Early HIV Infection: Recognizing the not so obvious with no time to lose
Read
12356
Timeswas read the article
1215
Total PDF
11141
Total HTML
Share statistics
array:20 [ "pii" => "13087292" "issn" => "0213005X" "doi" => "10.1016/S0213-005X(06)73766-1" "estado" => "S300" "fechaPublicacion" => "2006-04-01" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Enferm Infecc Microbiol Clin. 2006;24:222-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3045 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 2526 "PDF" => 507 ] ] "itemSiguiente" => array:16 [ "pii" => "13087293" "issn" => "0213005X" "doi" => "10.1016/S0213-005X(06)73767-3" "estado" => "S300" "fechaPublicacion" => "2006-04-01" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Enferm Infecc Microbiol Clin. 2006;24:225-31" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3352 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 2895 "PDF" => 447 ] ] "es" => array:11 [ "idiomaDefecto" => true "titulo" => "Utilización en la práctica clínica de los tests de resistencia genotípica al VIH-1. Factores predictivos de mala evolución virológica en tratamientos de rescate" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "225" "paginaFinal" => "231" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Clinical use of HIV-1 resistance genotyping. Predictive factors of poor virological evolution in salvage treatments" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Melcior Riera-Jaume, María Peñaranda-Vera, Mª Angels Ribas-Blanco, Javier Murillas-Angoiti, Antoni Campins, Ana Salas-Aparicio, María Leyes-García, Antonio Pareja-Bezares, José Luis Pérez, Concepción Villalonga-Pieras" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Melcior" "apellidos" => "Riera-Jaume" ] 1 => array:2 [ "nombre" => "María" "apellidos" => "Peñaranda-Vera" ] 2 => array:2 [ "nombre" => "Mª Angels" "apellidos" => "Ribas-Blanco" ] 3 => array:2 [ "nombre" => "Javier" "apellidos" => "Murillas-Angoiti" ] 4 => array:2 [ "nombre" => "Antoni" "apellidos" => "Campins" ] 5 => array:2 [ "nombre" => "Ana" "apellidos" => "Salas-Aparicio" ] 6 => array:2 [ "nombre" => "María" "apellidos" => "Leyes-García" ] 7 => array:2 [ "nombre" => "Antonio" "apellidos" => "Pareja-Bezares" ] 8 => array:2 [ "nombre" => "José Luis" "apellidos" => "Pérez" ] 9 => array:2 [ "nombre" => "Concepción" "apellidos" => "Villalonga-Pieras" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/13087293?idApp=UINPBA00004N" "url" => "/0213005X/0000002400000004/v0_201307121514/13087293/v0_201307121514/es/main.assets" ] "itemAnterior" => array:16 [ "pii" => "13087291" "issn" => "0213005X" "doi" => "10.1016/S0213-005X(06)73765-X" "estado" => "S300" "fechaPublicacion" => "2006-04-01" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Enferm Infecc Microbiol Clin. 2006;24:219-21" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3925 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 3438 "PDF" => 477 ] ] "es" => array:9 [ "idiomaDefecto" => true "titulo" => "Tests de resistencia genotípica en pacientes con fracaso terapéutico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "219" "paginaFinal" => "221" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Resistance genotyping in patients with therapeutic failure" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cecilia Cabrera, Bonaventura Clotet" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Cecilia" "apellidos" => "Cabrera" ] 1 => array:2 [ "nombre" => "Bonaventura" "apellidos" => "Clotet" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/13087291?idApp=UINPBA00004N" "url" => "/0213005X/0000002400000004/v0_201307121514/13087291/v0_201307121514/es/main.assets" ] "en" => array:9 [ "idiomaDefecto" => true "titulo" => "Early HIV Infection: Recognizing the not so obvious with no time to lose" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "222" "paginaFinal" => "224" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Peter A Leone" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Peter A" "apellidos" => "Leone" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Associate Professor of Medicine. University of North Carolina. Medical Director. North Carolina HIV/STD Prevention and Care Branch. North Carolina Department of Health and Human Services. EE.UU." "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "textoCompleto" => "<p class="elsevierStylePara">Acute HIV infection (AHI) refers to the brief period after HIV infection when HIV RNA first appears in the blood but before HIV specific antibodies are detectable. Individuals with AHI have increased HIV transmissibility due to the increased viral load in both blood and genital secretions, making it centrally important for prevention of secondary HIV transmission <span class="elsevierStyleSup">1</span>. While some patients with acute infection have a viral syndrome (known as acute retroviral syndrome or primary HIV); the mild and non-specific nature of acute retroviral syndrome complicates effective screening <span class="elsevierStyleSup">2</span>. A significant barrier to diagnosis of AHI is the non-specific nature of the signs and symptoms associated with the acute retroviral syndrome. Unless a clinician entertains the diagnosis in the differential and orders an appropriate diagnostic test, the diagnosis will be missed. It is vital to have clinicians consider AHI in young adults with fever and diffuse lymphadenopathy and that clinicians also know to include a viral specific test and not just an HIV antibody as diagnostic tests. Methods to incorporate HIV RNA screening of all HIV antibody negative bloods for testing populations may reduce the number of missed diagnosis for AHI. Specimen pooling and nucleic acid amplification methodologies have proven to be a feasible and effective method of acute HIV infection screening of at risk populations such as individuals seen in Sexually Transmitted Disease clinics, Emergency Departments, and at other locations where HIV testing is routinely provided or individuals at risk for HIV infection may seek care <span class="elsevierStyleSup"> 3</span>.</p><p class="elsevierStylePara">Diagnosing AHI is of benefit at the level of the individual patient and at the level of the general public as part of HIV disease control efforts. Early HIV therapy presents a potential window of opportunity to improve immune function and slow the progression to AIDS, and more trials are underway now to determine the clinical benefits of early HIV therapy <span class="elsevierStyleSup">4,5</span>. Transmission of HIV is principally driven by the quantity of the HIV inoculum in either blood or genital secretions. This brief period of extremely high HIV viral load and uncontrolled viral replication in AHI last for less than eight weeks. Therapy with ARV can precipitously drop the serum and genital secretion viral load and potentially render the individual "non-infectious" should the viral load drop below detection. Additional public health benefits include epidemiologic information about incidence rates in communities <span class="elsevierStyleSup">6</span>, case clustering <span class="elsevierStyleSup">7</span>, information on trends in drug resistance <span class="elsevierStyleSup"> 8</span>, identification of high risk periods and places <span class="elsevierStyleSup"> 9,10</span>, molecular characterization to better define core populations and sexual risk <span class="elsevierStyleSup">11</span>, identification of marginalized and otherwise hidden high risk groups <span class="elsevierStyleSup">12</span>, and a unique opportunity to disrupt active HIV transmission networks.</p><p class="elsevierStylePara">The kinetics of HIV transmission and diagnosis has profound implications for disease control efforts <span class="elsevierStyleSup">13,14</span>. The biological progression and behavioral characteristics leading to AHI as well as concomitant sexually transmitted infections exacerbate the risk of secondary HIV transmission <span class="elsevierStyleSup">15</span>. As higher viral loads correlate to greater risk of HIV transmission, the increased viral burden in blood and genital secretions associated with AHI increase the probability of transmission <span class="elsevierStyleSup"> 1,16</span>. "Look-back" studies investigating transmission rates <span class="elsevierStyleSup">17</span>, case series showing rapid secondary transmission <span class="elsevierStyleSup">18</span>, and prospective sero-discordant couple studies <span class="elsevierStyleSup"> 19</span> all strongly suggest a greater likelihood of transmission per sex act during acute HIV infection. Our own data from the North Carolina AHI program (STAT) suggest transmission of HIV during acute infection occurred > 1:13 to 1:18 unprotected coital acts. Beyond the increased risk of transmission from an individual with AHI, the partners subsequently infected during this period are also at an increased risk of transmitting HIV, creating a chain of secondary transmission among core populations <span class="elsevierStyleSup">20</span>.</p><p class="elsevierStylePara">In addition to this heightened biological risk of HIV derived from increased viremia among specific populations, increased behavioral risk has also been suggested during the AHI. Studies analyzing MSM who recently seroconverted revealed behaviors during the period of acute HIV infection which likely facilitated HIV transmission, and declined soon after diagnosis <span class="elsevierStyleSup">21</span>. This behavioral component of HIV risk is independent of viremia, but importantly seems to correspond to a similar period of high risk behavior. Recall bias interferes with locating active HIV transmission networks since it tends to increase as time elapses from sexual encounter <span class="elsevierStyleSup">22</span>. Finding individuals with AHI at the earliest time following infection is urgent both for the public health and individual wellbeing.</p><p class="elsevierStylePara">Sued et al, in their paper describe the epidemiologic and clinical characteristics of cohort of patients with AHI whom they followed prospectively. This represented nearly 3% of all new HIV infections diagnosed during a seven year time period. The symptoms were nonspecific with only fever and asthenia being nearly universal (98% and 86% respectively) <span class="elsevierStyleSup">23</span>. Prior studies suggest symptoms of an acute retroviral syndrome occur in 40-90% of patients <span class="elsevierStyleSup">13</span>. Our own experience in North Carolina found that 70% of individuals developed an acute retroviral illness but that less than 50% had symptoms at the time of diagnosis. The development of symptoms is associated with high-level viremia and the initial immune response to HIV. Much is unknown regarding the prognostic significance of the acute retroviral syndrome but the severity of illness may reflect difficulty of the host immune response to control viral replication and has been correlated with a more rapid progression of disease <span class="elsevierStyleSup">13</span>. Sued, et al provide further support for this conclusion with the more rapid progression of disease reported in those who did not receive ART (42.3% vs. 12.3%) <span class="elsevierStyleSup">23</span>. It is, for this reason, disturbing that the percentage of individuals starting on ART decreased during the observed period from 79% to 49%. The high rate of dyslipidemia and lipodistrophy may be attributable to the choice of ART or reflect a "defect" in the host immune response with poor response to viral replication since the majority of the individuals in the cohort had an acute retroviral syndrome.</p><p class="elsevierStylePara">The timing of HIV diagnosis is central to subsequent public health response and preventing unknowing transmission of HIV. Depending on the threshold used for a true positive, nucleic acid amplification testing (NAAT) used for acute HIV surveillance can be positive within the first week of infection. Some third generation ELISA tests may be positive as early as three weeks following HIV infection, compared to the two weeks needed for positive p24 antigenemia <span class="elsevierStyleSup">16</span>. The sensitivity of assay used to detect either HIV or HIV specific antibody response is only one factor in diagnosing acute HIV. The frequency of repeat HIV testing in high risk groups will also impact the ability to diagnosis individuals during the AHI period. Clinician awareness of the presentation of AHI as well as a high index of suspicion is also critical since detectable antibodies levels may not be present at the maximal height of viremia and the onset of symptoms. Appropriate clinical history such as sexual risk factors reported intravenous drug use coupled with physical signs and symptoms of an acute retroviral illness should prompt the ordering of appropriate diagnostic tests. Sued and colleagues looked for evidence of AHI in this high risk population and therefore were able to recognize and diagnose AHI.</p><p class="elsevierStylePara">The University of North Carolina Hospitals recently implemented routine HIV RNA screening of all HIV ELISA antibody negative or Western Blot indeterminate blood as a way of reducing clinician oversight of AHI. When used with specimen pooling, HIV NAAT offers a sensitive and specific method for detection of acute HIV infection before the period of greatest transmissibility <span class="elsevierStyleSup">3,23</span>. North Carolina's STAT program illustrates how acute HIV surveillance is critically time dependent. During the period November 2002 to November 2005, 63 patients from 110 public counseling and testing sites were RNA positive and antibody negative. Finding individuals with acute HIV infection and their recent sexual partners provides insight about HIV sexual networks at the leading edge of the epidemic. From a public health perspective, the evidence to support increased HIV transmissibility during acute infection justifies closely related case finding and prevention activities.</p><p class="elsevierStylePara">The clinical presentation of AHI is, at best, non-specific and can closely resemble a host of other "viral-like" illness. A history of recent unprotected sexual intercourse or injecting drug use coupled with characteristic signs/symptoms such as fever, rash or lymphadenopathy should alert clinicians to consideration of the diagnosis. Education of clinicians and patients concerning acute retroviral syndrome and access to frequent HIV testing is critical for identification of AHI.</p><p class="elsevierStylePara">Closing the window period between acquisition and diagnosis of HIV infection via routine acute HIV infection screening is a major public health opportunity that demands further study and consideration. Case interviewing needs to be better connected to HIV prevention, given what we know about the increased HIV transmissibility associated with acute HIV infection. In most parts of the world, physicians fail to diagnose acute HIV infection; case interviewing is underutilized; and disease control based on acute HIV surveillance remains a theoretical benefit. Since the increased HIV transmissibility associated with acute HIV infection is supported by North Carolina's STAT program <span class="elsevierStyleSup">3</span> and transmission data, identifying acute HIV infections and tracing their partners should be further considered. Analyzing the high-risk people/places/periods involved in active HIV transmission needs to be considered in other locations, as a complementary strategy alongside the sensitive-less sensitive HIV testing. Despite support from the US CDC and work in the field, routine detection of acute HIV infection and case interviewing has not yet been broadly applied.</p><p class="elsevierStylePara">Some have persistent doubts about acute HIV centered testing and disease control. Limitations to the proposed approach include higher testing costs, NAAT test performance issues, and a requisite venous blood draw. In addition, the need for follow-up Western Blot confirmation for presumably positive clients makes anonymous testing difficult. Given the increased uptake associated with rapid HIV testing, the longer follow-up and potentially greater refusal of blood draws required for acute HIV screening, strategies to incorporate AHI screening seems justified. North Carolina's STAT program has shown that identification of acute HIV infections and disease control can be implemented on a very large scale while preserving test performance and low cost. Sued and associates demonstrate an additional approach by prospective following of high risk groups with the hope of recognizing AHI. Even with the increased cost and potentially higher refusal rate associated with this strategy, the public health advantages demand further study and consideration of these new approaches.</p><p class="elsevierStylePara">Extensive public health experience with syphilis control suggests that disease control focused epidemiologic investigations linked to active transmission among core high risk groups may be a more effective public health approach to HIV control then merely recommending universal HIV testing. While traditional HIV surveillance systems provide broader estimates of overall HIV incidence, such surveys are very unlikely to adequately sample either populations that deny high risk behaviors or high morbidity areas to provide the type of detailed information essential to stopping active transmission networks.</p><p class="elsevierStylePara">Acute HIV infection detection and disease control systems allow clinicians and public health authorities to get a more detailed and comprehensive understanding of the when, where, why, and who of new HIV infections. Routine detection of acute HIV and disease control offers a new blueprint for organizing HIV testing, bringing HIV acquisition and diagnosis closer, and expanding potential prevention programs. Several lines of evidence support a new paradigm of acute HIV detection and disease control, but more investigation and further replication are necessary.</p><hr></hr><p class="elsevierStylePara"> Correspondence: Peter A. Leone, MD.<br></br> University of North Carolina.<br></br> Campus Box #7030. 130 Mason Farm Road.<br></br> Chapel Hill: North Carolina 27599-7030. EE.UU.<br></br> E-mail: <a href="mailto:zu.leone@gmail.com" class="elsevierStyleCrossRefs"> zu.leone@gmail.com</a></p><p class="elsevierStylePara">Manuscrito recibido el 10-2-2006; aceptado el 15-2-2006.</p>" "pdfFichero" => "28v24n04a13087292pdf001.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Brief but efficient: acute HIV infection and the sexual transmission of HIV." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Pilcher CD" 1 => "Tien HC" 2 => "Eron JJ" 3 => "Vernazza PL" 4 => "Leu Sy" 5 => "Stewart PW" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/386333" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2004" "volumen" => "189" "paginaInicial" => "1785" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15122514" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Infrequent Diagnosis of Primary HIV Immunodeficiency Infection." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Weintrob AC" 1 => "Giner J" 2 => "Menezes P" 3 => "Patrick E" 4 => "Benjamin DK" 5 => "Lennox J" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Int Med" "fecha" => "2003" "volumen" => "163" "paginaInicial" => "2097" "paginaFinal" => "100" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Detection of acute infections during HIV testing in North Carolina." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Pilcher CD" 1 => "Fiscus SA" 2 => "Nguyen TQ" 3 => "Foust E" 4 => "Wolf L" 5 => "Williams D" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa042291" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "352" "paginaInicial" => "1873" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15872202" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Immune control of HIV-1 after early treatment of acute infection." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Rosenberg E" 1 => "Altfeld M" 2 => "Poon S" 3 => "Phillips MN" 4 => "Wilkes BM" 5 => "Eldridge RL" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/35035103" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2000" "volumen" => "407" "paginaInicial" => "523" "paginaFinal" => "6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11029005" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD4 and CD8 T lymphocytes." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Oxenius A" 1 => "Price D" 2 => "Easterbrook P" 3 => "O'Callaghan CA" 4 => "Kelleher AD" 5 => "Whelan JA" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "PNAS" "fecha" => "2000" "volumen" => "97" "paginaInicial" => "3382" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10737796" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The Unexpected Movement of the HIV Epidemic in the Southeastern United States: Transmission Among College Students." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Hightow LB" 1 => "MacDonald P" 2 => "Pilcher CD" 3 => "Leone PA." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAIDS" "fecha" => "2005" "volumen" => "38" "paginaInicial" => "531" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15793362" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Acute HIV infection: impact on the spread of HIV and transmission of drug resistance." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Yerly S" 1 => "Vora S" 2 => "Rizzardi P" 3 => "Chave JP" 4 => "Vernazza PL" 5 => "Flepp M" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2001" "volumen" => "15" "paginaInicial" => "2287" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11698702" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "al. Antiretroviral-drug resistance among patients recently infected with HIV." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Little SJ" 1 => "Holte S" 2 => "Routy JP" 3 => "Daar ES" 4 => "Markowitz M" 5 => "Collier AC" 6 => "et." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa013552" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "347" "paginaInicial" => "385" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12167680" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary HIV Infection ­ A Public Health Opportunity." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Cates W" 1 => "Chesney MA" 2 => "Cohen MS." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "AJPH" "fecha" => "1997" "volumen" => "87" "paginaInicial" => "1928" "paginaFinal" => "30" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Acute HIV revisited: new opportunities for treatment and prevention." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Pilcher CD" 1 => "Eron JJ" 2 => "Galvin S" 3 => "Gay C" 4 => "Cohen MS." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI21540" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2004" "volumen" => "113" "paginaInicial" => "937" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15057296" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Transmission of HIV-1 during primary infection: relationship to sexual risk and sexually transmitted infections." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Pao D" 1 => "Fisher M" 2 => "Hue S" 3 => "Dean G" 4 => "Murphy G" 5 => "Cane PA" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2005" "volumen" => "19" "paginaInicial" => "85" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15627037" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "HIV transmission among black college student and non-student men who have sex with men­North Carolina, 2003." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Centers for Disease Control and Prevention." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "MMWR Morb Mortal Wkly Rep" "fecha" => "2004" "volumen" => "53" "paginaInicial" => "731" "paginaFinal" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15318156" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary HIV type 1 infection." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Kassutto S" 1 => "Rosenberg ES." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/420745" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2004" "volumen" => "38" "paginaInicial" => "1447" "paginaFinal" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15156484" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Transmission, acute HIV-1 infection and the quest for strategies to prevent infection." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Pope M" 1 => "Haase AT." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nm0703-847" "Revista" => array:6 [ "tituloSerie" => "Nat Med" "fecha" => "2003" "volumen" => "9" "paginaInicial" => "847" "paginaFinal" => "52" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12835704" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The role of sexually transmitted diseases in HIV transmission." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Galvin SR" 1 => "Cohen MS." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrmicro794" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Microbiol" "fecha" => "2004" "volumen" => "2" "paginaInicial" => "33" "paginaFinal" => "42" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15035007" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Saville RD" 1 => "Constantine NT" 2 => "Cleghorn FR" 3 => "Jack N" 4 => "Bartholomew C" 5 => "Edwards J" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.39.7.2518-2524.2001" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2001" "volumen" => "39" "paginaInicial" => "2518" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11427563" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Leynaert B" 1 => "Downs AM" 2 => "De Vincenzi I." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Epidemiol" "fecha" => "1998" "volumen" => "148" "paginaInicial" => "88" "paginaFinal" => "96" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9663408" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Sexual transmission during the incubation period of primary HIV infection." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Pilcher CD" 1 => "Eron JJ Jr" 2 => "Vemazza PL" 3 => "Battegay M" 4 => "Harr T" 5 => "Yerly S" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2001" "volumen" => "286" "paginaInicial" => "1713" "paginaFinal" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11594895" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Wawer MJ" 1 => "Gray RH" 2 => "Sewankambo NK" 3 => "Serwadda D" 4 => "Xianbin L" 5 => "Laeyewdecker O" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/429411" "Revista" => array:6 [ "tituloSerie" => "JID" "fecha" => "2005" "volumen" => "191" "paginaInicial" => "1403" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15809897" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The role of early HIV infection in the spread of HIV through populations." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Koopman JS" 1 => "Jacquez JA" 2 => "Welch GW" 3 => "Simon CP" 4 => "Foxman B" 5 => "Pollock SM" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Acquir Immune Defic Syndr" "fecha" => "1997" "volumen" => "14" "paginaInicial" => "249" "paginaFinal" => "58" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Colfax GN" 1 => "Buchbinder SP" 2 => "Cornelisse PG" 3 => "Vittinghoff E" 4 => "Mayer K" 5 => "Celum C." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2002" "volumen" => "16" "paginaInicial" => "1529" "paginaFinal" => "35" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12131191" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Reliability of partner reports of sexual history in a heterosexual population at a sexually transmitted diseases clinic." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Ellish NJ" 1 => "Weisman CS" 2 => "Celentano D" 3 => "Zenilman JM." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Sex Transm Dis" "fecha" => "1996" "volumen" => "23" "paginaInicial" => "446" "paginaFinal" => "52" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8946627" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary human immunodeficiency virus type 1 infection: clinical, virological and immunological characteristics of 75 patients (1997-2003)." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:8 [ 0 => "Sued O" 1 => "Mir.o" 2 => "JM" 3 => "Alquezar A" 4 => "Claramonte X" 5 => "García F" 6 => "Plana M" 7 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Enferm Infecc Microbiol Clin" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "238" "paginaFinal" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16725083" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Feasibility of pooling sera for HIV-1 viral RNA to diagnose acute primary HIV-1 infection and estimate HIV incidence." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Quinn TC" 1 => "Brookmeyer R" 2 => "Kline R" 3 => "Shepherd M" 4 => "Parahjape R" 5 => "Mehendale S" 6 => "et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2000" "volumen" => "14" "paginaInicial" => "2751" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11125894" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/0213005X/0000002400000004/v0_201307121514/13087292/v0_201307121514/en/main.assets" "Apartado" => array:4 [ "identificador" => "15248" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/0213005X/0000002400000004/v0_201307121514/13087292/v0_201307121514/en/28v24n04a13087292pdf001.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/13087292?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 142 | 12 | 154 |
| 2024 September | 278 | 23 | 301 |
| 2024 August | 212 | 28 | 240 |
| 2024 July | 225 | 15 | 240 |
| 2024 June | 179 | 11 | 190 |
| 2024 May | 203 | 11 | 214 |
| 2024 April | 228 | 11 | 239 |
| 2024 March | 256 | 8 | 264 |
| 2024 February | 291 | 13 | 304 |
| 2024 January | 290 | 13 | 303 |
| 2023 December | 227 | 11 | 238 |
| 2023 November | 333 | 15 | 348 |
| 2023 October | 255 | 13 | 268 |
| 2023 September | 192 | 9 | 201 |
| 2023 August | 177 | 8 | 185 |
| 2023 July | 164 | 6 | 170 |
| 2023 June | 188 | 8 | 196 |
| 2023 May | 187 | 11 | 198 |
| 2023 April | 178 | 6 | 184 |
| 2023 March | 164 | 16 | 180 |
| 2023 February | 132 | 11 | 143 |
| 2023 January | 143 | 16 | 159 |
| 2022 December | 197 | 11 | 208 |
| 2022 November | 223 | 20 | 243 |
| 2022 October | 179 | 19 | 198 |
| 2022 September | 207 | 21 | 228 |
| 2022 August | 186 | 10 | 196 |
| 2022 July | 142 | 23 | 165 |
| 2022 June | 85 | 15 | 100 |
| 2022 May | 117 | 18 | 135 |
| 2022 April | 139 | 30 | 169 |
| 2022 March | 115 | 9 | 124 |
| 2022 February | 108 | 12 | 120 |
| 2022 January | 116 | 6 | 122 |
| 2021 December | 132 | 16 | 148 |
| 2021 November | 165 | 22 | 187 |
| 2021 October | 227 | 26 | 253 |
| 2021 September | 143 | 10 | 153 |
| 2021 August | 147 | 17 | 164 |
| 2021 July | 165 | 9 | 174 |
| 2021 June | 133 | 13 | 146 |
| 2021 May | 111 | 13 | 124 |
| 2021 April | 182 | 6 | 188 |
| 2021 March | 142 | 11 | 153 |
| 2021 February | 88 | 13 | 101 |
| 2021 January | 83 | 13 | 96 |
| 2020 December | 62 | 8 | 70 |
| 2020 November | 44 | 8 | 52 |
| 2020 October | 43 | 2 | 45 |
| 2020 September | 41 | 9 | 50 |
| 2020 August | 55 | 6 | 61 |
| 2020 July | 34 | 9 | 43 |
| 2020 June | 28 | 5 | 33 |
| 2020 May | 40 | 6 | 46 |
| 2020 April | 37 | 6 | 43 |
| 2020 March | 47 | 8 | 55 |
| 2020 February | 26 | 4 | 30 |
| 2020 January | 22 | 8 | 30 |
| 2019 December | 18 | 17 | 35 |
| 2019 November | 12 | 13 | 25 |
| 2019 October | 10 | 9 | 19 |
| 2019 September | 27 | 2 | 29 |
| 2019 August | 4 | 9 | 13 |
| 2019 July | 24 | 9 | 33 |
| 2019 June | 20 | 15 | 35 |
| 2019 May | 64 | 53 | 117 |
| 2019 April | 16 | 23 | 39 |
| 2019 March | 12 | 3 | 15 |
| 2019 February | 9 | 5 | 14 |
| 2019 January | 12 | 6 | 18 |
| 2018 December | 11 | 9 | 20 |
| 2018 November | 10 | 4 | 14 |
| 2018 October | 23 | 10 | 33 |
| 2018 September | 11 | 3 | 14 |
| 2018 August | 4 | 0 | 4 |
| 2018 July | 8 | 1 | 9 |
| 2018 June | 2 | 2 | 4 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 0 | 3 | 3 |
| 2018 March | 2 | 1 | 3 |
| 2018 February | 10 | 0 | 10 |
| 2018 January | 15 | 2 | 17 |
| 2017 December | 7 | 1 | 8 |
| 2017 November | 9 | 3 | 12 |
| 2017 October | 6 | 5 | 11 |
| 2017 September | 10 | 8 | 18 |
| 2017 August | 7 | 9 | 16 |
| 2017 July | 18 | 1 | 19 |
| 2017 June | 18 | 15 | 33 |
| 2017 May | 16 | 10 | 26 |
| 2017 April | 19 | 3 | 22 |
| 2017 March | 13 | 38 | 51 |
| 2017 February | 11 | 0 | 11 |
| 2017 January | 16 | 1 | 17 |
| 2016 December | 15 | 4 | 19 |
| 2016 November | 23 | 1 | 24 |
| 2016 October | 40 | 6 | 46 |
| 2016 September | 49 | 4 | 53 |
| 2016 August | 16 | 4 | 20 |
| 2016 July | 11 | 1 | 12 |
| 2016 June | 23 | 1 | 24 |
| 2016 May | 16 | 9 | 25 |
| 2016 April | 13 | 16 | 29 |
| 2016 March | 23 | 9 | 32 |
| 2016 February | 17 | 11 | 28 |
| 2016 January | 25 | 19 | 44 |
| 2015 December | 28 | 9 | 37 |
| 2015 November | 22 | 6 | 28 |
| 2015 October | 27 | 10 | 37 |
| 2015 September | 30 | 7 | 37 |
| 2015 August | 12 | 4 | 16 |
| 2015 July | 19 | 3 | 22 |
| 2015 June | 5 | 2 | 7 |
| 2015 May | 12 | 3 | 15 |
| 2015 April | 23 | 8 | 31 |
| 2015 March | 14 | 16 | 30 |
| 2015 February | 7 | 2 | 9 |
| 2015 January | 21 | 3 | 24 |
| 2014 December | 26 | 7 | 33 |
| 2014 November | 22 | 4 | 26 |
| 2014 October | 19 | 4 | 23 |
| 2014 September | 17 | 4 | 21 |
| 2014 August | 15 | 7 | 22 |
| 2014 July | 21 | 4 | 25 |
| 2014 June | 27 | 0 | 27 |
| 2014 May | 11 | 3 | 14 |
| 2014 April | 8 | 0 | 8 |
| 2014 March | 13 | 0 | 13 |
| 2014 February | 12 | 0 | 12 |
| 2014 January | 20 | 2 | 22 |
| 2013 December | 15 | 1 | 16 |
| 2013 November | 22 | 2 | 24 |
| 2013 October | 15 | 1 | 16 |
| 2013 September | 20 | 3 | 23 |
| 2013 August | 24 | 2 | 26 |
| 2013 July | 21 | 2 | 23 |
| 2006 March | 1189 | 0 | 1189 |
Show all
