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Del Romero J.,Centro Sanitario Sandoval | Castilla J.,CIBER ISCIII | Hernando V.,CIBER ISCIII | Rodriguez C.,Centro Sanitario Sandoval | Garca S.,Centro Sanitario Sandoval
BMJ (Online) | Year: 2010

Objective: To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment. Design: Cross sectional and prospective cohort studies. Setting: HIV clinic in Madrid, Spain. Participants: Stable heterosexual couples with one partner with HIV-1 infection (index partner) and the other reporting this sexual relationship as the only risk exposure. Main outcome measures: HIV seroprevalence in non-index partners at enrolment and seroconversions in follow-up according to antiretroviral treatment taken by the index partner. Results: In 476 couples in which the index partner was not taking antiretroviral treatment, HIV seroprevalence at enrolment in non-index partners was 9.2% (n=44), whereas in 149 couples in which the index partner was taking combined antiretroviral therapy no partner was infected (P<0.001). During follow-up, the 341 serodiscordant couples in which the index partner was not taking antiretroviral treatment had about 11 000 acts of intercourse without condoms, 50 natural pregnancies, and five HIV seroconversions (0.0004 per unprotected intercourse; 95% confidence interval 0.0001 to 0.0010); 294 of these couples always used condoms, accounting for about 42 000 acts of intercourse, 136 risk exposures from condom failure, and one HIV seroconversion. The relative risk associated with condom use was 0.07 (0.01 to 0.58). In 144 couples the index partner was taking combined antiretroviral treatment; they accounted for over 7000 unprotected acts of intercourse and 47 natural pregnancies but no HIV seroconversion (0 to 0.0005 per unprotected intercourse). Conclusions: The heterosexual infectivity of HIV-1 in individuals taking effective antiretroviral treatment is low. Avoidance of unprotected intercourse and receipt of antiretroviral treatment by the infected partner in accordance with protocols are complementary measures to prevent HIV transmission.


Sierra-Enguita R.,Hospital Carlos III | Rodriguez C.,Centro Sanitario Sandoval | Aguilera A.,Hospital Conxo CHUS | Gutierrez F.,University Miguel Hernández | And 8 more authors.
AIDS | Year: 2014

Background: Transmission of HIV-1 with drug resistance mutations (DRMs) in Spain remains stable around 13%. However, the profile of recent HIV-1 seroconverters has experienced significant changes. Methods: Retrospective analyses of all individuals with HIV-1 infection acquired within the past 12 months recruited at a national registry since year 1997. Results: A total of 1032 recent HIV-1 seroconverters were examined (92.2% men; median age 31 years; 84% homosexual men). At the moment of diagnosis, median plasma HIV-RNA and CD4+ cell counts were 4.5 log copies/ml and 558 cells/ml, respectively. A total of 136 individuals (13.8%) carried non-B subtypes. Major primary DRMs were found in 13.4%, being 7.7% for nucleoside reverse transcriptase inhibitor (NRTI), 5.8% for nonnucleoside reverse transcriptase inhibitor (NNRTI) and 2.9% for protease inhibitor. NRTIDRMsignificantly declined from 23.7% in 1997-2000 to 5.7% in 2010-2012 (P<0.01). Overall, X4 viruses were found in 19.7% of HIV-1 seroconverters, increasing from 11.5% before 2001 to 23.3% since year 2010 (P=0.04). Interestingly, median CD4+ cell counts were significantly lower in seroconverters diagnosed during the last period after adjusting for potential confounders. In multivariate analyses, X4 tropism, high HIV-RNA, foreigners and non-B subtypes were independent predictors of lower CD4+ cell counts. Conclusion: Transmission of NRTI DRM has declined significantly in recent HIV-1 seroconverters in Spain. Conversely, X4 tropic viruses are on the rise and currently account for 23.3% of new HIV-1 infections. These individuals present with lower CD4+ cell counts suggesting that circulating HIV-1 strains might have gained virulence. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Plaza Z.,Hospital Carlos III | Aguilera A.,Hospital Conxo CHUS | Mena A.,Inibic Complexo Hospitalario Universitario | Vispo E.,Hospital Carlos III | And 9 more authors.
AIDS | Year: 2013

Background: HIV worsens the natural history of chronic hepatitis B virus (HBV) infection. Suppression of HBV replication slows progression of liver damage. Information about the influence of HIV on response to tenofovir in HIV/HBV-coinfected patients is scarce. Methods: All individuals with persistent HBsAg+ at four clinics in Spain were identified. Information from the subset that initiated tenofovir therapy was examined. Results: A total of 176 patients with chronic hepatitis B were evaluated, of whom 138 (78.4%) were coinfected with HIV. Prior lamivudine exposure was extensive in both groups, and nearly half of HBV viremic patients harboured drug resistance mutations. Most patients took tenofovir coformulated along with emtricitabine (Truvada). Of 101 HBV viremic patients at the time of beginning tenofovir (78 with HIV coinfection and 33 with HBV alone), a similar proportion achieved undetectable HBV-DNA at weeks 24, 48 and 96 of tenofovir therapy. Interestingly, HIV/HBV-coinfected patients with positive HBeAg showed a lower response than HBeAg-negatives. In multivariate analysis, however, baseline serum HBV-DNA was the only predictor of virological response to tenofovir. Conclusion: The antiviral efficacy of tenofovir is similar in HIV/HBV-coinfected and HBV-monoinfected patients, achieving undetectable HBV-DNA nearly 90% of patients at week 96 of therapy. Baseline serum HBV-DNA is the major determinant of timetrends in virological response, with no significant influence of HBeAg, drug resistance mutations nor coinfection with hepatitis C or delta viruses. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Trevino A.,Hospital Carlos III | de Mendoza C.,Hospital Carlos III | Caballero E.,Hospital Vall dHebron | Rodriguez C.,Centro Sanitario Sandoval | And 6 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2011

Background: In contrast with HIV-1, information about drug resistance in HIV-2 is scarce and mainly derived from small series of patients failing antiretroviral therapy. Methods: The spectrum of changes in the reverse transcriptase (RT), protease (PR) and integrase (INT) genes was examined in HIV-2 individuals enrolled in the HIV-2 Spanish register. Results: From a total of 236 HIV-2-infected individuals registered in Spain from 1989 to June 2010, 53 PR, 44 RT and 8 INT sequences were obtained. Low plasma viraemia precluded collection of this information from most of the remaining cases. No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I and K219E). In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations. In PR the most frequent major changes were V47A (17%), I54M (17%), I82F (13%), L90M (29%) and L99F (29%). Two of the three patients who failed on raltegravir had N155H in the INT region. Conclusions: Drug resistance mutations in HIV-2 are selected at the same positions as in HIV-1, although with different frequency. Polymorphisms in the RT and PR associated with drug resistance in HIV-1 as compensatory changes are common in untreated HIV-2 subjects. These findings highlight the need for specific guidelines for interpreting genotypic resistance patterns in HIV-2 infection. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Rallon N.I.,Hospital Carlos III | Restrepo C.,Hospital Carlos III | Naggie S.,Duke Clinical Research Institute | Lopez M.,Hospital Carlos III | And 5 more authors.
AIDS | Year: 2011

The critical role of interleukin-28B (IL28B)/interferon-λ3 (IFN-λ3) polymorphisms on the susceptibility to hepatitis C virus infection and the response to peginterferon-ribavirin therapy has encouraged exploration of similar effects on other viruses. Given that IFN-λ mediates anti-HIV-1 activity, the protective role of IL28B polymorphisms was examined in 29 seronegative individuals at risk for HIV-infection and in 68 HIV-positive carriers with and without rapid progression of immunodeficiency. No protective role of IL28B polymorphism was found examining both HIV-disease progression and HIV-protection. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Yebra G.,Hospital Ramon Y Cajal | De Mulder M.,Hospital Ramon Y Cajal | Martin L.,Hospital Ramon Y Cajal | Rodriguez C.,Centro Sanitario Sandoval | And 7 more authors.
Journal of Clinical Microbiology | Year: 2012

HIV-1 groupMis classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02-AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Fernandez-Montero J.V.,Hospital Carlos III | Barreiro P.,Hospital Carlos III | Del Romero J.,Centro Sanitario Sandoval | Soriano V.,Hospital Carlos III
AIDS Reviews | Year: 2012

Though a large number of antiretrovirals have been developed for the treatment of HIV infection, new HIV infections continue to occur, especially among certain high-risk groups, such as men who have sex with men. Overall, the current estimated incidence of HIV infection is 2.5-fold higher than the number of individuals that begin antiretroviral therapy every year worldwide. Along with the personal drama caused by the diagnosis of HIV infection, other considerations in society, including economics and interpersonal relationships, make the need for HIV prevention strategies a priority. Though vaccines have shown great efficacy in the combat of other epidemics, currently there is no effective vaccine against HIV, and it is unlikely that any will become available in the near future. Thus, new approaches such as pre-exposure prophylaxis are viewed with increasing interest. The results from recent clinical trials have provided support in favor of distinct pre-exposure prophylaxis modalities. However, concerns exist about increasing risky behaviors and selection and spread of antiretroviral drug resistance with a broader use of pre-exposure prophylaxis. The aim of this review is to examine the evidence available on the effectiveness of pre-exposure prophylaxis and its potential influence on the HIV epidemics.


Trevino A.,Hospital Carlos III | De Mendoza C.,Hospital Carlos III | Parra P.,Hospital Carlos III | Rodriguez C.,Centro Sanitario Sandoval | And 5 more authors.
Antiviral Therapy | Year: 2011

Background: Direct acting antivirals (DAA) targeting the HCV serine protease and RNA polymerase have recently entered clinical development. Information about primary resistance to these compounds in HIV-HCV-coinfected patients is scarce. Methods: All individuals newly diagnosed with HIV-1 at several clinics in Madrid between 2000 and 2010 were tested for serum HCV antibody and HCV RNA. The NS3 protease and NS5B polymerase genes were sequenced in all HCV viraemic patients with genotype 1 (G1). Results: From 1,684 individuals newly diagnosed with HIV-1 during the 10-year study period, 141 (8.4%) were positive for serum HCV RNA. Overall, 58% were infected with G1, being 1a in 64.2% of them. Altogether, 62% of G1a and 30% of G1b harboured HCV drug-resistant changes, with the most common being prQ80K (n=9), prV55A (n=2), polC316Y/N (n=3) and polV499A (n=24). Although no primary resistance mutations were identified for HCV protease inhibitors or nucleoside analogues, mutations C316Y/N and V499A conferring resistance to some non-nucleoside analogues were found in 6% and 51% of G1 patients, respectively. Conclusions: Natural DAA resistance-associated mutations are frequently seen in HIV-HCV-coinfected individuals. Changes polV499A and prQ80K seem to be natural polymorphisms and their effect on treatment outcomes warrants further examination. However, drug resistance testing in HCV drug-naive individuals coinfected with HIV currently does not seem to be warranted before using HCV protease inhibitors and nucleoside analogues. More information is needed for HCV non-nucleoside analogues. ©2011 International Medical Press.


Restrepo C.,Hospital Carlos III | Rallon N.I.,Hospital Carlos III | Del Romero J.,Centro Sanitario Sandoval | Rodriguez C.,Centro Sanitario Sandoval | And 7 more authors.
Journal of Immunology | Year: 2010

HIV-specific T cells response and T cell activation are frequently seen in exposed seronegative individuals (ESN). In this study, we report HIV-specific response and level of T cell activation in ESN partners of HIV-infected patients presenting low or undetectable levels of HIV-RNA. We evaluated 24 HIV-serodiscordant couples. ESN were classified into three categories of exposure to HIV (very low, low, and moderate-high), considering levels of HIV-RNA in their infected partner and frequency of sexual high-risk practices within the last 12 mo. HIV-specific T cell responses and activation levels in T cell subsets were evaluated by flow cytometry. We reported that 54% of ESN had detectable HIV-specific T cells response, being the highest prevalence seen in the low exposure group (64%). Several T cell subsets were significantly increased in ESN when compared with controls: CD4+CD38+ (p = 0.006), CD4+ HLA-DR-CD38+ (p = 0.02), CD4+CD45RA+CD27+HLA-DR-CD38 + (p = 0.002), CD8+CD45RA+CD27 +CD38-HLA-DR+ (p = 0.02), and CD8 +CD45RA+CD27-CD38+HLA-DR + (p = 0.03). Activation of CD8+ T cells was increased in ESN with detectable HIV T cell responses compared with ESN lacking these responses (p = 0.04). Taken together, these results suggest that persistent but low sexual HIV exposure is able to induce virus-specific T cells response and immune activation in a high proportion of ESN, suggesting that virus exposure may occur even in conditions of maximal viral suppression in the HIV-infected partner. Copyright © 2010 by The American Association of Immunologists, Inc.


Casado C.,Institute Salud Carlos III | Colombo S.,University of Lausanne | Rauch A.,University of Bern | Martinez R.,University of Lausanne | And 6 more authors.
PLoS ONE | Year: 2010

Background: Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP). Methodology and Principal Findings: We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals. Conclusions: A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research. © 2010 Casado et al.

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