Publications (26)102.38 Total impact
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Article: Rate and predictors of non-AIDS events in a cohort of HIV-infected patients with a CD4 T cell count above 500 cells/mm3.
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ABSTRACT: Background: The reduction of risk of non-AIDS events after antiretroviral therapy (cART) initiation and the crude incidence rate (CIR) of these events in patients who control the viral load without cART (controllers) in a cohort of 574 antiretroviral naïve patients with a baseline CD4 T cell count above 500 cells/mm3 were assessed. Methods: Non-AIDS severe events were defined as a first admission to the hospital due to non-AIDS-defining malignancies, cardiovascular, neuropsychiatric, liver-related or end-stage renal disease events. Potential determinants of non-AIDS/death events were studied using Cox regression models. Results: Eighty-five non-AIDS/death events occurred during 6062 persons-years of follow-up with a CIR of 1.4 per-100-PYFU. Factors associated with non-AIDS/death event were age (HR 3.4; 95%CI:1.6-6.9), nadir CD4 below 350 cells/mm3 (HR 2.5; 95%CI:1.4-4.6) and a last determination of viral load above the median (HR 1.9; 95%CI:1.0-3.3). The CIR of non-AIDS/death events was 2.1 and 1.8 per-100-PYFU before and after cART in patients who started cART (n=446). A reduction of CIR of non-AIDS events after cART initiation was only observed in patients with a nadir of CD4 above 350 cells/mm3 (2.5 vs 0.6 per-100-PYFU P= 0.004 and remained stable after cART in patients with a median nadir of CD4 below 350 cells/mm3. CIR was similar in elite, viremic and non controllers (1.1, 1.0 and 1.5 per-100-PYFU, respectively, P=0.25). Conclusions: Reduction of CIR of non-AIDS events after cART initiation depends on nadir CD4 T cell count. Most of the controllers patients had a CIR similar to non-controllers. These data support the early initiation of cART in HIV infected patients.AIDS research and human retroviruses 03/2013; · 2.18 Impact Factor -
Article: INFLUENCE OF EPISODES OF INTERMITTENT VIREMIA ("BLIPS") ON IMMUNE RESPONSES AND VIRAL LOAD REBOUND IN SUCCESSFULLY TREATED HIV-INFECTED PATIENTS.
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ABSTRACT: Background: Presenting episodes of intermittent viremia (EIV) under cART is frequent, but there exists some controversy about their consequences. They have been described to induce changes in immune responses potentially associated to a better control of HIV infection. Conversely, it has been suggested that EIV increase the risk of virological failure. Methods: A retrospective analysis of a prospective, randomized double blinded placebo-controlled study was performed. Twenty-six successfully treated HIV-infected adults were randomized to receive an immunization schedule or placebo, and after one year of follow-up cART was discontinued. Influence of EIV on T-cell subsets, HIV-1 specific T-cell immune responses, viral load rebound and the risk of developing genotypic mutations were evaluated, taking into account the immunization received. Results: Patients with EIV above 200 copies/mL under cART had a lower proportion of CD4+, CD4+CD45RA+RO- T-cells, a higher proportion of CD8+ and CD4+CD38+HLADR+ T-cells and higher HIV specific CD8+ T-cell responses compared to persistently undetectable patients. After cART interruption, patients with EIV presented a significantly higher viral rebound (p = 0.007), associated with higher increases in HIV specific lymphoproliferative responses and T-cell populations with activation markers. When patients with EIV between 20-200 copies/mL were included, most of the differences disappeared. Conclusion: Patients who present EIV above 200 copies/ml showed a lower CD4+ T-cell count and higher activation markers under cART. After treatment interruption, they showed higher specific immune responses against HIV that did not prevent a higher virologic rebound. EIV between 20 and 200 copies/ml did not have this deleterious effect.AIDS research and human retroviruses 11/2012; · 2.18 Impact Factor -
Article: Reasons for not participating in a phase 1 preventive HIV vaccine study in a resource-rich country.
AIDS patient care and STDs 06/2012; 26(7):379-82. · 2.68 Impact Factor -
Article: The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses.
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ABSTRACT: Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses.Immunology 07/2011; 133(3):318-28. · 3.32 Impact Factor -
Article: Evaluation of the Roche COBAS® TaqMan® HIV-1 test for quantifying HIV-1 RNA in infected cells and lymphoid tissue.
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ABSTRACT: Lymphoid tissue is the main reservoir of HIV-1 in infected individuals. In this study the COBAS® TaqMan® HIV-1 test was evaluated for use with the High Pure System (HPS), for quantifying HIV-1 RNA in infected cells and lymphoid tissue specimens. Serial dilutions of 8E5-LAV1 infected T-cells into SUP-T1 cells and 44 tonsil specimens were examined. Some modifications of the test were required, such as the removal of residual DNA and the HIV-1 RNA output copies were adjusted to the sample input and expressed as HIV-1 RNA copies/μg of total RNA. The Roche COBAS® TaqMan HIV-1® (HPS) test proved to be a robust, sensitive, specific and reproducible method for quantifying HIV-1 RNA in infected cells and lymphoid tissue. Linearity and reproducibility were observed in serial dilutions of 8E5-LAV1 infected T-cells (R²>0.86). High reproducibility was found in clinical tonsil specimens (Wilcoxon test p > 0.05). rDNase I treatment was essential to avoid false positives caused by residual HIV-1 DNA, mainly in tonsil specimens obtained from infected patients receiving effective antiretroviral treatment. Probit analysis determined the limit of detection as 22HIV-1 RNA copies/μg of total RNA. The Roche COBAS® TaqMan® HIV-1 (HPS) test thereby proved to be a helpful tool for measuring the HIV-1 viral load in infected cells and lymphoid tissue reservoirs.Journal of virological methods 03/2011; 174(1-2):69-76. · 2.13 Impact Factor -
Article: Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells.
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ABSTRACT: By interacting with CD26 on the CD4+ T cell surface and with the AdoR A(₂B) on the DC surface, ADA triggers a costimulatory signal for human T cells. The aim of this study was to know whether ADA-mediated costimulation plays a role in the differentiation of T cells. The results show that irrespective of its enzymatic activity and dependent on TNF-α, IFN-γ, and IL-6 action, ADA enhanced the differentiation of CD4+CD45RA+CD45RO⁻ naïve T cells toward CD4+CD25+CD45RO+ Teffs and CD4+CD45RA⁻CD45RO+ memory T cells. Furthermore, ADA potentiated generation of CD4+CD25(high)Foxp3+ Tregs by a mechanism that seems to be mainly dependent on the enzymatic activity of ADA. Interestingly, an ADA-mediated increase on Teff, memory T cell, and Treg generation occurred, not only in cocultures from healthy individuals but also from HIV-infected patients. These data suggest that ADA is a relevant modulator of CD4+ T cell differentiation, even in cells from immunologically compromised individuals.Journal of leukocyte biology 10/2010; 89(1):127-36. · 4.99 Impact Factor -
Article: Immunological dysfunction in HIV-1-infected individuals caused by impairment of adenosine deaminase-induced costimulation of T-cell activation.
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ABSTRACT: The cell surface association between CD26 and adenosine deaminase (ADA) has a costimulatory function during T-cell activation. Several studies have revealed correlations among CD4(+) CD26(+) T-cell depletion, increased serum levels of ADA, and the evolution of human immunodeficiency virus (HIV) infection, implicating CD26 and ADA in HIV disease progression. In this context, we aimed to determine whether ADA costimulation could be altered during HIV infection. ADA costimulation was investigated in cells from HIV-infected patients (n = 36) in terms of proliferation and cytokine secretion. An effect of ADA on T-cell proliferation was found in HIV-1-infected patients and correlated positively with the CD4(+) percentage and the nadir CD4 count and negatively with viral load, demonstrating that the response depends on the immunological status of the patient. The robust ADA-induced increase in cytokine production [interferon (IFN)-gamma, interleukin (IL)-6 and IL-10] was markedly reduced in T cells from HIV-1-infected subjects. To eliminate some of the variables associated with immunological defects in HIV-1-infected patients, anti-CD3 plus ADA assays with T cells from healthy volunteers were performed in the presence of recombinant glycoprotein 120 (gp120). It was found that gp120 was responsible for the impairment of the ADA-CD26 interaction and consequently of the ADA-induced effect on both costimulation and cytokine production. The gp120-mediated disruption of the CD26-ADA interaction is a novel mechanism that might explain, at least in part, the altered immunological features observed in HIV-1-infected patients and may have significant relevance in AIDS pathogenesis.Immunology 11/2009; 128(3):393-404. · 3.32 Impact Factor -
Article: Adenosine deaminase enhances T-cell response elicited by dendritic cells loaded with inactivated HIV.
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ABSTRACT: As host immunological defenses are impaired during HIV infection, it is difficult to elicit good responses when attempting to develop therapeutic vaccines against HIV. To try to solve this situation, adjuvants, particularly cytokines, are currently under evaluation. Owing to the fact that adenosine deaminase (ADA) is a member of the family of growth factor with deaminase activity, we tested whether it could improve immune responses in the development of HIV dendritic-cell-based therapeutic vaccines. A co-culture model approach has been used to test the usefulness of ADA as adjuvant. Monocyte-derived dendritic cells from HIV-infected patients were pulsed with inactivated HIV, matured and co-cultured with autologous T cells. Addition of ADA to the co-cultures resulted in enhanced CD4(+) and CD8(+) T-cell proliferation and robust ADA-induced increase in cytokine production (IFN-gamma, TNF-alpha and IL-6). As IFN-gamma, TNF-alpha and IL-6 promote the Th1 versus Th2 phenotype and improve T helper proliferation responses and antigen-specific CTL responses ADA may be considered a promising candidate for therapeutic vaccine adjuvant.Immunology and Cell Biology 09/2009; 87(8):634-9. · 3.66 Impact Factor -
Article: Short Communication: Natural killer cells and expression of KIR receptors in chronic HIV type 1-infected patients after different strategies of structured therapy interruption.
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ABSTRACT: Few data evaluating the NK cell profile during structured therapy interruption (STI) in chronic HIV-1 infection are available. Changes in NK cell percentages and KIR and NKG2A receptors were analyzed at baseline and after 2 years of follow-up in 121 patients on ART with CD4(+) >450 cells/ml and VL <200 copies/ml randomized in three arms according to the criteria employed to resume ART during STI: virological arm (VA n = 47, VL >30,000 copies/ml or CD4 <350 cells/ml), immunological arm (IA n = 37, CD4< 350 cells/ml), and a control arm (n = 37) in which ART was maintained. After 2 years of follow-up, a decrease in CD3(-)CD56(+) CD16(+) cell percentages in VA and IA patients, but not in CA patients, was observed. Those patients with higher decrease in CD3(-)CD56(+)CD16(+) cells had a higher decrease in CD4(+) cells (r = 0.35, p = 0.001) and higher increase in PVL (r = -0.26, p = 0.02). KIR and NKG2A receptor expression tended to increase in CA and decreased in the other two arms (more in IA than in VA). Patients who displayed a greater decrease in CD4(+) T cells and a greater rise in PVL after 2 years of follow-up had a significantly higher decrease in KIR and NKG2A receptors expressed in CD3(-)CD56(+) cells. Patients who presented the lowest levels of total NK cells and KIR and NKG2A receptor expression after STI showed the poorest virology or immunology outcomes. This finding suggests that STI could decrease the number of NK subsets, which is related to the worst clinical development in these patients.AIDS research and human retroviruses 12/2008; 24(12):1485-95. · 2.18 Impact Factor -
Article: Influence of repeated cycles of structured therapy interruption on the rate of recovery of CD4+ T cells after highly active antiretroviral therapy resumption.
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ABSTRACT: CD4+ T cell recovery dynamics were analysed during the 'on treatment' periods in structured therapy interruption (STI) as well as the long-term immune reconstitution with highly active antiretroviral therapy (HAART) after finishing STI. One hundred and twenty HIV-1-infected patients on successful HAART were randomized to receive for 2 years continuous HAART (n=37) or two different strategies of STI (n=83). After this period, most patients received continuous HAART for 2 years. During the STI period, the rate of recovery of CD4+ T cells decreased progressively from the first to the last resumption of HAART {median change of increase: +232 [interquartile range (IQR): +126, +318], +116 (IQR: +10, +471), +87 (IQR: -54, +252) and -26 (IQR: -352, +211) cells/mm3 after the first, second, third and fourth resumption, respectively}. After the STI period and 2 years of continuous HAART, the median CD4+ count remained significantly lower than at baseline in STI arms, both in the virological arm [559 (IQR: 383, 727) versus 771 (IQR: 625, 913) cells/mm3, P<0.0001] and the immunological arm [619 (IQR: 501, 789) versus 787 (IQR: 657, 954) cells/mm3, P<0.0001], but not in the control arm [886 (IQR: 564, 1122) versus 780 (IQR: 539, 945) cells/mm3, P=0.68]. In a multivariate analysis, the nadir of CD4+ T cells and the baseline value of CD4+ before the STI period independently predicted the level of CD4+ T cells 2 years after resumption of HAART (in both cases, P<0.0001). The drop in CD4+ cell count after a first and a second period of 3 months of interruption of HAART was completely recovered after resuming HAART; conversely, interruptions longer than 6 months were deleterious for the recovery of CD4+. CD4+ cell count did not rebound completely in patients who received 2 years of HAART after 2 years of STIs.Journal of Antimicrobial Chemotherapy 11/2008; 63(1):184-8. · 5.07 Impact Factor -
Article: Redistribution of FOXP3-positive regulatory T cells from lymphoid tissues to peripheral blood in HIV-infected patients.
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ABSTRACT: Regulatory T (Treg) cells are altered during HIV replication, but their role in chronic infection is controversial and lacks reproducibility between series. FOXP3 is a specific marker of Treg cells. We study for the first time FOXP3 expression in a unique series of paired samples at different time points of HIV infection. Design: Paired samples from lymphoid tissue and peripheral blood were simultaneously obtained from 27 HIV-infected patients (before and after highly active antiretroviral therapy [HAART]) and 6 controls. We analyzed FOXP3 expression by TaqMan (Universal PCR Master Mix; Applied Biosystems, Foster City, CA) reverse transcriptase polymerase chain reaction in lymphoid tissue and peripheral blood. Treg cells were assessed in lymphoid tissue by immunohistochemistry/computer image analysis and in peripheral blood by flow cytometry. CD4 cell counts and viral loads were obtained. HIV-infected patients had a low FOXP3 copy number and Treg cell frequencies in lymphoid tissue but a high number of Treg cells in peripheral blood. Lymphoid tissue FOXP3 expression decreased after HAART, and it correlated to lymphoid tissue viral load. Patients treated with nonnucleoside HAART had the lowest lymphoid tissue FOXP3 expression. HIV-infected patients had low FOXP3 expression in lymphoid tissue and redistributed Treg to peripheral blood. HAART reduced even more the proportion of lymphoid tissue Treg in association with the immunologic recovery observed after treatment. The type of HAART may have an impact on the distribution of Treg cells.JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2008; 46(5):529-37. · 4.43 Impact Factor -
Article: Polymorphisms in the 3' untranslated region of the fractalkine (CX3CL1) gene and the risk of HIV-1 infection and disease progression.
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ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.AIDS 05/2007; 21(7):891-3. · 6.24 Impact Factor -
Article: Effect of genetic variants of CCR2 and CCL2 on the natural history of HIV-1 infection: CCL2-2518GG is overrepresented in a cohort of Spanish HIV-1-infected subjects.
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ABSTRACT: Polymorphisms in the genes that encode for the CCR2 chemokine receptor and its natural ligand CCL2 have been shown to influence the natural history of HIV-1 infection, although data are inconsistent. Our aim was to determine whether functionally active CCR2 and CCL2 genetic variants influence the risk of infection and disease progression in a cohort of white Spaniards. This was a multicenter genetic association case-control study. Two single nucleotide polymorphisms (SNPs), V64I (G > A) of the CCR2 gene and -2518 (A > G) of the CCL2 gene, were assessed in 318 individuals: 73 HIV-1-infected long-term nonprogressors (LTNPs) of >16 years duration, 109 HIV-1-infected usual progressors (UPs), 36 heavily exposed to HIV-1 but uninfected individuals (EUs), and 100 control subjects. The distribution of the CCR5Delta32 allele was also assessed. Genotyping was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) or PCR and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared by the chi2 test and the Fisher exact test. CCR2 genotype distribution and allele frequencies showed nonsignificant differences between groups. The distribution of CCL2 alleles showed no significant differences between groups. HIV-1-infected individuals had, however, a significantly higher prevalence of the variant homozygous CCL2 GG genotype compared with EUs (P = 0.02). This result persisted when we studied only individuals with wild-type CCR5. Genotype and allele distribution of CCL2 was similar in HIV-1-infected UPs and LTNPs. In our cohort of white Spaniards, homozygosity for the variant CCL2-2518GG genotype is overrepresented in HIV-1-infected subjects.JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2007; 44(2):132-8. · 4.43 Impact Factor -
Article: HIV and syphilis: when to perform a lumbar puncture.
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ABSTRACT: The objectives of this study were to determine predictive factors for neurosyphilis in HIV-infected patients with syphilis and optimize the use of lumbar puncture. The authors reviewed 112 cases of HIV-infected patients with syphilis who underwent a lumbar puncture. Diagnosis of neurosyphilis was based on a cerebrospinal fluid white blood cells count > or =20/microL, and/or a reactive cerebrospinal fluid-Venereal Disease Research Laboratory, and/or a positive intrathecal T. pallidum antibody (ITPA) index. Twenty-six of 112 had neurosyphilis. Neurologic manifestations and serum rapid plasma reagin (RPR) were associated with neurosyphilis (P = 0.036, P = 0.018, respectively). In multivariate analysis, log(2)RPR was still associated with neurosyphilis (P = 0.005). In patients without neurologic manifestations, the risk of neurosyphilis increases gradually with log(2)RPR. A serum RPR of 1/32 seems to be the best cutoff point to decide the performance or not of a lumbar puncture (sensitivity 100%, specificity 40%). In HIV-infected patients with syphilis, lumbar puncture could be restricted to those with neurologic manifestations or a serum RPR > or =1/32.Sex Transm Dis 03/2007; 34(3):141-4. · 2.87 Impact Factor -
Article: An integral care telemedicine system for HIV/AIDS patients.
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ABSTRACT: In this article we will describe a new approach to improve the quality of care of chronic HIV/AIDS patients, combining the integral care approach with a telemedicine system. Following the integral care approach, we included the patient in a multidisciplinary care team, covering the whole process of care with a telemedicine system that allows the patient to improve his/her self-care and to be remotely followed-up by the healthcare professionals. This challenge has been met by the creation of the "VIHrtual Hospital" project. Its main goal is the definition, development, clinical routine installation and evaluation of a telemedicine service that complements standard care with a telecare follow-up for treating stable HIV infected patients, in a chronic stage of their disease, and study if that improves the quality of assistance and the expense per patient compared to the conventional control (without telemedicine service) that patients usually have. Although the study is not yet finished, in the discussion the main benefits and drawbacks of this telemedicine system are described. The main conclusion of the article is that a new home telecare model for chronic HIV/AIDS patients has been created and has been implemented through the "VIHrtual Hospital" in the Clinic Hospital in Barcelona (Spain). The architecture of this web-based system fulfills the demanding security and integration requirements of the IT department of the hospital. An easy-to-use graphical interface for both patients and professionals has also been developed. The low costs of the system allow us to cover a wide range of patients and promising results are being obtained regarding the use of telemedicine systems for improving the follow-up care of chronic HIV/AIDS patients and for creating a new care model for this disease.International Journal of Medical Informatics 10/2006; 75(9):638-42. · 2.41 Impact Factor -
Article: Dynamics of T cells subsets and lymphoproliferative responses during structured treatment interruption cycles and after definitive interruption of HAART in early chronic HIV type-1-infected patients.
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ABSTRACT: Little is known about the consequences of short cycles of structured treatment interruption or definitive interruption of HAART for both T cell subset dynamics and T lymphoproliferative responses (LPR). Immunological follow-up was performed in 45 early chronical HIV-1-infected patients during short STI cycles during the first 12 weeks after the definitive interruption of HAART (DTI) and, thereafter, until VL reached a plateau. During STI cycles, CD8(+), CD8(+), CD28(+), activation markers and naive CD4(+) T cells increased significantly (p < 0.0001), while both naive CD8(+) and memory CD4(+) T cells decreased. During DTI, CD8(+) CD28(+) T cells fell and CD4(+) naive T cells stabilized and the rest of the T cell subsets presented changes similar to those during STI cycles. Despite a transient increase in LPR to recall antigens and HIV proteins during STI cycles, LPR to polyclonal stimuli and pathogens decreased over the study. Differences in T cell subset dynamics and LPR observed throughout the study suggest that multiple exposures to low levels of antigen could improve the immune system, mainly by driving T cell maturation. Conversely, higher and longer viral replication after cessation of HAART overwhelms the immune system. These data may help to guide future immune-based therapies.AIDS Research and Human Retroviruses 07/2006; 22(7):657-66. · 2.25 Impact Factor -
Article: Transmission of hepatitis C virus by discarded-needle injury.
Clinical Infectious Diseases 08/2005; 41(1):129-30. · 9.15 Impact Factor -
Article: A Home Integral Telecare System for HIV/AIDS Patients.
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ABSTRACT: VIHrtual Hospital is a telemedicine web system for improving home integral care of chronic HIV patients through the Internet. Using the videoconference, chat or messaging tools included in the system, patients can visit their healthcare providers (physician, psychologist, nurse, psychiatrist, pharmacist, and social worker), having these access to the Electronic Patient Record. The system also provides a telepharmacy service that controls treatment adherence and side effects, sending the medication to the patient's home by courier. A virtual community has been created, facilitating communication between patients and improving the collaboration between professionals, creating a care plan for each patient. As a complement, there is a virtual library where users can find validated HIV/AIDS information helping to enhance prevention. This system has been developed using low cost technologies in order to extend the number of patients involved in its trial. Thus, VIHrtual Hospital is now on trial in the Hospital Clinic (Barcelona, Spain) involving a hundred patients and twenty healthcare professionals during two years.Although we are still waiting for the final results of the trial, we can already say that the use of telemedicine systems developed ad hoc for a chronic disease, like HIV/AIDS, improve the quality of care of the patients and their care team. The system described is a good example of the possibilities that technologies are offering to create new chronic patient care models based on telemedicine.Studies in health technology and informatics 02/2005; 114:23-9. -
Article: Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence.
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ABSTRACT: Plasma viral load and T-cell subset determinations in blood are the markers used for monitoring HIV-1 infection. However, key pathogenesis events, viral replication and most immunologic changes occur in the lymphoid tissues. We have studied the tonsillar biopsies of 30 patients in the early stages of the disease, before initiating treatment and after 12 and 36 months of fully effective highly active antiretroviral therapy. We have investigated the HIV RNA by polymerase chain reaction (lymphoid tissue viral load), the immunohistochemical HIV-p24 antigen expression, as well as the lymphoid tissue architecture and lymphoid cell subsets using morphometry. The lymphoid tissue viral load and the immunoexpression of p24, which was found to be mainly associated with follicular dendritic cells, decreased significantly after treatment, but did not disappear in all cases, even after 36 months of treatment. A significant improvement of the lymphoid tissue architecture was also observed after treatment, with recovery of follicular structures. These histological changes correlated with the lymphoid tissue viral load. Moreover, the counts of CD4+ increased whereas CD8+ and cytotoxic lymphocytes (CD8+ granzyme B+) decreased significantly, the latter in both interfollicular and intrafollicular areas. However, these cellular counts after treatment did not reach those of lymphoid tissue of non-HIV-infected patients used as control cases. Naive (CD45RA+) and memory (CD45RO+) cells also improved significantly after treatment. In conclusion, in HIV-infection the impact of treatment can only be assessed completely in the lymphoid tissue reservoir, where most of the virus is stored and associated with follicular dendritic cells. Highly active antiretroviral therapy produces a significant recovery of lymphoid tissue architecture and lymphoid cell subsets, which are associated with the decrease of lymphoid tissue viral load. However, these parameters studied in lymphoid tissue are not re-established completely, even after 36 months of highly active antiretroviral therapy.Modern Pathology 02/2005; 18(1):127-36. · 4.79 Impact Factor -
Article: Similar HIV-1 evolution and immunological responses at 10 years despite several therapeutic strategies and host HLA Types.
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ABSTRACT: Two sexual partners infected with related HIV-1 viruses and enrolled in different therapeutic strategies including structured treatment interruptions (STI) provided us an opportunity to compare long term (10 years) viral genetic evolution for closely related isolates in different hosts. HLA loci were molecularly typed and different genetic markers were studied. The viral genetic evolution was studied by sequencing pol and env genes. The HIV-specific CD4+ and CD8+ T cell responses were assessed by the lymphoproliferative response (LPR) and an ELISPOT assay, respectively. HLA class I loci of patients A and B were different and both of them were heterozygous for CCR5delta32 gene. During the two STI studies, viral load of both patients rebounded after treatment interruption and both developed a transitory strong helper and CTL responses. After definitive interruption of therapy, viral load remained below 5,000 copies/ml without therapy during the two years of follow-up. Two patients infected with related viruses showed a similar dynamics of viral evolution and CD4 T cells, despite hosts having a different HLA type and being treated with several therapeutic protocols, after 10 years of infection. These results suggest that, in this case, an effective immunological response to STI depended more on the virus than on the characteristics of the host.Journal of Medical Virology 09/2004; 73(4):495-501. · 2.82 Impact Factor
Top co-authors
Top Journals
Institutions
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2008–2013
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Hospital Clínic de Barcelona
Barcelona, Catalonia, Spain
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2002–2010
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University of Barcelona
- Departamento de Bioquímica y Biología Molecular
Barcelona, Catalonia, Spain
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