RESUMO
HIV infection is increasing in minority groups, particularly in African American and Hispanic women. Although the incidence of HIV dementia has decreased since the advent of highly active antiretroviral treatment, prevalence of neurocognitive complications has increased as patients are now living longer. This study's purpose was to determine the psychometric properties of the Spanish-language HIV Dementia Scale (HDS) in a group of HIV-infected women. We recruited 96 women: 60 HIV-seropositive and 36 HIV-seronegative. Modification of the HDS into a Spanish-language version consisted of translating the instructions, substituting four words in Spanish (gato, media, azul, piña), increasing 1 second in the psychomotor speed because the Spanish alphabet has more letters than the English alphabet, and not offering clues for memory recall. Cognitive impairment (CI) was defined according to the modified American Academy of Neurology HIV-dementia criteria including an asymptomatic CI group. Statistical analysis consisted of analysis of variance to determine group differences and receiver operator characteristics (ROC) to determine the optimal cutoff point for the screening of CI. HDS-Spanish total score and subscores for psychomotor speed and memory recall showed significant differences between HIV-seronegative and women with HIV-dementia (p < 0.001) and between HIV-seropositive women with normal cognition and those with HIV-dementia (p < 0.001). The optimal cutoff point of 13 or less had performance characteristics of 87% sensitivity and 46% specificity for HIV-associated CI (50.0% positive predictive value, 85.0% negative predictive value). The HDS-Spanish translation offers a useful screening tool with value for the identification of Hispanic women at risk of developing HIV-associated symptomatic neurocognitive disturbances.
Assuntos
Complexo AIDS Demência/classificação , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/epidemiologia , Adulto , Depressão/classificação , Feminino , Soronegatividade para HIV , Soropositividade para HIV , Humanos , Testes de Inteligência , Memória , Pessoa de Meia-Idade , Estudos Prospectivos , Psicometria , Desempenho Psicomotor , Porto Rico/epidemiologia , Curva ROC , Reprodutibilidade dos TestesRESUMO
HIV-1 vertical transmission in Puerto Rico has decreased significantly due to the implementation of antiviral therapy. Several studies have shown that the phenotype of the HIV-1 isolates initially recovered from infected infants has generally been one that replicates rapidly, infects macrophages, and preferentially use the CCR5 coreceptor. Our hypothesis is that viral genotypic and phenotypic differences exist between HIV-1 nontransmitter and transmitter mothers. Viral DNA samples and virus isolates were analyzed from a Puerto Rican perinatal population. Heteroduplex tracking assay (HTA) was performed on DNA samples to detect env V3 evolutionary variants and the extent of heterogeneity within each sample. HIV-1 C2-V3 variants were cloned from each patient to study sequence variation among the groups. Differences in replication kinetics of viral isolates in macrophage and GHOST CCR5 cells were analyzed by use of repeated measures linear regression analysis. HTA analysis showed that only two nontransmitter patient samples showed the presence of evolutionary variants. Phylogenetic analysis between maternal-infant pairs showed that transmission of a single maternal variant occurred, with the exception of one sample pair. When evaluating amino acid sequences from cloned PCR products, nontransmitting mothers appear to have a higher number of distinct sequences than both the transmitting mothers (p = 0.0410) and the infected infants (p = 0.0315). Analysis of replication kinetics indicated that transmitters showed faster replication kinetics in GHOST CCR5 cell cultures at 12 days postinfection (p = 0.0434) and 15 days postinfection (p = 0.0181). In conclusion, viral homogeneity and rapid replication kinetics were correlated with vertical transmission.
Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , HIV-1/classificação , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Feminino , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , HIV-1/fisiologia , Humanos , Cinética , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Filogenia , Gravidez , Fatores de Risco , Replicação ViralRESUMO
The chemokine receptors CCR5 and CXCR4 play a key role in HIV-1 infection as co-receptors for viral entry. In the placenta, an important natural barrier to HIV, the expression and regulation of these receptors has yet to be elucidated. In this study, we determined the expression of CCR5 and CXCR4 co-receptors on placental macrophages (PM) and the effect of interleukin-10 (IL-10) on co-receptor expression. PM were isolated from term placentae of HIV-uninfected mothers and cultured for up to 11 days. The cells were stimulated with IL-10 for 24 h and stained with specific antibodies to CCR5, CXCR4, CD4, CD3, CD11c and CD14 for flow cytometry. Unstimulated PM expressed significantly more CCR5 than CXCR4. Expression of both co-receptors was upregulated by stimulation with IL-10 at 24 h post-stimulation. In vivo expression of these co-receptors from frozen sections revealed a higher percentage of CCR5 positive cells. This is the first study in which expression of both co-receptors is detected on the PM membrane. These results are consistent with previous studies performed in our laboratory where PM were readily infected by CCR5-using HIV strains but could not be productively infected by HIV strains that exclusively use CXCR4 as a co-receptor.
Assuntos
Interleucina-10/farmacologia , Macrófagos/metabolismo , Placenta/metabolismo , Receptores CCR5/biossíntese , Receptores CXCR4/biossíntese , Síndrome da Imunodeficiência Adquirida/transmissão , Adulto , Células Cultivadas , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Processamento de Imagem Assistida por Computador , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Placenta/citologia , Placenta/efeitos dos fármacos , Gravidez , Complicações Infecciosas na Gravidez , Proteínas RecombinantesRESUMO
In this study, HIV-1 variants from a cohort of forty-eight Puerto Rican pregnant women and their 50 infants (one had triplets), were isolated and characterized, in order to determine the type of HIV-1 variants that are predominantly transmitted. All were enrolled in the prenatal AIDS Clinical Trials Group (ACTG) and received anti-retroviral therapy. Fifteen of the 50 infants (30%) were positive by V3 PCR suggesting that they harbored a copy of the HIV envelope gene. Three of 50 infants (6%) were HIV-1 culture and PCR positive, indicating active infection. HIV-positive cultures were obtained from 32 of the 48 mothers. Sixty two percent of the isolates (20/32) were macrophage-tropic and non-syncytium inducing, three percent (1/32) had dual tropism, and thirty four percent (11/32) were non-syncytium inducing and did not grow in macrophages. Phenotype and genotype of the HIV variants from the three infected infants revealed the presence of macrophage-tropic and non-syncytium-inducing strains. Genotype analysis of the HIV env V3 loop revealed the presence of specific amino acids that are predictive of CCR5 usage. Sequence analysis of the HIV pol gene from the three infected infants indicated that vertical transmission was not caused by the presence of antiviral resistance mutations. These results indicate that mothers undergoing antiretroviral treatment at different stages of the disease and with different viral loads transmit predominantly macrophage-tropic/non-syncytium inducing/CCR5 variants to their infants.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Complicações Infecciosas na Gravidez/virologia , Receptores CCR5/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Estudos de Coortes , DNA Viral/genética , Feminino , Variação Genética , Genótipo , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/transmissão , HIV-1/patogenicidade , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Fenótipo , Gravidez , Porto RicoRESUMO
The duration from initial infection with HIV-1 to CD4 lymphocyte depletion and progression to AIDS varies among infected individuals. Despite treatment with highly active antiretroviral therapy (HAART), patients still show different stages of disease progression. We examined the role of beta-chemokines and its receptor, CCR5 in HIV-1 infected children in order to define determinants of HIV progression among treated individuals. Population was divided in two groups: Group 1--Long Term Non Progressors (LTNP) includes 10 patients with B1-B2 CDC disease classification and with a less aggressive therapy (only 2 in HAART); Group 2--Rapid Progressors (RP) includes 9 patients with C3 disease classification. All the patients had a CCR5 wild type (wt) genotype indicating that they do not have the 32 base-pair deletion associated with slower progression. There was an increased production of MIP 1-beta in 8/10 LTNP but only in 4/9 Progressors (Paired t-test/Wilcoxon Sign test, p-value < 0.05). The change in the levels of MIP-1 beta after PHA stimulation was statistically significant in both groups. The levels of RANTES increased in LTNP and RP and the change of the levels after mitogen stimulation was statistically significant for both groups included. The production of RANTES and MIP-1 beta in response to stimulation between both groups was not statistically significant. The production of MIP-1 alpha was variable in both groups and the difference in the levels after mitogen stimulation between the groups was not statistically significant. These results suggest that beta-chemokines do not play an important role in HIV-1 progression in children undergoing HAART.