[Evolution of a cohort of patients over 60 years old with HIV infection treated with highly-active antiretroviral therapy].
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Aged↗
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Results for “HIV evolution”
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[Favorable evolution of a myocardial abscess using medical treatment in an HIV-positive patient].
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Abscess↗
Histopathology of the liver in adolescents co-infected with HIV and hepatitis C virus.
Chronic hepatitis C is usually a mild disease in children; however, the evolution of children co-infected with HIV is unknown. We report the liver biopsy results of seven adolescents co-infected for over 13 years. According to the Metavir scoring system, liver specimens were classified A1-F1 in three patients and A2-F1 in four. Mild fibrosis progression is mainly explained by young age at hepatitis C virus contamination and the lack of severe immunodeficiency in the study population.
Adolescent↗
HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug treatment.
The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.
Acquired Immunodeficiency Syndrome↗
HIV-1 origins. A finger on the missing link.
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Animals↗
Autoreactivity in HIV-1 infection: the role of molecular mimicry.
Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers of autoantibodies to HLA molecules and other surface markers of CD4+ T cells appear to increase with the progression of disease and may correlate with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the immune system. Genesis of autoreactivity may be related to structural homologies of HIV-1 env-products to such functional molecules involved in the control of self-tolerance. The most impressive similarities include the HLA-DR4 and DR2, the variable regions of TCR alpha-, beta-, and gamma-chain, the Fas protein, and several functional domains of IgG and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response, through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could also include the activation of membrane-to-nucleus signal transducers resulting in increased apoptosis. The evolution of autoimmune mechanisms during HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since aspects of oligoclonal immune response to HIV-1 components may occur in several autoimmune diseases which in some instances evolve to lymphoma.
Amino Acid Sequence↗
Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children.
Highly active antiretroviral therapy (HAART) may be a contributory factor for a decreased bone mass and altered bone metabolism in HIV-infected children. However, the evolution of bone mineral density (BMD) and bone metabolism during HAART has not been studied yet. In the current longitudinal study we monitored the changes of BMD and bone metabolism over a period of 12 months. Thirty-two HIV-infected children (15 girls and 17 boys), aged from 6.3 to 17.7 yr, with a long duration of HAART exposure (40.0 months at baseline) were enrolled in the study. As a control group, 381 healthy volunteers of comparable age were assessed. BMD was measured at the lumbar spine and whole skeleton by dual-energy x-ray absorptiometry. Bone-specific alkaline phosphatase (BALP, as bone formation index) and N-terminal telopeptide of type I collagen (as bone resorption index) were measured in serum and urine, respectively. BMD values at baseline were significantly lower at all skeletal sites than those of control subjects. The annual increment of spine BMD was comparable to normal, whereas that of the whole skeleton was significantly lower (P < 0.04). BALP and N-terminal telopeptide of type I collagen concentrations were significantly higher compared with controls at baseline and at follow-up. BALP annual changes of HIV patients were significantly different from normal. Our data confirm the presence of low BMD and bone metabolism derangement in HIV-infected children treated with HAART. The role of possible therapeutic approach to restore bone mass and metabolism should be assessed in pediatrics.
Absorptiometry, Photon↗
[Vertical transmission of human immunodeficiency virus: six years of development 1987-1992)].
BACKGROUND: According to World Health Organization estimates, from the beginning of the epidemics to the end of 1994, the number of children infected by human immunodeficiency virus (HIV) was 1.5 million. This paper describes the evolution of some clinical and epidemiologic characteristics of vertically transmitted HIV infection. PATIENTS AND METHODS: All children born to HIV-infected mothers who delivered at a university hospital in Barcelona, Spain, between 1987 and 1992, were included in the study. Rates of HIV vertical transmission, HIV infection incidence and mortality due to HIV were estimated, and trends for the study period analyzed. Odds ratios were used to assess associations between variables. RESULTS: 192 newborns were identified and allocated, with respect to the year of birth, in three cohorts of 71, 58 and 63 children. Overall HIV vertical transmission rate was 16.5% and did not differ between cohorts. Infection incidence density rates increased over time (0.2, 4.9 and 8.1 cases/100 child-years, respectively; p = 0.016), while incubation periods decreased significantly (248, 103 and 114 days; p = 0.0004). There were no changes in mortality density rates (2.2 deaths/100 child-years). Regarding mothers' characteristics, a significant temporal trend (p < 0.001) for being older at delivery, belonging to the heterosexual transmission group and having symptomatic infection was observed over time. CONCLUSIONS: Certain clinical and epidemiologic aspects of HIV vertical transmission have changed over time, however the number of new cases has remained fairly constant. In our setting, both early diagnosis and clinical management of these children have improved, but primary prevention for HIV vertical transmission has not been effective. Better counselling for HIV-infected women of childbearing age is needed.
Child↗
[Management of antiretroviral treatment in HIV-infected patients exhibiting virologic failure].
THE BASES OF THERAPEUTIC FAILURE: In view of its varying clinical, immunological and virological components, therapeutic failure during HIV infection is debatable. It relies on monitoring the patient during treatment, taking into account prior therapy and the initial level of CD4 and HIV viral charge, and their evolution. Immuno-virological failure can be defined as a detectable viral charge and CD4 lymphocytes lesser than 200 elements/mm3. Therapeutic failure can be related to various factors: poor compliance to treatment, insufficient dosing, poor absorption or drug interactions reducing its efficacy and HIV resistance to antiretrovirals. THE MANAGEMENT OF PATIENTS EXHIBITING CONFIRMED THERAPEUTIC FAILURE: Requires assessment of patient's compliance and the search for drug or nutritional interactions. Pharmacological doses of antiretrovirals are useful in explaining the onset of failure or in adapting the dose. A genotype resistance test will orient the choice of new molecules in patients with reduced therapeutic options. THE CHOICE OF A NEW COMBINATION: Relies on knowledge of prior treatments and the reasons for their withdrawal (failure or intolerance) and the profile of in vitro cross-resistance to antiretrovirals. The optimal prescription combines at least two new molecules and/or a new class of antiretrovirals to which the patient has not yet been exposed. IN PATIENTS IN WHOM THERE IS NO THERAPEUTIC RESOURCES: An association of three classes of antiretrovirals with a total of 5 to 8 molecules are proposed in high-dose therapies. The use of suspension of therapy, to permit re-sensitivity, is presently being studied. THE OBJECTIVE OF TREATMENT: In non-responding patients, it is essential to retain an number of CD4 protectors depending on the clinical progression of the disease, while awaiting new therapeutic options, contrary to first or second line treatment, the priority aim of which remains reaching a undetectable viral charge.
Antiviral Agents↗
Human immunodeficiency virus type-1 episomal cDNA in semen.
BACKGROUND: Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resistant HIV-1, but studies thus far have failed to detect this marker in semen. The objectives of this study were: 1) to use a technique that maximizes DNA recovery from HIV-1 infected white blood cells in semen to determine if episomal 2-LTR cDNA is detectable in semen of ART-naïve men with other evidence of genital tract HIV-1 infection, and 2) to compare levels of HIV-1 2-LTR cDNA, RNA, and proviral DNA in semen from HIV-1+ men on ART. RESULTS: Using a somatic cell DNA extraction technique, 2-LTR cDNA was detected by PCR/ELISA in 4 out of 8 semen samples from ART-naïve men selected for other signs of seminal HIV-1 infection (positive controls). Southern blot and DNA sequencing confirmed that the amplified sequences were HIV-1 2-LTR cDNA; copy numbers ranged from 55 to 504 copies/sample. Two semen samples from a cohort of 22 HIV-1-infected men on dual nucleoside therapy, one with and one without detectable seminal HIV-1 RNA, were 2-LTR cDNA positive (336 and 8,560 copies/sample). Following addition of indinavir to the therapy regimen, no semen samples from 21 men with controlled peripheral and seminal viral loads were 2-LTR cDNA positive at 1 and 6 month time points, despite the persistence of HIV-1 proviral DNA+ semen cells and seminal cytomegalovirus (CMV) shedding in some cases. However, one individual who failed indinavir therapy and later developed distinct protease inhibitor (PI) drug resistance mutations in semen, maintained elevated levels of HIV-1 RNA and 2-LTR cDNA in semen. CONCLUSION: 2-LTR HIV-1 cDNA is detectable in semen of HIV-1-infected men. Two men on ART had 2-LTR HIV-1 cDNA in semen, suggesting that this marker may prove to be useful to monitor HIV-1 infection in the genital tract of men on ART to predict the evolution of drug resistance mutations in semen.
Journal Article↗
Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling.
The determination of protein-protein interactions and their role in diverse pathophysiological processes is a promising approach to the identification of molecules of therapeutic potential. This paper describes the identification of peptidic CCR5 receptor ligands as potential drug leads against HIV-1 infection using in vitro evolution based on phage display. A phage-displayed peptide library was used to select for anti-CCR5 peptide. Further in vitro evolution of the peptide by exon shuffling was performed to identify peptides with optimized characteristics for CCR5 receptor. This peptide inhibited HIV coreceptor activity in a cell fusion assay with an IC50 of 5 microM. It did not exhibit either agonistic or antagonistic activity on CCR5 in the concentration range used. To our knowledge, this is a first report that describes the identification of peptide ligands specific to the CCR5 receptor from a phage-displayed library and the maturation of the selected peptide sequence by gene shuffling.
Animals↗
Evaluating the cost of medications for ambulatory HIV-infected persons in association with landmark changes in antiretroviral therapy.
Costs of medications for ambulatory HIV-infected people increase as knowledge of antiretroviral therapy and therapy for opportunistic infection grows. We evaluated the evolution of drug costs for HIV-infected persons who attend a university clinic in Baltimore, Maryland. Cross-sectional abstracts of a cohort of patients for four periods, corresponding to landmark changes in therapy, who attended the clinic between June 1995 and September 1996 were obtained. Monthly medication costs for all patients were calculated. Mean costs increased significantly (p < .01) from period 1 ($447 U.S.) to period 4 ($1048 U.S.). Multivariate analysis only revealed higher costs for patients with a CD4+ count <200 cells/mm3 (p < .001). The proportion of costs attributable to antiretroviral therapy increased from 34% in period 1 to 53% in period 4. Combination therapy increased >10-fold, from 8% in period 1 to 94% in period 4. Protease inhibitor use also increased significantly, from 4% in period 2 to 53% in period 4. We quantified the increase in costs of medications from mid-1995 to late 1996. Increases in costs appear to be the result of increasing complexity of drug regimens, particularly antiretroviral therapy in combinations.
AIDS-Related Opportunistic Infections↗
Neutralization sensitivity of human immunodeficiency virus type 1 primary isolates to antibodies and CD4-based reagents is independent of coreceptor usage.
We have investigated whether the identity of the coreceptor (CCR5, CXCR4, or both) used by primary human immunodeficiency virus type 1 (HIV-1) isolates to enter CD4+ cells influences the sensitivity of these isolates to neutralization by monoclonal antibodies and CD4-based agents. Coreceptor usage was not an important determinant of neutralization titer for primary isolates in peripheral blood mononuclear cells. We also studied whether dualtropic primary isolates (able to use both CCR5 and CXCR4) were differentially sensitive to neutralization by the same antibodies when entering U87MG-CD4 cells stably expressing either CCR5 or CXCR4. Again, we found that the coreceptor used by a virus did not greatly affect its neutralization sensitivity. Similar results were obtained for CCR5- or CXCR4-expressing HOS cell lines engineered to express green fluorescent protein as a reporter of HIV-1 entry. Neutralizing antibodies are therefore unlikely to be the major selection pressure which drives the phenotypic evolution (change in coreceptor usage) of HIV-1 that can occur in vivo. In addition, the increase in neutralization sensitivity found when primary isolates adapt to growth in transformed cell lines in vitro has little to do with alterations in coreceptor usage.
Adult↗
The response in hemagglutinoinhibiting antibodies following influenza vaccination of HIV-infected children.
The study investigated the response in hemagglutinoinhibiting antibodies (HI) induced by the purified inactivated trivalent influenza vaccine prepared for the epidemic season 1996-1997, administered to a group of 24 human immunodeficiency virus (HIV)-infected children as compared to a group of HIV seronegative controls. The titres of serum HI antibodies were determined before and 30 days after vaccination. The evolution of the immune response in HIV seropositive children showed significant increases against all the antigenic components of influenza vaccine both as concerning the geometrical mean titres of HI antibodies and the protection rate (titres > or = 1:40). However, the amplitude of the immune response reported in the HIV seropositive group was lower, but insignificantly as compared to the HIV seronegative control group. No association between the individual response in HI antibodies and the determined amount of CD4' T lymphocytes was noticed.
Adolescent↗
Considerations about the prophylactic role of T cell vaccination in HIV infection.
The AIDS epidemic in Romania has properties that are both common to countries of Eastern Europe and unique to Romania. The unique aspects include the large number of cases in children infected parenterally and a relatively low but steadily increasing number of HIV infected adults. Other groups of children and adults were also exposed at risk to acquire HIV by transfusion with unscreened blood or by multiple parenteral treatments with potentially contaminated needles. Our hypothesis was that a substantial number of people in area of high endemicity was "silently" infected but did not undergo specific immune response or clinical signs. In an attempt to explore the possibility that immunization with autologous proteins (consequence of multiple transfusions) can play a role in the protection from HIV infection or in slowing down the progression of disease, we compared the incidence of autoantibodies (anti-nuclear, smooth muscle and anti-HEp-2) in a group of long survivors children with AIDS, in HIV infected children with rapid evolution and in adults at risk for parenteral acquisition of blood borne viral disease. We analyzed also the incidence of some blood borne viral infections and the presence of anti-HLA antibodies in the same groups of patients. Our results do not support the suggestion that HIV infection or AIDS can be prevented, respectively, delayed by T-cell vaccination.
Adolescent↗
[Primary cavity-based lymphoma and HIV infection].
BACKGROUND: Primary cavity-based lymphomas (PCBL) represent and uncommon group on non-Hodgkin lymphomas associated with AIDS. They present as malignant effusions with no bone marrow or lymph node involvement, although some cases with bone marrow infiltration at advanced stages have been reported. Tumoral cells are monoclonal and are occasionally infected with human herpesvirus type-8 (HHV-8). PATIENTS AND METHODS: The clinical and evolutive characteristics of six HIV-positive patients with PCBL were analysed. In three of them the presence of genetic sequences of HHV-8 in peripheral blood lymphocytes and lymphomatous effusions was investigated by PCR. RESULTS: The mean age of patients was 37 years and 5 were males. The only female patient had been drug abuser, four males were homosexuals and the other promiscuous heterosexual. The mean CD4+ lymphocyte count was 84 x 10(6)/l (range: 20-180) and all of them had been diagnosed of AIDS. The presentation forms were as pericardial effusion in one case, pleural effusion in three and tumoral ascites in two. Two of the male patients had also Kaposi sarcoma (KS). At diagnosis none of them had infiltration of the bone marrow nor lymphadenopathy. Most malignant cells had immunoblastic traits. The effusions had the characteristics of an exudate and the mean value of lactate dehydrogenase (LDH) was 5,255 IU/l (range: 1,500-11,483). In the three cases investigated there was HHV-8 DNA in the lymphocytes present in the lymphomatous effusion and in peripheral blood. The mean survival after diagnosis was 89 days (7-240). The female patient died without therapy seven days after admission and the five male patients were treated with chemotherapy with a poor response. CONCLUSIONS: HIV-related PCBL associated or not with KA appear in severely immunodepressed patients, their behaviour is very aggressive and its clinical course fatal in a short period of time. The are often associated with KS and HHV-8 seems to be the involved causative agent.
AIDS-Related Opportunistic Infections↗
Absence of seroreversion in 80 HAART-treated HIV-1 seropositive patients with at least five-years undetectable plasma HIV-1 viral load.
Partial or complete seroreversion for HIV-1, or incomplete antibody evolution are relatively rare events that have so far only been described in patients treated with HAART early after virus infection. Whether seroreversion is seen in patients treated effectively with HAART years after their acute infection has not been investigated so far. Therefore we have investigated anti-HIV antibody levels in 80 patients treated with HAART during chronic HIV-1 infection, who had an undetectable HIV-1 plasma viral load for at least five years. In none of the patients we observed seroreversion, and there was also no significant decrease or increase in antibody levels in this group of patients. So, successful HAART treatment during chronic HIV-1 infection does not induce seroreversion.
Journal Article↗
[Cost-effectiveness of initial adherence to antiretroviral therapy among HIV infected patients in Belo Horizonte, Brazil].
BACKGROUND: In Brazil, there is free antiretroviral (ARV) distribution to patients with HIV disease by the National Health System. Adherence to the treatment is one of the main factors that health services can manage to increase the effectiveness of the ARV medication. The aim of this study is to evaluate the cost-effectiveness of initial adherence to the ARV therapy and to identify factors that influence patient's costs and global evolution. METHODS: Prospective study of HIV infected patients receiving their first ARV prescription in two public referral centers to HIV/Aids, Brazil. The non-adherence was defined as the intake of <95% of the prescribed doses for 3 days prior to the first follow-up visit. A cost-effectiveness ratio was calculated for either groups, the adherent and the non-adherent. Univariate and multivariate analysis were performed using multiple linear and binary logistic regression models. RESULTS: 79.7% of the 197 participants was adherent to the ARV treatment and the ratio cost-effectiveness obtained for this group (2667.67 Eros) was smaller than the ratio observed among the non-adherent group. Multivariate analysis (p < 0.05) showed that adherence to ARV therapy and use of protease inhibitors in the treatment were associated with higher direct cost of care. The favorable global evolution was associated with being asymptomatic, TCD4+ linphocyte count >200 cels/mm3 and be adherent to the ARV treatment. CONCLUSIONS: The observed results supported the ARV therapy as a cost-effective intervention. However, low adherence increases the risk of therapeutic failure and illness progression that results in a negative impact on the cost-efectiveness of the ARV therapy.
Adult↗