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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.


Rallon N.I.,Charles III University of Madrid | Restrepo C.,Charles III University of Madrid | Naggie S.,Duke Clinical Research Institute | Lopez M.,Charles III University of Madrid | 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.


Trevino A.,Hospital Carlos III | de Mendoza C.,Hospital Carlos III | Caballero E.,Service of Microbiology | 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.


Sierra-Enguita R.,Hospital Carlos III | Rodriguez C.,Centro Sanitario Sandoval | Aguilera A.,Hospital Conxo CHUS | Gutierrez F.,University Miguel Hernandez | 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.


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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