RESUMEN

BACKGROUND: The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy. METHODS: Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL. RESULTS: At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P < .001). CONCLUSIONS: Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10.

Asunto(s)

Infecciones por VIH , Infecciones Neumocócicas , Anticuerpos Antibacterianos/uso terapéutico , Femenino , VIH , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Polisacáridos , Embarazo , Streptococcus pneumoniae , Vacunación , Vacunas Conjugadas

RESUMEN

BACKGROUND: Pneumococcal vaccination is recommended in people with HIV, prioritizing PCV. We compared the immunogenicity of PCV-10 and PPV-23 administered antepartum or postpartum. METHODS: This double-blind study randomized 346 pregnant women with HIV on antiretrovirals to PCV-10, PPV-23, or placebo at 14-34 weeks gestational age. Women who received placebo antepartum were randomized at 24 weeks postpartum to PCV-10 or PPV-23. Antibodies against 7 serotypes common to both vaccines and 1 serotype only in PPV-23 were measured by ELISA/chemiluminescence; B- and T-cell responses to serotype 1 by FLUOROSPOT; and plasma cytokines/chemokines by chemiluminescence. RESULTS: Antibody responses were higher after postpartum versus antepartum vaccination. PCV-10 generated lower antibody levels than PPV-23 against 4 and higher against 1 of 7 common serotypes. Additional factors associated with high postvaccination antibody concentrations were high prevaccination antibody concentrations and CD4+ cells; low CD8+ cells and plasma HIV RNA; and several plasma cytokines/chemokines. Serotype 1 B- and T-cell memory did not increase after vaccination. CONCLUSIONS: Antepartum immunization generated suboptimal antibody responses, suggesting that postpartum booster doses may be beneficial and warrant further studies. Considering that PCV-10 and PPV-23 had similar immunogenicity, but PPV-23 covered more serotypes, use of PPV-23 may be prioritized in women with HIV on antiretroviral therapy. CLINICAL TRAILS REGISTRATION: NCT02717494.

Asunto(s)

Infecciones por VIH , Infecciones Neumocócicas , Anticuerpos Antibacterianos , Citocinas , Femenino , Infecciones por VIH/complicaciones , Humanos , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Polisacáridos , Periodo Posparto , Embarazo , Vacunación , Vacunas Conjugadas

RESUMEN

Pregnant women coinfected with the human immunodeficiency virus (HIV) and human gammaherpesvirus 8 (HHV-8) are at higher risk of Kaposi's sarcoma development, increased viral load, and vertical transmission of these viruses. A total of 131 pregnant women infected with HIV were examined for antibodies against HHV-8 latency-associated nuclear antigen (LANA) and lytic antigens using immunofluorescence assays. The presence of HHV-8 DNA was confirmed using real-time polymerase chain reaction (qPCR) and nested PCR. Overall, 0.8% (1/131) of the patients contained antibodies to HHV-8 LANA and lytic antigens, and no HHV-8 DNA was detected. This study, including a small population of HIV-infected pregnant women in Brazil, indicates a low prevalence of HHV-8 seropositivity and absence of active infection in this group. However, a potential role of HHV-8 in the increased transmission and pathogenic activity of HIV in pregnant women is suggested. Attention should be given to the emergence of HHV-8 infection in this population group in order to avoid comorbidities and transmission of HIV.

Asunto(s)

Infecciones por VIH , Herpesvirus Humano 8 , Sarcoma de Kaposi , Anticuerpos Antivirales , Brasil/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Embarazo , Mujeres Embarazadas , Prevalencia

Asunto(s)

ADN Viral/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Tamizaje Masivo/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Manejo de Especímenes/métodos , Adolescente , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Coinfección/epidemiología , Estudios Transversales , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Herpesvirus Humano 2/genética , Humanos , Tamizaje Masivo/estadística & datos numéricos , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Autocuidado

RESUMEN

The anogenital prevalence of sexually transmitted infections (STIs) and the use of cervico-vaginal self-collected vs. clinician-collected samples were evaluated for the diagnosis of human immunodeficiency virus (HIV)-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil. We recruited 153 women for a cross-sectional study (112 HIV-uninfected and 41 HIV-infected) who sought health services. Anal and cervical scrapings and cervico-vaginal self-collection samples were collected. Real-time polymerase chain reaction methods were used for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium. A syphilis test was also performed. Risk factors for STIs were identified by multivariate analysis. The overall prevalence of STIs was 30.4% (34/112) in HIV-uninfected women and 24.4% (10/41) in HIV-infected women. Anogenital Chlamydia trachomatis infection was the most prevalent in both groups of women (20.5% vs 19.5%). There was significant agreement for each STI between self-collected and clinician-collected samples: 91.7%, kappa 0.67, 95% confidence interval (CI) 0.49-0.85 for Chlamydia trachomatis; 99.2%, kappa 0.85, 95% CI 0.57-1.00 for Neisseria gonorrhoeae; 97.7%, kappa 0.39, 95% CI -0.16-0.94 for Trichomonas vaginalis; and 94.7%, kappa 0.51, 95% CI 0.20-0.82 for Mycoplasma genitalium. Women with human papillomavirus had coinfection or multiple infections with other STIs. Risk factors for STIs were being ≤ 25 years old, being employed or a student, reporting a history of STI and having a positive HPV test. A high prevalence of STIs in women in the Tapajós region was found. Cervico-vaginal self-collection is a useful tool for STI screening and can be used in prevention control programs in low-resource settings, such as in northern Brazil.

Asunto(s)

Infecciones por Chlamydia , Coinfección , Gonorrea , Infecciones por VIH , Infecciones por Mycoplasma , Infecciones por Papillomavirus , Manejo de Especímenes , Vaginitis por Trichomonas , Adolescente , Adulto , Brasil/epidemiología , Cuello del Útero/microbiología , Cuello del Útero/virología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/microbiología , Infecciones por Chlamydia/virología , Chlamydia trachomatis , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , Estudios Transversales , Femenino , Gonorrea/epidemiología , Gonorrea/microbiología , Gonorrea/virología , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Infecciones por VIH/virología , VIH-1 , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/virología , Mycoplasma genitalium , Neisseria gonorrhoeae , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/microbiología , Infecciones por Papillomavirus/virología , Vaginitis por Trichomonas/epidemiología , Vaginitis por Trichomonas/microbiología , Vaginitis por Trichomonas/virología , Trichomonas vaginalis

RESUMEN

OBJECTIVE: We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil. METHODS: Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, n = 112 and HIV-infected, n = 41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses. RESULTS: The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% confidence interval [CI], 0.65-0.87) and hrHPV (79.7%, 0.56, 95% CI, 0.41-0.71) between self-collected and clinician-collected samples. The most prevalent hrHPV types were HPV16 and HPV18 in HIV-uninfected and HPV16, HPV51 and HPV59 in HIV-infected women. HIV-infected women with hrHPV infection had multiple hrHPV infections (p = 0.005) and lower CD4 count (p = 0.018). Risk factors for hrHPV infection included being HIV-infected and having five or more sexual partners. CONCLUSIONS: CVSC had high acceptability and high prevalence of hrHPV types in women living in the Tapajós region, Amazon, Brazil.

Asunto(s)

Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Anciano , Brasil/epidemiología , Recuento de Linfocito CD4 , Cuello del Útero/patología , Cuello del Útero/virología , Estudios Transversales , ADN Viral/aislamiento & purificación , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Prevalencia , Factores de Riesgo , Manejo de Especímenes/métodos , Manejo de Especímenes/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Vagina/patología , Vagina/virología , Adulto Joven

RESUMEN

Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.

Asunto(s)

Farmacorresistencia Viral , Variación Genética , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Complicaciones Infecciosas del Embarazo/virología , Adolescente , Adulto , Fármacos Anti-VIH/farmacología , Brasil/epidemiología , Femenino , Genotipo , Infecciones por VIH/epidemiología , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/aislamiento & purificación , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Recombinación Genética , Adulto Joven

RESUMEN

The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV+ individuals in Brazil. The sequences were obtained by overlapping PCR amplifications followed by direct sequencing. Recombination profiles were determined by phylogenetic and bootscaning analyses. The evolutionary history was estimated by a Bayesian coalescent-based method using datasets representing the gag, pol and env gene fragments. Six of the 10 samples isolated in Rio de Janeiro showed a CRF45_cpx-like pattern throughout the sequenced genome. The remaining were classified as second-generation recombinants, showing the mosaic patterns: CRF45_cpx/B/D/F1/U, CRF45_cpx/B/F1/U, CRF45_cpx/B/U and CRF45_cpx/F1. All Brazilian CRF45_cpx sequences, except one, formed a monophyletic clade (CRF45-BR), which seems to be the result of a single introduction event that has spread to the Rio de Janeiro, São Paulo and Minas Gerais states and is related to sequences from Argentina, Italy and Belgium. The Bayesian analyses pointed out quite consistent onset dates for CRF45-BR clade (~1984: 1976-1996) in the three gene datasets. These results indicate that the CRF45-BR clade has been circulating in the Southeastern Brazilian region for about 30years, although its presence was not detected until recently due to its very low prevalence. This reinforces the relevance of large-scale molecular surveillance data to identify the emergence of new HIV variants and their impact on local epidemics.

Asunto(s)

Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Teorema de Bayes , Brasil/epidemiología , Trazado de Contacto , Femenino , Genoma Viral/genética , Infecciones por VIH/epidemiología , Humanos , Masculino , Filogenia , Embarazo , ARN Viral/análisis , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ADN

RESUMEN

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Asunto(s)

Sistema Nervioso Central/anomalías , Muerte Fetal , Retardo del Crecimiento Fetal/virología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/complicaciones , Virus Zika/aislamiento & purificación , Adolescente , Adulto , Encéfalo/anomalías , Brasil/epidemiología , Sistema Nervioso Central/embriología , Femenino , Muerte Fetal/etiología , Retardo del Crecimiento Fetal/epidemiología , Feto/anomalías , Edad Gestacional , Humanos , Persona de Mediana Edad , Embarazo , Nacimiento Prematuro/epidemiología , Ultrasonografía Prenatal , Adulto Joven

RESUMEN

HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from São Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years.

Asunto(s)

Genotipo , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Adulto , África/epidemiología , Brasil/epidemiología , Análisis por Conglomerados , Biología Computacional , Femenino , Infecciones por VIH/epidemiología , VIH-1/aislamiento & purificación , Humanos , Masculino , Epidemiología Molecular , Filogeografía , Embarazo

RESUMEN

BACKGROUND: Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. METHODS: The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. FINDINGS: 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373-522) cells per µL in patients assigned to the early treatment group and 428 (357-522) cells per µL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197-249) cells per µL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52-1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43-0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28-0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5-27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5-32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. INTERPRETATION: Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment. FUNDING: US National Institute of Allergy and Infectious Diseases.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antirretrovirales/administración & dosificación , VIH-1 , Tuberculosis Pulmonar/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Recuento de Linfocito CD4 , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Fallo Renal Crónico/complicaciones , Hepatopatías/complicaciones , Masculino , Neoplasias/complicaciones , Modelos de Riesgos Proporcionales , Factores de Tiempo , Adulto Joven

RESUMEN

The remarkable viral diversity remains a big challenge to the development of HIV vaccines and optimal therapy worldwide. In the latest years, as a consequence of the large expansion of highly active antiretroviral therapy (HAART) availability worldwide, an increase in transmitted drug resistance mutations (TDRM) has been observed, varying according the region. This study assessed HIV-1 diversity and TDRM profile over time among newly HIV-1 diagnosed individuals from Rio de Janeiro, Brazil. Blood samples were collected from individuals seeking HIV diagnosis in four voluntary counseling and testing (VCTs) sites located in the Rio de Janeiro Metropolitan Area, in 2005-2007. Recent (RS) and long-term (LTS) HIV-1 seroconverters were distinguished using BED-CEIA. Pol viral sequences were obtained for 102 LTS identified in 2005 and 144 RS from 2005-2007. HIV-1 subtype and pol recombinant genomes were determined using Rega HIV-1 Subtyping Tool and by phylogenetic inferences and bootscanning analyses. Surveillance of HIV-1 TDRM to protease and reverse transcriptase inhibitors were performed according to the Calibrated Population Resistance (CPR) Tool 6.0. Overall, subtype B remains the most prevalent in Rio de Janeiro in both LTS and RS HIV-1 infected individuals. An increased proportion of recombinant samples was detected over time, especially in RS heterosexual men, due to the emergence of CRF02_AG and URF samples bearing a subtype K fragment. The prevalence of HIV-1 samples carrying TDRM was high and similar between LTS and RS (15.7% vs 14.6%) or age (<25yo 17.9% vs >25yo 16.6%) along the study period. The high resistance levels detected in both populations are of concern, especially considering the dynamics of HIV-1 diversity over time. Our results suggest that the incorporation of resistance testing prior to HAART initiation should be highly considered, as well as permanent surveillance, aiming to carefully monitoring HIV-1 diversity, with focus on CRF/URF emergence and putative transmission.

Asunto(s)

Farmacorresistencia Viral/genética , Infecciones por VIH/diagnóstico , Infecciones por VIH/genética , VIH-1/genética , Mutación/genética , Adolescente , Adulto , Brasil , Consejo , Femenino , Genotipo , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , Adulto Joven

RESUMEN

BACKGROUND: Maternal human immunodeficiency virus (HIV) coinfection has been associated with increased hepatitis C virus (HCV) mother-to-child transmission (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV disease would not have increased HCV MTCT. METHODS: The NISDI Perinatal and LILAC cohorts enrolled HIV-infected pregnant women and their infants in Latin America and the Caribbean. This substudy evaluated the HCV infection status of mothers at participating sites and their live born, singleton infants who had a 6-month postnatal visit by December 31, 2008. Mothers who were anti-HCV-positive, or who had CD4 counts (cells/mm(3)) <200 with detectable HCV RNA, were considered HCV-infected. All HCV-infected women were tested for HCV RNA. Infants with HCV RNA were considered HCV-infected. RESULTS: Of 1042 enrolled women, 739 (71%) mother-infant pairs met the inclusion criteria. Of the 739 women, 67 (9%) were anti-HCV-positive and 672 anti-HCV-negative [68 (10%) with CD4 counts <200; of these, 3 (4.4%) were HCV RNA-positive]. Therefore, our study population comprised 70 HCV-infected (47 with HCV RNA) and 669 HCV-uninfected women (and their infants). Factors associated with maternal HCV infection included unemployment (odds ratio [OR] = 2.58); tobacco (OR = 1.73) or marijuana (OR = 3.88) use during pregnancy; enrollment HIV viral load ([VL] copies/mL) ≥10 000 (OR = 2.27); HIV clinical disease stage C (OR = 2.12); and abnormal alanine aminotransferase (OR = 4.24) or aspartate aminotransferase (OR = 11.98). Four of 47 infants (8.5%) born to HCV-viremic women were HCV-infected, and all 4 mothers had HIV VL <1000 at hospital discharge after delivery. CONCLUSIONS: HCV MTCT among HIV/HCV-coinfected women with well-controlled HIV disease may be lower than reported in other coinfected populations. Studies with longer infant follow-up are needed.

RESUMEN

Transmission of drug-resistant HIV-1 strains has been gaining attention and is becoming a growing problem throughout the world. The aim of this study was to determine the prevalence of transmitted drug resistance mutations (TDRM) among antiretroviral (ARV)-naive HIV-infected pregnant women in Rio de Janeiro, Brazil. ARV-naive pregnant women were recruited at Hospital Geral de Nova Iguacu (HGNI), Rio de Janeiro, from 2005 to 2008. HIV genotyping was carried out using ViroSeq (Abbott v. 2.0). TDRM were detected using the Calibrated Population Resistance Tool-CPR v. 6.0.The prevalence of mutations associated with resistance in the protease and reverse transcriptase regions of the HIV genome were assessed in samples collected prior to initiation of ARV prophylaxis or treatment. Among 238 eligible specimens that were collected, 197 samples were successfully amplified using reverse transcription polymerase chain reaction. Eighty-one percent of women were infected with HIV subtype B, 10% with subtype F1 viruses, 1.0% with subtype C virus, and 8.0% with recombinant forms of the virus. The prevalence of HIV TDRM was 5.6% for nucleoside reverse transcriptase inhibitors, 2.0% for nonnucleoside reverse transcriptase inhibitors, and 3.0% for protease inhibitors. The overall prevalence of any drug resistance was 10.7%. There were no multiclass resistant strains identified in the analyzed samples. The prevalence of HIV TDRM among the pregnant women in our cohort was moderate. Resistance testing should be encouraged in Rio de Janeiro, among other locations, for all HIV-infected pregnant women prior to prevention of mother-to-child transmission of HIV.

Asunto(s)

Farmacorresistencia Viral/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Mutación , Complicaciones Infecciosas del Embarazo/virología , Adulto , Brasil , Estudios de Cohortes , Femenino , Genoma Viral , Infecciones por VIH/transmisión , Humanos , Tasa de Mutación , Embarazo , Estudios Prospectivos , Adulto Joven

RESUMEN

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/epidemiología , Fármacos Anti-VIH/administración & dosificación , Lactancia Materna/estadística & datos numéricos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Cumplimiento de la Medicación/estadística & datos numéricos , Periodo Posparto , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/psicología , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Lactancia Materna/psicología , Recuento de Linfocito CD4 , Femenino , Humanos , Recién Nacido , América Latina/epidemiología , Cumplimiento de la Medicación/psicología , Embarazo , Atención Prenatal , Estudios Prospectivos , Fumar/epidemiología , Carga Viral

RESUMEN

BACKGROUND: Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. METHODS: Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to ≤200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models. RESULTS: A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline ≥500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02). CONCLUSIONS: In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.

Asunto(s)

Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Brasil , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virología , Resultado del Tratamiento , Carga Viral , Adulto Joven

RESUMEN

BACKGROUND: BED-EIA HIV-1 Incidence Test (BED-CEIA) has been described as a tool to discriminate recent (RS) from long-term (LTS) seroconversion of HIV-1 infection, contributing to a better understanding of the dynamics of the HIV/AIDS epidemic over time. This study determined the prevalence, estimated incidence and HIV-1 subtype infection among individuals seeking testing in Voluntary Counseling and Testing centers (VCTs) from Rio de Janeiro, Brazil. METHODS: Demographics and behavioral data were obtained from 434 individuals, diagnosed as HIV-positive among 9,008 volunteers screened from November 2004 to October 2005 in three VCTs located in the Rio de Janeiro Metropolitan area, Brazil. BED-CEIA protocol was performed to identify RS. DNA samples from RS and a subset of LTS (under a proportion of 1:2) were selected for gp120 C2-V3 and pol (protease and reverse transcriptase) regions genomic sequencing. RESULTS: Overall HIV-1 prevalence was 4.8%. Sixty-one of 434 seropositive individuals were classified as RS, corresponding to an incidence rate of 1.68%/year (95%CI 1.26% -2.10%). Estimated incidence between Men Who Have Sex with Men (MSM) was 11 times higher than among heterosexual men and 55% of the new cases were identified in volunteers aged 25-40 years. A similar distribution of different HIV-1 subtypes was found among RS and LTS. CONCLUSIONS: Our data suggest that prevention for MSM remains a challenge and efforts focusing on prevention targeting this population should be prioritized. No significant changes in HIV-1 subtypes were observed among the RS and LTS subgroups. One case of HIV-1 AUK (pol)/A (env) recombinant genome was detected for the first time in Brazil.

Asunto(s)

Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , VIH-1/clasificación , VIH-1/genética , Adulto , Brasil/epidemiología , ADN Viral/química , ADN Viral/genética , Femenino , Genotipo , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Experimentación Humana , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Secuencia de ADN , Población Urbana , Adulto Joven , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética

RESUMEN

OBJECTIVE: To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States. METHODS: We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death. RESULTS: A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value = 0.95) after adjusting for CD4 T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4 T cell count less than or equal to 50 cells/microl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die. CONCLUSION: Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country.

Asunto(s)

Terapia Antirretroviral Altamente Activa/mortalidad , Infecciones por VIH/mortalidad , Adulto , Brasil/epidemiología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Causas de Muerte , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Estados Unidos/epidemiología , Carga Viral

RESUMEN

An extremely rare subset of patients infected with HIV-1 designated as "non-progressing elite controllers" appears to be able to maintain stable CD4(+) T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50-80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4(+), CD8(+)), immune activation markers (HLA-DR(+), CD38(+), Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8(+) T-cell counts and beta2-M levels above normal ranges and developed a low but "mature" (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV-1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity.

Asunto(s)

Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , Sobrevivientes de VIH a Largo Plazo , VIH-1/inmunología , Adulto , Afinidad de Anticuerpos , Formación de Anticuerpos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Microglobulina beta-2/sangre

RESUMEN

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease in developing countries, including Brazil, and is especially prevalent among men who have sex with men (MSM). HSV-2 infection represents a risk factor for the acquisition and transmission of other sexually transmitted diseases. The goal of the present cross-sectional study was to estimate HSV-2 seroprevalence and to determine the factors associated with HSV-2 seropositivity in HIV-negative high-risk MSM from Rio de Janeiro, Brazil. METHODS: Stored sera were tested to estimate HSV-2 seroprevalence, while socio-demographic and sexual behavior data were used to measure associations between risk factors and HSV-2 seropositivity. Using the Poisson regression model with robust variance, prevalence ratios (PR) were used to estimate de degree of association between risk factors and HSV-2 seropositivity in bivariate and multivariate analyses. RESULTS: Seroprevalence of HSV-2 was of 45.7% (184 out of 403). Factors independently associated with HSV-2 seroprevalence in the multivariate model were: older age (>or= 26 years, PR: 1.41 95% Confidence Interval: 1.11-1.78), non-white race (PR: 1.32 95%CI: 1.06-1.64), positive serology for syphilis (PR: 1.65 95%CI: 1.33-2.05), positive serology for hepatitis B (PR: 1.25 95%CI: 0.99-1.57), stable male partner in the past 6 months (PR: 1.42 95%CI: 1.12-1.79), and unprotected anal sex with a stable female partner (PR: 1.46 95%CI: 1.05-2.04) in the 6 months preceding the cross-sectional assessment. CONCLUSION: The present study made evident a high prevalence of HSV-2 infection in a sample of HIV-negative high-risk MSM from Rio de Janeiro. This finding indicates the need and urgency for implementing integrated programs for the prevention of HSV-2 and other sexually transmitted diseases, and, in particular, programs targeting high-risk MSM.

Asunto(s)

Seronegatividad para VIH , Herpes Genital/epidemiología , Herpesvirus Humano 2 , Homosexualidad Masculina , Adolescente , Adulto , Factores de Edad , Brasil/epidemiología , Estudios Transversales , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Herpes Genital/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Análisis de Regresión , Factores de Riesgo , Estudios Seroepidemiológicos , Sífilis/complicaciones , Sífilis/epidemiología , Adulto Joven