RESUMO
This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica.
Assuntos
Farmacorresistência Viral , Genes pol , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Variação Genética , HIV-1/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Jamaica , Dados de Sequência Molecular , Mutação , Filogenia , Análise de Sequência de DNA , Falha de TratamentoRESUMO
BACKGROUND: In Trinidad and the wider Caribbean, subtype B Human Immunodeficiency Virus-type 1 (HIV-1B) overwhelmingly accounts for HIV infection among heterosexuals; this contrasts with the association of HIV-1B with homosexual transmission and injecting drug use globally. The HIV envelope contains genetic determinants of cell tropism and evasion from immune attack. In this study we investigate the genetic properties of the env V1-C4 of HIV-1B soon after transmission to Trinidadian heterosexuals. This will reveal distinctive genetic features of the strains that cause the HIV-1B epidemic in Trinidad and generate insights to better understand their properties. METHODOLOGY/PRINCIPAL FINDINGS: Quasispecies sampling was performed on the env V1-C4 of HIV-1B strains soon after transmission to heterosexual Trinidadians in a cohort of seroconverters. Phylogenetic relationships were determined for these quasispecies and the length and number of asparagine (N) linked glycosylation sites (NLGS) in their variable loops compared to that for HIV-1B globally. Signature amino acids within the constant domains of the env V1-C4 were identified for heterosexually transmitted HIV-1B from Trinidad relative to HIV-1B globally. HIV-1B obtained from Trinidadian heterosexuals soon after seroconversion had significantly longer V2 loops with one more glycosylation site, shorter V3 loops and no significant difference in V1 or V4 when compared to HIV-1B obtained soon after seroconversion from infected individuals in the rest of the world. HIV-1B soon after seroconversion and during chronic infection of Trinidadians was not significantly different, suggesting that distinctly long V2 loops are characteristic of HIV-1B in Trinidad. A threonine deletion at position 319 (T319-) along with the substitutions R315K and S440R were found to be distinctly associated with HIV-1B from Trinidad compared to HIV-1B globally. CONCLUSIONS: This finding of distinctive genetic features that are characteristic of HIV-1B strains from Trinidad is consistent with the Trinidad epidemic being established by a founder strain or closely related founder strains of HIV-1B.
Assuntos
Infecções por HIV/virologia , HIV-1/química , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/virologia , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Estudos de Coortes , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Filogenia , Fatores de Risco , Homologia de Sequência de Aminoácidos , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/transmissão , Trinidad e Tobago/epidemiologiaRESUMO
OBJECTIVE: We investigated the hypothesis that partner-specific characteristics are important to improve an individual's risk characterization. DESIGN: It has been shown that the egocentric network structure is important to establish a person's risk for infection. METHODS: The study was cross-sectional in its design and enrolled 1231 volunteers at one HIV testing site in Rio de Janeiro, Brazil, and applied an adapted ego-network questionnaire. Each individual was interviewed about their own risk factors and those related to up to 10 sex partners. We used the dyadic data analysis method in which each relationship forms a record. Two receiver operator characteristic curves were generated, and the ability to correctly predict volunteers' HIV serostatus based on a model with characteristics of volunteers and sex partners and another with only volunteers' characteristics was evaluated. RESULTS: Partner-related variables were associated with HIV serostatus both for men and women. The model with volunteer/sex partners' characteristics performed better in discriminating between HIV-positive and negative volunteers only for men but not for women. The c statistic for men volunteers was 0.82 [95% confidence interval (CI) 0.77-0.87] for the volunteer alone model and 0.88 (95% CI 0.86-0.91) for the combined model (P = 0.03). The values for women were 0.75 (95% CI 0.65-0.86) and 0.78 (95% CI 0.71-0.85), respectively (P = 0.71). CONCLUSION: Ego-network theory-based approaches provide additional information for characterizing risk for HIV infection among men.
Assuntos
Soronegatividade para HIV , Soropositividade para HIV/transmissão , Parceiros Sexuais/classificação , Inquéritos e Questionários , Adulto , Brasil/epidemiologia , Intervalos de Confiança , Estudos Transversais , Feminino , Soropositividade para HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/classificação , Sexo Seguro/psicologia , Fatores Sexuais , Parceiros Sexuais/psicologiaRESUMO
BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.
Assuntos
Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Sequência de Bases , Primers do DNA , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Índias Ocidentais/epidemiologiaRESUMO
BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.
Assuntos
Humanos , HIV-1 , Genoma Humano , Trinidad e Tobago , Haiti , República Dominicana , Jamaica , Região do CaribeRESUMO
OBJECTIVE: To evaluate supplementary cueing as a technique to increase recall of sex partners in the year before the interview. GOAL: Recall of partners beyond those freely recalled. STUDY DESIGN: We asked volunteers at a clinic in Brazil to freely recall all regular and casual sex partners in the year before the interview. Then, we used a name generator developed by Brewer et al. in the United States, in which volunteers were prompted with 4 types of cues: location, alphabetic, social role, and network. We calculated different measures to evaluate the technique and analyzed the associations between reporting any additional partner and demographic characteristics. RESULTS: Among volunteers reporting 2 or more sexual partners (n = 590), 41 (7%) recalled 1 or more additional partners by using the supplementary technique, with 105 partners of 2090 (5%) recalled only after using the cues. For volunteers reporting 4 or more sexual partners (n = 193), 34 (18%) recalled 1 or more additional partners by using the supplementary technique, and 98 of 1177 (8%) of their sexual partners were recalled after using the cues. Men were less likely than women to report sex partners after prompting with the social role cues (OR 0.09), and overall the combined techniques were slightly less effective for older individuals (OR 0.95). CONCLUSION: The cue technique can improve sexual partners' recall in cultural contexts different than the United States, mainly for individuals already reporting several partners before the cue.
Assuntos
Busca de Comunicante , Rememoração Mental , Trabalho Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Sexualmente Transmissíveis/etiologiaRESUMO
OBJECTIVE: Human T-cell lymphotropic virus type I (HTLV-I) infection in childhood is believed to play an important role in risk for adult T-cell leukemia/lymphoma. Although HTLV-I is known to be associated with infective dermatitis in childhood, other HTLV-I-associated morbidity in children has not been well studied. We sought to determine the HTLV-I-associated health effects in Jamaican children. METHODS: We compared incidence rates of several health outcomes in 28 HTLV-I-infected and 280 uninfected children clinically followed from age 6 weeks to a maximum of 10 years. Cox proportional hazards regression analysis was used to analyze these prospectively collected data, adjusting for confounding effects of other variables as necessary. RESULTS: HTLV-I-infected children had significantly higher incidence rates of seborrheic dermatitis (rate ratio [RR] = 4.8, 95% confidence interval [CI] = 1.9-12.5), eczema (RR = 3.1, CI = 1.2-7.9) and persistent hyperreflexia (RR = 3.7, CI = 1.6-8.2). Additionally, HTLV-I infected children had increased rates of severe anemia (RR = 2.5, CI = 0.8-7.9) and abnormal lymphocytes (RR = 2.4, CI = 0.8-7.6) that were of borderline statistical significance. CONCLUSIONS: Our study suggests that HTLV-I-associated skin diseases of childhood may include seborrheic dermatitis and eczema. Additionally, these data suggest that persistent hyperreflexia of the lower limbs may be an early sign of HTLV-I-associated neurologic involvement in children. Expansion and continued clinical observation of this cohort would be valuable.
Assuntos
Anemia/etiologia , Dermatite Seborreica/etiologia , Eczema/etiologia , Infecções por HTLV-I/complicações , Reflexo Anormal , Anemia/epidemiologia , Aleitamento Materno , Estudos de Coortes , Dermatite Seborreica/epidemiologia , Eczema/epidemiologia , Infecções por HTLV-I/fisiopatologia , Incidência , Jamaica/epidemiologia , Exame Neurológico , Modelos de Riscos ProporcionaisRESUMO
The VIDAS HIV DUO Ultra, a fourth-generation immunoassay under development for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 and HIV-2, was evaluated. The enzyme-linked fluorescence immunoassay, performed on the automated VIDAS instrument, is claimed to detect early and established HIV infection. The assay was challenged with a total of 2,847 samples that included 74 members of 10 seroconversion panels, 9 p24 antigen-only-reactive members of a panel of group M clades, 503 consecutively collected samples from individuals seeking care in the University of Maryland Medical System, 1,010 samples from U.S. blood donors, 1,141 samples from patients in a high-incidence population in Trinidad, 83 samples from a clinic for sexually transmitted diseases in the Bahamas, 10 confirmed HIV-1 group O samples, and 16 confirmed HIV-2 samples from the Cote d'Ivoire. Reference tests were U.S. Food and Drug Administration-licensed HIV antibody screening, p24 antigen tests, HIV confirmatory assays, and the Roche Diagnostics Amplicor HIV-1 Monitor. The VIDAS HIV DUO Ultra demonstrated 100% sensitivity and 99.5% specificity overall, with a 99.7% specificity in low-risk individuals. The analytical sensitivity, as assessed by seroconversion panels and p24 antigen in samples, was equivalent to the sensitivity of the reference assays used to characterize these panels. The VIDAS HIV DUO Ultra is accurate, offers potential advantages over conventional HIV testing for time and cost savings, has walk-away capability, and correctly identifies both early and established HIV infections.
Assuntos
Humanos , Masculino , Feminino , Research Support, Non-U.S. Gov't , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Anti-HIV/sangue , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/isolamento & purificação , HIV-2/imunologia , HIV-2/isolamento & purificação , Sensibilidade e Especificidade , Trinidad e TobagoRESUMO
Mother-to-child transmission of human T-cell lymphotrophic virus type 1 (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the post-natal period. Most infant infections are not identifiable until 12-18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was observed in 100 percent of children at 24 months of age and 73 percent of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50 percent of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P=0.72). PCR Tests support a median time to infection that is similar to that estimated by whole virus Western blot. (AU)