RESUMO
BACKGROUND: Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV+ individuals could naturally also harbour low viral reservoirs. METHODS: We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with <50 HIV-DNA copies/106 PBMCs constitute the 'Low Viral Reservoir Treated' cohort (LoViReT). Longitudinal samples were obtained from 12 chronically treated LoViReT and compared to 13 controls (>50 HIV-DNA copies/106 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. FINDINGS: We found that 9.3% of the individuals screened had <50 HIV-DNA copies/106 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8+ TTM and TEMRA in the absence of cART, and higher CD8+ TN after 18 months on therapy. INTERPRETATION: Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8+ T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. FUNDING: MSD Spain.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Reservatórios de Doenças/virologia , Infecções por HIV/tratamento farmacológico , Viremia/tratamento farmacológico , Adulto , Fármacos Anti-HIV/efeitos adversos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Leucócitos Mononucleares/virologia , Masculino , Espanha/epidemiologia , Carga Viral/efeitos dos fármacos , Viremia/sangue , Viremia/virologiaRESUMO
Mycoplasma pneumoniae is a human pathogen with worldwide distribution. This microorganism is a common cause (10-30%) of community-acquired pneumonia, also called primary atypical pneumonia because of the spectrum of clinical and radiological findings. The immune response is mainly based on rapid antibody production against peptide and glycolipid antigens derived from this microorganism. During the primary infection, IgM levels generally rise within the first week, and are then followed by an IgG response. Titers of IgG and IgA increase in reinfections. Microbiological diagnosis is based on specific antibody detection. Polymerase chain reaction (PCR) techniques performed on sputum or pharyngeal/nasopharyngeal exudates, as well as the development of multiplex PCR reactions allowing identification of M. pneumoniae and other respiratory pathogens, would by highly useful in routine diagnosis. The most common serological techniques are complement fixation, immunofluorescence, particle agglutination, and enzyme immunoassay. Diagnosis should be performed by selecting the most appropriate test according to functional criteria and population groups. Specific detection of IgM antibodies should not be included in the differential diagnosis in adults and young people. Diagnostic criteria including seroconversion or rising IgG titers may not be clinically useful, because of the time delay and the difficulty of obtaining a second serum specimen for testing, given the mildness of the clinical symptoms.