RESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. METHODS: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. RESULTS: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). CONCLUSION: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .
Asunto(s)
Vacunas contra el SIDA/administración & dosificación , Adenoviridae/inmunología , ADN Viral/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Plásmidos/inmunología , Vacunas de ADN/administración & dosificación , Vacunas contra el SIDA/efectos adversos , Vacunas contra el SIDA/genética , Vacunas contra el SIDA/inmunología , Adenoviridae/genética , Adolescente , Adulto , África Oriental , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Cultivadas , ADN Viral/genética , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/inmunología , VIH-1/genética , Proteínas del Virus de la Inmunodeficiencia Humana/genética , Proteínas del Virus de la Inmunodeficiencia Humana/inmunología , Humanos , Interferón gamma/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Plásmidos/genética , Vacunas de ADN/efectos adversos , Vacunas de ADN/genética , Vacunas de ADN/inmunología , Adulto JovenRESUMEN
We report a prospective comparison of human immunodeficiency virus type 1 testing by enzyme immunoassay and Western blot with four rapid tests of 486 subjects performed in rural Kenya. Rapid test sensitivity was 100%. Specificity ranged from 99.1 to 100%. Combined use of two Food and Drug Administration-approved rapid tests yielded a single false-positive result.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Infecciones por VIH/diagnóstico , VIH-1/aislamiento & purificación , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Western Blotting/métodos , Infecciones por VIH/epidemiología , Humanos , Técnicas para Inmunoenzimas/métodos , Kenia/epidemiología , Tamizaje Masivo/métodos , Valor Predictivo de las Pruebas , Prevalencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
As part of a program to determine the genetic diversity of human immunodeficiency virus in rural Kenya, we carried out a molecular analysis of the C2-V3 region of HIV-infected blood samples obtained from 30 antenatal clinic attendees of seven health centers in western Kenya. Direct sequencing was carried out on the envelope C2-V3 region of proviral DNA. On phylogenetic analysis with reference strains, 20 were subtype Al, 2 were subtype D, 1 was subtype C, 1 was subtype G, 1 was CRF-10, 2A/D, 2A/C, and 2 were unclassified. The presence of CRF-10 and the great variety of subtypes and recombinants in such a limited sample size suggest that western Kenya may be a potential hotspot for HIV recombination in the country.