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At least 127 records · Page 7Linked to original sources
PubMed1999

[Virologic evolution in HIV-infected subjects with an undetectable viral load in the first trimester of 1997].

OBJECTIVES: Assess the evolution of viral load in HIV-infected patients whose viral load was < 500 copies/ml during the first three months of 1997. PATIENTS AND METHODS: The viral load during the first three months of 1998 was recorded for comparison. Data were collected from the DM12 database implanted in the CISIH and concerned 2113 patients. RESULTS: Virological failure was observed in one-third of the patients in the study cohort whose viral load was undetectable in 1997 (< 500 copies/ml) as their load was > 500 copies/ml one year later in 1998. The percentage of patients in a situation of virological failure in 1998 who were taking tritherapy in 1997 (38%) was lower than that in those who were not (47%). The clinical and immunological characteristics were however similar. The difference in the therapeutic regimen would probably explain the difference. CONCLUSION: These findings demonstrate that virological failure is an important problem. Other analyses should be conducted in other cohorts to determine the influence of non compliance or resistance to antiretroviral treatments. Future therapeutic strategies should take into account the results of such studies.

Anti-HIV Agents↗
PubMed2004

Evolution of the HIV-1 envelope glycoproteins with a disulfide bond between gp120 and gp41.

BACKGROUND: We previously described the construction of an HIV-1 envelope glycoprotein complex (Env) that is stabilized by an engineered intermolecular disulfide bond (SOS) between gp120 and gp41. The modified Env protein antigenically mimics the functional wild-type Env complex. Here, we explore the effects of the covalent gp120 - gp41 interaction on virus replication and evolution. RESULTS: An HIV-1 molecular clone containing the SOS Env gene was only minimally replication competent, suggesting that the engineered disulfide bond substantially impaired Env function. However, virus evolution occurred in cell culture infections, and it eventually always led to elimination of the intermolecular disulfide bond. In the course of these evolution studies, we identified additional and unusual second-site reversions within gp41. CONCLUSIONS: These evolution paths highlight residues that play an important role in the interaction between gp120 and gp41. Furthermore, our results suggest that a covalent gp120 - gp41 interaction is incompatible with HIV-1 Env function, probably because this impedes conformational changes that are necessary for fusion to occur, which may involve the complete dissociation of gp120 from gp41.

Amino Acid Substitution↗
PubMed1999

Adenoidal tissue mass as a clinical guide of disease evolution in vertically HIV-1 infected children.

INTRODUCTION: it is known that in early-stage HIV-induced disease there is a discrepancy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency. However, it is not known how long term progression of HIV infection is influenced by short-term changes in the adenoidal size. OBJECTIVE: To assess the reliability of adenoidal-nasopharyngeal (AN) ratio in predicting clinical evolution of pediatric HIV infection. METHODS: lateral radiographs of the nasopharynx in 94 Caucasian children born to HIV-1-infected mothers ranged from 6 months to 15 years (60 children infected with HIV-1 and 34 without HIV infection), and in a control group of 692 normal children were evaluated to obtain the AN ratio in order to identify the relationship of AN profiles with different stages of the disease. Patients were rated regarding their clinical and immunological status according to the Center for Disease Control Classification. RESULTS: statistically significant differences between the groups of HIV-1-infected children, seroreverters and controls in the AN ratio were found (P < 0.001). Moreover, significant differences were also found in individual children that correlated with clinical progression. CONCLUSION: examination of radiographic changes in adenoidal size by AN ratio in relation to clinical status during one year period in the whole group showed strong prognostic value. These findings may have important implications in the design of therapeutic strategies.

Adenoids↗
PubMedDate not supplied

[Nutritional status of patients with HIV infection. Spontaneous evolution during the hospital stay].

UNLABELLED: BASICS: Evaluate the nutritional status of HIV positive patients who are admitted to hospital for some acute process, and their evaluation, without nutritional support, during the admission. METHODS: Prospective study in HIV positive patients. Nutritional evaluation (on admission and on release); (1) anthropometric (weight, size, triceps, fold, circumference of the arm, and muscular circumference of the arm, and (2) biochemical (albumin, cholesterol, triglycerides, lymphocytes, pre-albumin, and transferrin). Statistical study: comparison of the paired means and chi squared test. RESULTS: 60 patients. Mean age 32 +/- 4.8 years, 76% men and 23% women. Staging: AIDS 84.8%, non-AIDS 15.2%. Main reason for admission: Infection (80%). Mean stay: 14 days +/- 9.5. Initial nutritional evaluation: normal: 1.7%, protein malnutrition: 5.3%, caloric malnutrition: 38.5%, mixed malnutrition: 54.3%, 85% of the patients refer weight loss. 21 patients (35%) were followed up. There were no significant differences in the anthropometric nor in the biochemical parameters, except in the levels of pre-albumin and transferrin, which improved (p < 0.001). Nutritional evaluation on release: normal: 9.5%, caloric malnutrition: 66.5%, mixed malnutrition: 23.7%. There were no cases of protein malnutrition. CONCLUSIONS: The vast majority of the HIV+ patients who are admitted, are malnourished, and after curing the acute process, 90.5% of them remain malnourished. The anthropometric measurements, albumin, cholesterol, and triglycerides do not vary during the hospital admission, despite the treatment and the clinical improvement. The increase of proteins with a short half life is due to controlling the infection, which is why these are not good parameters for the nutritional evaluation in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Origins of HIV and the evolution of resistance to AIDS.

The cross-species transmission of lentiviruses from African primates to humans has selected viral adaptations which have subsequently facilitated human-to-human transmission. HIV adapts not only by positive selection through mutation but also by recombination of segments of its genome in individuals who become multiply infected. Naturally infected nonhuman primates are relatively resistant to AIDS-like disease despite high plasma viral loads and sustained viral evolution. Further understanding of host resistance factors and the mechanisms of disease in natural primate hosts may provide insight into unexplored therapeutic avenues for the prevention of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Case fatality and health care costs in HIV-infected patients: evolution from 1992 to 2000 at Rouen University Hospital, France.

Vital prognosis in HIV-infected patients has been improved by new therapies, leading to an increase in treatment and outpatient costs but lower inpatient care costs. The aim of the study was to compare the health care costs between 1992-1996 (first half) and 1996-2000 (second half) in HIV-infected patients at Rouen University Hospital. Hospitalization costs (including inpatient and outpatient care), infectious complication treatment and antiretroviral therapy costs were evaluated from a National Health Insurance viewpoint. Between 1992 and 2000, 1212 patients were admitted at least once. Total expenditure increased between the two periods from 13,660 Euro to 27,567 Euro, i.e., a two-fold increase. During the same period, 125 deaths were avoided, and 3602 years of life were gained. The cost of one avoided death was 108,320 Euro and the cost per life-year gained was 3776 Euro.

Adolescent↗
PubMed2005

Joint modelling of bivariate longitudinal data with informative dropout and left-censoring, with application to the evolution of CD4+ cell count and HIV RNA viral load in response to treatment of HIV infection.

Several methodological issues occur in the context of the longitudinal study of HIV markers evolution. Three of them are of particular importance: (i) correlation between CD4+ T lymphocytes (CD4+) and plasma HIV RNA; (ii) left-censoring of HIV RNA due to a lower quantification limit; (iii) and potential informative dropout. We propose a likelihood inference for a parametric joint model including a bivariate linear mixed model for the two markers and a lognormal survival model for the time to drop out. We apply the model to data from patients starting antiretroviral treatment in the CASCADE collaboration where all of the three issues needed to be addressed.

Anti-HIV Agents↗
PubMed2006

HIV in pregnancy: evolution of clinical practice in the UK.

Prior to the introduction of interventions reducing mother-to-child transmission of HIV-1 natural history data reports vertical transmission rates in the order of 25%. The risk of transmission from mother-to-child has been associated with advanced maternal HIV disease, maternal plasma HIV viral load and CD4 lymphocyte count, mode of delivery, length of rupture of membranes, prematurity and breast feeding. During the last 10-15 years the introduction of prelabour cesarean section, formula feeding and antiretroviral therapy has reduced transmission to less than 1% for pregnant women in the UK who are aware of their HIV status. Attention is now turning to the minimization of possible drug side effects for both mother and infant as women are increasingly conceiving on combination antiretroviral therapy. The evolution of current UK guidelines on the prevention of mother-to-child transmission of HIV-1 are discussed.

Anti-HIV Agents↗
PubMedDate not supplied

Spontaneous release of interferon as a predictor of clinical evolution in HIV-positive subjects.

In order to establish a correlation with disease progression we prospectively evaluated ten clinical and immunologic parameters in 102 consecutive HIV-positive subjects. The eight immunologic variables were: in vitro spontaneous interferon release by peripheral blood monocytic cells, alpha- and gamma-interferon production induced by Newcastle Disease Virus and PHA, Multitest Mérieux score, PHA- and CON-A-induced lymphocyte transformation, absolute number of CD4+ cells and CD4/CD8 ratio, respectively. The two baseline clinical variables were risk factor and disease presentation. Generalized Wilcoxon analysis indicated a significant correlation of one clinical (disease presentation at entry) and three immunologic variables (spontaneous interferon release, CD4+ cell number, Multitest Mérieux) with disease progression. Baseline spontaneous release of alpha, acid-labile interferon showed the best correlation with disease progression, and appeared to be significantly associated with CD4+ cell loss. Spontaneous release of acid-labile alpha interferon by mononuclear cells in vitro could be highly predictive of disease evolution in HIV-Ab positive, AIDS-free subjects.

Evaluation Studies as Topic↗
PubMed1995

Research on disclosure of HIV status: cultural evolution finds an ally in science.

This editorial responds to Mason et al.'s (1995) "Culturally Sanctioned Secrets: Latino Men's Nondisclosure of HIV Infection to Family, Friends, and Lovers." Culture is an evolving dynamic phenomenon shaped by society, psychology, and history. Historically, familism and simpatía have been Hispanic cultural assets. As times change, however, values and behaviors that served a culture for generations may become liabilities unless they evolve to fit the changing world of the culture. In the case of Hispanic gay men, the desire to protect family members is a barrier to disclosure of HIV status. Mason et al.'s study points to areas in which cultural development is needed. Science and culture thus become allies, with science pointing the way to needed directions for adaptive cultural evolution.

Acculturation↗
PubMed2005

Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant.

BACKGROUND: Given the high prevalence of mother to child infection, the development of a better understanding of African subtype C HIV-1 transmission and natural evolution is of significant importance. In this study, we genotypically and phenotypically characterized subtype C viruses isolated over a 67-month follow-up period from an in utero-infected Zambian infant. Changes in genotype and phenotype were correlated to alterations of the host humoral immune response. RESULTS: A comparison of baseline maternal and infant samples indicated that the infant sequences are monophyletic and contain a fraction of the diversity observed in the mother. This finding suggests that selective transmission occurred from mother to child. Peaks in infant HIV-1 Env genetic diversity and divergence were noted at 48 months, but were not correlated with changes in co-receptor usage or syncytia phenotype. Phylogenetic analyses revealed an accumulation of mutations over time, as well as the reappearance of ancestral lineages. In the infant C2-V4 region of Env, neither the median number of putative N-glycosylation sites or median sequence length showed consistent increases over time. The infant possessed neutralizing antibodies at birth, but these decreased in effectiveness or quantity with time. De novo humoral responses were detected in the child after 12 months, and corresponded with an increase in Env diversity. CONCLUSION: Our study demonstrates a correlation between HIV-1 Env evolution and the humoral immune response. There was an increase in genetic diversification in the infant viral sequences after 12 months, which coincided with increases in neutralizing antibody titers. In addition, episodes of viral growth and successive immune reactions in the first 5-6 years were observed in this slow progressor infant with delayed onset of AIDS. Whether this pattern is typical of slow progressing subtype C HIV-1 infected infant needs to be further substantiated.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Genetic analysis reveals ongoing HIV type 1 evolution in infected human placental trophoblast.

To provide a better understanding of the role of placenta in vertical human immunodeficiency virus (HIV) transmission, we have studied the infection of placental trophoblast in a group of 15 mother-neonate pairs. By nested PCR amplification of the C2V3 env gene region, HIV-1 has been found to infect the placenta in five cases (33%). Phylogenetic analysis of the cloned sequences showed that all recovered maternal variants were of the B subtype. Further investigation into the ancestral relationships at the nucleotide level revealed that the trophoblast sequences evolved into a quasispecies population clearly distant from that observed in the mother. As expected, the populations transmitted to the trophoblast were also found to be more homogeneous than those in the mothers when characterized on the basis of pairwise nucleotide sequence distances. With regard to the predicted biological properties, the primary amino acid structure of the V3 loop domain was consistent, with a macrophage-tropic, non-syncytium-inducing phenotype in all patients. We also attempted to determine if any of a number of selected maternal or viral factors was associated with trophoblast infection. However, none of the followed parameters, including maternal age, disease stage, antiretroviral therapy, CCR5delta32 deletion status of the infant, and viral genotype, could be associated with viral transmission. Moreover, in one pair with proven trophoblast infection, HIV was also detected in the cord blood. Taken together, our data suggest that the productive trophoblast infection by HIV-1 in vivo is a relatively frequent event that may bear direct implications for a further transplacental propagation of the virus.

Adult↗
PubMedDate not supplied

Use of the presence of anti-protein gag antibodies as an evolution marker of HIV infection.

The paper studies the modifications occurring in the prevalence of anti-protein gag antibodies during the evolution of the infection in a paediatric population iatrogenically infected and not submitted to antiretroviral treatment. The study was performed by annual clinical examination of children and by laboratory determinations: western-blot, p24 Ag assay, determination of lymphocyte population by flowcytometry. The predictive capacity of p17 antibodies was revealed, their occurrence after seroconversion pointing to a favourable evolution, with a longer asymptomatic period; the disappearance of these antibodies during the disease indicates a more advanced stage of the disease. The disappearance of p24 and p55 antibodies during the evolution of the disease shows a more advanced stage of the disease, both clinically and as concerning the immunosuppression degree.

Biomarkers↗
PubMed2006

Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of therapy: effects on CD4+ T-cell count and HIV-1 RNA load.

Sequence analysis of HIV-1 from 440 therapy-naive individuals included within the CASCADE study, who seroconverted within 18 months of the last negative test, identified 65 persons infected with a strain carrying resistance-associated mutations. Population-based sequencing was performed for 20 of these individuals during the therapy-free follow-up period. The median time of follow-up was 15 months (interquartile range from 10 to 23 months). Of these individuals, 12 showed subsequent evolution at the resistance positions, whereas the virus of 8 people was stable during this period. In the reverse transcriptase (RT) gene, the drug-resistant 215Y or 215F codons evolved to alternative codons in all six cases, 70R reverted to the wild-type 70K in 3 of the 4 individuals, 67N evolved only in 1 of 4 patients to a wild-type 67D, 215S evolved to wild-type 215T in 1 of 3 patients, 219N evolved to 219K in 1 of 2 patients, and one patient with 184V reversed to the wild-type 184M. The 181C variant evolved to the wild-type 181Y in 1 of 2 individuals. These codon changes were caused by single nucleotide mutations. No evolution was observed for other RT mutations: 41L, 69D, 69N, 190S, 210W, 215L, 215C, 215E and 219Q. In the protease gene, resistance mutations 84V and 90M were stable in 2 individuals. Comparing the CD4+ T-cell count of the 12 evolving versus the 8 stable cases revealed no statistically significant difference at the date of the first sequence following seroconversion. Interestingly, a lower CD4+ T-cell count was observed in the group without evolution at the second sequence time point (P = 0.043). No difference in HIV-1 RNA load was observed. These results, together with the apparent pressure to mutate at the resistance-associated positions exemplify the decreased fitness of viruses carrying 21 5Y/F, 70R or 184V.

Anti-HIV Agents↗
PubMed2003

Functional evolution of the HIV-1 envelope glycoprotein 120 association site of glycoprotein 41.

Protein-protein interaction surfaces can exhibit structural plasticity, a mechanism whereby an interface adapts to mutations as binding partners coevolve. The HIV-1 envelope glycoprotein gp120-gp41 complex, which is responsible for receptor attachment and membrane fusion, represents an extreme example of a coevolving complex as up to 35% amino acid sequence divergence has been observed in these proteins among HIV-1 isolates. In this study, the function of conserved gp120 contact residues, Leu593, Trp596, Gly597, Lys601, and Trp610 within the disulfide-bonded region of gp41, was examined in envelope glycoproteins derived from diverse HIV-1 isolates. We found that the gp120-gp41 association function of the disulfide-bonded region is conserved. However, the contribution of individual residues to gp41 folding and/or stability, gp120-gp41 association, membrane fusion function, and viral entry varied from isolate to isolate. In gp120-gp41 derived from the dual-tropic isolate, HIV-189.6, the importance of Trp596 for fusion function was dependent on the chemokine receptor utilized as a fusion cofactor. Thus, the engagement of alternative chemokine receptors may evoke distinct fusion-activation signals involving the site of gp120-gp41 association. An examination of chimeric glycoproteins revealed that the isolate-specific functional contributions of particular gp120-contact residues are influenced by the sequence of gp120 hypervariable regions 1, 2, and 3. These data indicate that the gp120-gp41 association site is structurally and functionally adaptable, perhaps to maintain a functional glycoprotein complex in a setting of host selective pressures driving the rapid coevolution of gp120 and gp41.

Amino Acid Sequence↗
PubMed1993

[Cryptococcosis of the central nervous system and infection by HIV. Clinical-evolutive characteristics in 13 cases].

Cryptococcosis is the fourth cause of infection of the Central Nervous System in patients with infection by HIV. Despite this fact, the series published in our country are referred to a limited number of cases. We describe the most relevant characteristics of 13 patients with meningitis by Cryptococcus neoformans. We used as inclusion criteria a positive culture of the Cephalorhachidian Fluid (CRF). We observed a significant reduction in the levels of CD4 lymphocytes in all patients, the absence of meningitic syndrome in more than 50% cases (8/13) and a normal CRF cytobiochemistry in three patients. The thoracic radiography was normal in all cases but two, although the cryptococcus was cultured in a transbronchial biopsia of a patient with normal thoracic radiography. The Computerized Axial Tomography showed frequent alterations (5/13). Eight patients were treated with amphotericin B (0.5 mg/kg/d) and five with fluconazol (400 mg/day). Despite following a maintenance therapy with fluconazol (200 mg/d), we had two cases of recurrence in the group previously treated with fluconazol. The level of leukocytes in the CRF was the only prognosis factor (p < 0.05). Five patients died during their first hospitalization due to causes related to the infection by cryptococcus. New therapeutical guidelines are needed in order to improve the prognosis of these patients.

AIDS-Related Opportunistic Infections↗
PubMed2001

Behavioural interventions to prevent HIV infection: rapid evolution, increasing rigour, moderate success.

Behavioural interventions aim to alter behaviours that make individuals more vulnerable to becoming infected or infecting others with HIV. Research in this field has developed rapidly in recent years. Increased rigour in the design and conduct of evaluations and moderate successes in bringing about behaviour change in target populations are the key achievements so far. This paper reflects on these developments, addresses recent innovations and highlights likely areas for future work. Discussion focuses on maximising the potential effectiveness of new interventions, methodological issues relating to evaluation and implementation of interventions into practice. The paper concludes there is evidence that interventions deemed effective under evaluation conditions can be implemented in HIV prevention services and that this is the next major challenge. The immediate goal should be consolidation of the learning that has occurred, particularly efforts to maintain theoretical and evaluative rigour whilst encouraging increased collaborative partnerships between researchers, service providers and affected communities.

HIV Infections↗