo complex genetic changes in the face of strong selective pressure. We have developed a modified heteroduplex tracking assay (HTA) capable of detecting the presence of single, specific mutations or sets of linked mutations. The initial application of this approach, termed multiple-site-specific (MSS) HTA, was directed toward the detection of mutations in the HIV-1 pro gene at positions 46, 48, 54, 82, 84, and 90, which are associated with resistance to multiple protease inhibitors. We demonstrate that MSS HTA is sensitive and largely specific to all targeted mutations. The assay allows the accurate and reproducible quantitation of viral subpopulations comprising 3% or more of the total population. Furthermore, we used MSS HTA in longitudinal studies of pro gene evolution in vitro and in vivo. In the examples shown here, populations turned over rapidly and more than one population was present frequently. To demonstrate the versatility of MSS HTA, we also constructed a probe sensitive to changes at positions 181 and 184 of the RT coding domain. Changes at these positions are involved in resistance to nevirapine and 2',3'-dideoxy-3'-thiacytidine (3TC), respectively. This assay easily detected the evolution of resistance to 3TC. MSS HTA provides a rapid and sensitive approach for detecting the presence of and quantifying complex mixtures of distinct genotypes, including genetically linked mutations, and, as one example, represents a useful tool for following the evolution of drug resistance during failure of HIV-1 antiviral therapy.

Antiviral Agents↗
PubMed2004

MinPD: distance-based phylogenetic analysis and recombination detection of serially-sampled HIV quasispecies.

A new computational method to study within-host viral evolution is explored to better understand the evolution and pathogenesis of viruses. Traditional phylogenetic tree methods are better suited to study relationships between contemporaneous species, which appear as leaves of a phylogenetic tree. However, viral sequences are often sampled serially from a single host. Consequently, data may be available at the leaves as well as the internal nodes of a phylogenetic tree. Recombination may further complicate the analysis. Such relationships are not easily expressed by traditional phylogenetic methods. We propose a new algorithm, called MinPD, based on minimum pairwise distances. Our algorithm uses multiple distance matrices and correlation rules to output a MinPD tree or network. We test our algorithm using extensive simmulations and apply it to a set of HIV sequence data isolated from one patient over a period of ten years. The proposed visualization of the phylogenetic tree\network further enhances the benefits of our methods.

Algorithms↗
PubMed2001

Using human immunodeficiency virus type 1 sequences to infer historical features of the acquired immune deficiency syndrome epidemic and human immunodeficiency virus evolution.

In earlier work, human immunodeficiency virus type 1 (HIV-1) sequences were analysed to estimate the timing of the ancestral sequence of the main group of HIV-1, the virus that is responsible for the acquired immune deficiency syndrome pandemic, yielding a best estimate of 1931 (95% confidence interval of 1915-1941). That work will be briefly reviewed, outlining how phylogenetic tools were extended to incorporate improved evolutionary models, how the molecular clock model was adapted to incorporate variable periods of latency, and how the approach was validated by correctly estimating the timing of two historically documented dates. The advantages, limitations, and assumptions of the approach will be summarized, with particular consideration of the implications of branch length uncertainty and recombination. We have recently undertaken new phylogenetic analysis of an extremely diverse set of human immunodeficiency virus envelope sequences from the Democratic Republic of the Congo (the DRC, formerly Zaire). This analysis both corroborates and extends the conclusions of our original study. Coalescent methods were used to infer the demographic history of the HIV-1 epidemic in the DRC, and the results suggest an increase in the exponential growth rate of the infected population through time.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[The acquired immunodeficiency syndrome in the elderly].

Three cases of AIDS in patients older than 60 years of age are presented and are characterized by the delay in diagnosis even in the face of suggestive clinical manifestations because of the lack of suspicion leading to fatal short term evolution in all the cases. The importance of HIV infection and its characteristics at this age are discussed. Transfusion is the most frequent method of transmission. The clinical manifestations do not differ from those of other ages with neurological and psychiatric manifestations being significant as a form of presentation. Evolution is usually rapidly progressive. The need to suspect HIV infection is emphasized in elderly patients when presenting typical AIDS pathology or atypical dementia or rapid evolution specially if pertaining to a risk group.

AIDS Dementia Complex↗
PubMed2004

Influence of random genetic drift on human immunodeficiency virus type 1 env evolution during chronic infection.

Human immunodeficiency virus type 1 (HIV-1) has high replication and mutation rates that generate large census populations and high levels of genetic variation. We examined the roles of natural selection, population growth, random genetic drift, and recombination in shaping the variation in 1509 C2-V5 env sequences derived from nine men with chronic HIV-1 infection. These sequences were obtained from clinical visits that reflect the first 6-13.7 years of infection. Pairwise comparisons of nonsynonymous and synonymous distances, Tajima's D test, Fu and Li's D* test, and a test of recurrent mutation revealed evidence for episodes of nonneutral evolution in a total of 22 out of 145 blood samples, representing six of the nine individuals. Using three coalescent-based maximum-likelihood estimators, we found viral effective population sizes in all nine individuals to be approximately 10(3). We also show that a previous estimate of the effective population size of approximately 10(5) based on rare haplotype frequencies decreases to approximately 10(3) upon correcting a biased sampling procedure. We conclude that the genetic variation in these data sets can be explained by a predominance of random genetic drift of neutral mutations with brief episodes of natural selection that were frequently masked by recombination.

Base Sequence↗
PubMed1992

[Fever of unknown origin in a cohort of HIV-positive patients].

The purpose of this study was to determine the prevalence of fever of unknown origin (FUO) in a cohort of HIV positive patients and to describe their evolution and the final diagnosis. The clinical records of 412 patients followed from January 1987 to December 1990 at our HIV outpatient clinic were reviewed: in 151 patients 255 episodes of fever had been observed of which 22 (in 21 patients) met the criteria for FUO. 19 patients (90%) presented with a CDC/WHO stage IV HIV infection and the mean CD4+ lymphocyte count was 0.160 G/l. The etiology was ultimately determined in 13/22 episodes (3 Pneumocystis carinii pneumonia, 3 invasive infections due to atypical mycobacteria, 2 bacterial pneumonia, 1 Cytomegalovirus colitis, 1 Isospora belli enteritis, 1 visceral leishmania, 1 candida septicemia and 1 lymphoma). In 6/22 episodes, the fever subsided after zidovudine was started and was therefore attributed to HIV itself. In 3/22 episodes no etiology was found. In conclusion, this series shows that FUO is usually seen in advanced HIV infection and that it often represents an early sign of opportunistic infection. This observation underlines the importance of follow-up, since it finally served to detect the etiology of FUO in 86% of cases. Trial treatment with zidovudine can be useful where no pathology has been discovered despite 3 weeks' follow-up and appropriate investigations.

AIDS-Related Opportunistic Infections↗
PubMed2006

Rapid progression of carotid lesions in HAART-treated HIV-1 patients.

To obtain data on the evolution of carotid lesions, we evaluated 133 patients at their first antiretroviral regimen, followed for at least 2 years; 77 treated with protease inhibitors (PIs): Group A and 56 with non-nucleosidic reverse transcriptase inhibitors (NNRTIs): Group B. All patients were subjected to carotid ultrasonography. In Group A, among the previously normal patients 22.5% developed lesions, 40% remained normal, 37.5% shifted to other antiretroviral regimens. Among the 37 previously pathologic patients, 46% worsened, 19% were stable, in 8% the lesions had disappeared, 27% shifted. In Group B, among the previously normal patients, 12.7% developed lesions, 80.8% remained unaltered, 6.5% shifted. Among the previously pathologic patients, 12.5% worsened, lesions reversed in 25%, remained stable in 50% and 12.5% shifted to PI. At statistical analysis, in Group A both the percentage of patients developing new lesions and the percentage of patients who worsened was significantly higher. In conclusion, we evidenced a more rapid onset of lesions in patients treated with PIs with respect to patients treated with NNRTIs and towards a more rapid evolution of the previous lesions. The shift from PIs to NNRTI/3 NRTI seems related to a lower rate of evolution. Interestingly, a disappearance of lesions was detected in both groups.

Acquired Immunodeficiency Syndrome↗
PubMed2004

[Characteristics and evolution of consultants, their risk factors and their behavior at the free anonymous HIV screening center of Colmar (France)].

INTRODUCTION: Data collected in free anonymous HIV screening centers (Centre d'Information et de Dépistage Anonyme et Gratuit du VIH, CIdAG) are numerous but poorly exploited. The characteristics of the consultants, their risk factors and their behavior were rarely analyzed previously. MATERIAL AND METHODS: Data of 3995 patients attending the CIdAG of Colmar between January 93 and February 99 were prospectively analyzed. Two 18-month periods at the beginning and end of the study were compared. RESULTS: The activity of the center was stable. Nine HIV infections were detected (2 p. 1000 consulting). The male/female ratio was 1.2 and the mean age was 26 years. The proportion of very young patients (<20 years) was 30 p. 100 and increased significantly between the two periods. Six per cent of the consultants were male homo/bisexuals and 2 p. 100 used intravenous drugs. A regular use of condoms when having occasional sexual relations was reported by 40 p. 100 of consultants before 20 years of age, but this proportion decreased regularly as the age increased. It was minimal among intravenous drug users (19 p. 100), and greater among male homo/bisexuals (46 p. 100) than among male heterosexuals (37 p. 100) and women (33 p. 100). This proportion increased significantly during the study period in heterosexual men and women but not in male homo/bisexuals. The number of sexual partners did not vary but the knowledge of the partners'status for HIV infection and drug addiction progressed significantly. Some subjects who attended the centre several times were identified anonymously. They differed from the other consultants by an older age (mean: 31), a higher proportion of male homo/bisexuals (14 p. 100) and a less regular use of condom (26 p. 100). COMMENTS: In some French anonymous HIV screening centers, information and prevention currently appears to prevail over detecting new HIV infections. Modifying at-risk behaviour is difficult. Current messages for prevention must be improved.

Adult↗
PubMed1994

The evolution of a public health policy: health care providers and the transmission of HIV.

The single known instance of transmission of HIV from a health care provider to a patient raised issues concerning the responsibility of clinicians to their patients, and sparked debate over policies to prevent the spread of HIV in health care facilities. The intensity and politicization of the debate were reflected in revision of the Centers for Disease Control guidelines to control the spread of infection at health care facilities, and in legislation proposed in Congress. The guidelines and proposed legislation provoked responses by public health and medical organizations, several of which considered the measures to be unnecessarily restrictive and too costly in terms of potential benefits. This article describes the events and responses that took place during 1991-1992 after the public was made aware of the case involving transmission from provider to patient. The author examines the situation in the context of public health efforts to control the spread of HIV.

AIDS Serodiagnosis↗
PubMed2001

The evolution of Candida species and fluconazole susceptibility among oral and vaginal isolates recovered from human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

Antifungal agents can effectively treat mucosal candidiasis; however, their use can lead to colonization with less susceptible species and to resistance among normally susceptible strains. Oral and vaginal Candida isolates obtained at 3 points over 2 years from human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women were identified by species and were evaluated for in vitro fluconazole susceptibility. Prevalence of non-C. albicans strains increased over time, and these strains were more likely among women reporting current antifungal use. Among C. albicans isolates, resistance was rare, with no evidence for progressive reduction in susceptibility over time. Among non-C. albicans isolates, reduced susceptibility occurred frequently and increased with time. HIV-seropositive women were more likely to have non-C. albicans isolates with reduced susceptibility as were women reporting current antifungal use. This evolution and section of mucosa-colonizing Candida species with reduced susceptibility could play a critical early role in the development of antifungal resistance among C. albicans isolates responsible for refractory candidiasis.

AIDS-Related Opportunistic Infections↗