Reformulation of a thermostable broadly protective recombinant vaccine against human papilloma virus

The causal relationship between Human Papilloma Virus (HPV) infection and cervical cancer has motivated the development, and further improvement, of prophylactic vaccines against this virus. 70% of cervical cancers, 80% of which in low-resources countries, are associated to HPV16 and HPV18 infection, with 13 additional HPV types, classified as high-risk, responsible for the remaining 30% of tumors. Current vaccines, Cervarix® (GlaxoSmithKline) and Gardasil®(Merk), are based on virus-like particles (VLP) obtained by self-assembly of the major capsid protein L1. Despite their undisputable immunogenicity and safety, the fact that protection afforded by these vaccines is largely limited to the cognate serotypes included in the vaccine (HPV 16 and 18, plus five additional viral types incorporated into a newly licensed nonavalent vaccine) along with high production costs and reduced thermal stability, are pushing the development of 2nd generation HPV vaccines based on minor capsid protein L2. The increase in protection broadness afforded by the use of L2 cross-neutralizing epitopes, plus a marked reduction of production costs due to bacterial expression of the antigens and a considerable increase in thermal stability could strongly enhance vaccine distribution and usage in low-resource countries. Previous studies from our group identified three tandem repeats of the L2 aa. 20-38 peptide as a strongly immunogenic epitope if exposed on the scaffold protein thioredoxin (Trx). The aim of this thesis work is the improvement of the Trx-L2 vaccine formulation with regard to cross-protection and thermostability, in order to identify an antigen suitable for a phase I clinical trial. By testing Trx from different microorganisms, we selected P. furiosus thioredoxin (PfTrx) as the optimal scaffold because of its sustained peptide epitope constraining capacity and striking thermal stability (24 hours at 100°C). Alternative production systems, such as secretory Trx-L2 expression in the yeast P. pastoris, have also been set-up and evaluated as possible means to further increase production yields, with a concomitant reduction of production costs. Limitations in immune-responsiveness caused by MHC class II polymorphisms –as observed, for example, in different mouse strains- have been overcome by introducing promiscuous T-helper (Th) epitopes, e.g., PADRE (Pan DR Epitope), at both ends of PfTrx. This allowed us to obtain fairly strong immune responses even in mice (C57BL/6) normally unresponsive to the basic Trx-L2 vaccine. Cross-protection was not increased, however. I thus designed, produced and tested a novel multi-epitope formulation consisting of 8 and 11 L2(20-38) epitopes derived from different HPV types, tandemly joined into a single thioredoxin molecule (“concatemers”). To try to further increase immunogenicity, I also fused our 8X and 11X PfTrx-L2 concatemers to the N-terminus of an engineered complement-binding protein (C4bp), capable to spontaneously assemble into ordered hepatmeric structures, previously validated as a molecular adjuvant. Fusion to C4bp indeed improved antigen presentation, with a fairly significant increase in both immunogenicity and cross-protection. Another important issue I addressed, is the reduction of vaccine doses/treatment, which can be achieved by increasing immunogenicity, while also allowing for a delayed release of the antigen. I obtained preliminary, yet quite encouraging results in this direction with the use of a novel, solid-phase vaccine formulation, consisting of the basic PfTrx-L2 vaccine and its C4bp fusion derivative adsorbed to mesoporus silica-rods (MSR).

Substance Use and Sexual Risk Behaviors among Adolescent Detainees

During the past two decades there has been much research conducted on the relationship between the risky sexual behavior practices and substance use among U.S. adolescents. This body of research has documented the fact that substance use and not using condoms are the most important indicators associated with the risk of becoming infected with sexually transmitted diseases (STD) both among adolescents and adults (Florida Department of Public Health, 2004; Malow, Devieux, Jennings, & Lucenko, 2001; McCoy & Inciardi, 1995). Data from those reports and studies indicate that adolescents and adults who use a condom regularly and appropriately are 20 times less likely to contract an STD than those who do not (Pinkerton & Abramson, 1997). However, less empirical evidence exists about the factors that influence adolescent use of condoms, particularly among adolescents who are detained due to their criminal lifestyle. Researchers have found both a high prevalence of STD in addition to early onset of sexual activity without protection among some adolescent groups such as the detainees (D'angelo & DiClemente, 1996) and that adolescents tend to underestimate their risks of acquiring the human immunodeficiency virus (HIV) (Magura, Shapiro, & Kang, 1994). Many adolescents will experiment with alcohol and other drugs. This behavior may compromise their judgment and increase their chances of engaging in risky sex (Rotheram-Borus, 2000). Hence the need for research that investigates the influence that substance use, risky sexual attitudes, knowledge about the transmission of HIV, and both peer and parental approval of condom use have on the use of condoms among both female and male adolescent detainees. Lastly, it is important for additional research to be conducted because adolescent detainees have been identified as being at high risk of becoming infected with an STD (Malow, Rosemberg, & Devieux, 2006). The purpose of this study was to examine the relationship among adolescent substance use, gender, sexual risk attitude, attitude about personal use of condoms, knowledge associated with the transmission of HIV, peer and family approval of condom use, history of sexually transmitted diseases (STD) and the level of condom use in a sample of adolescents housed in a correctional institution. Further details of the explanatory variables, the control variables and their expected relationships can be found in the review of the Literature in Chapter 2. Also, more information about the separate analysis of the research questions is detailed in the Methods section in Chapter 3. Based on the literature detailed in Chapter 2 (e.g., Malow et al., 2006), the current study’s researcher anticipated that adolescents’ higher levels of illicit drug use would be related to higher levels of sexual risk behaviors, as measured by lower levels of condom use, than their counterparts who used no drugs. Similarly, it was hypothesized that positive attitudes toward condom use and higher levels of HIV risk knowledge would be associated with a lower level of risky sexual behaviors along with a higher level of condom use skill. It was further hypothesized that the level of approval perceived from parents and peers regarding condom use was going to be related to adolescents’ safe sex behavior (i.e., condom use). Therefore, it was expected that participants’ perception of a high level of approval to use condoms from peers and parents would be a statistically significant variable in helping explain the condom use within this sample of adolescent detainees.

Human herpes virus-6 induced changes in the expression and activity of the E2F family transcription factors in human cells

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.

OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.

Human herpes virus-6 induced changes in the expression and activity of the E2F family transcription factors in human cells

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Transient hyperglycemia in patients with tuberculosis in Tanzania: implications for diabetes screening algorithms.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. METHODS: Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. RESULTS: At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). CONCLUSIONS: Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome.

Review: Head and neck squamous cell carcinoma in sub-Saharan Africa

Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed. Results Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare. Conclusions The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+ T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy.

Single-nucleotide polymorphism in two representative multidrug-resistant Mycobacterium bovis isolates collected from patients in a Spanish hospital harboring a human infection outbreak

Mycobacterium bovis is the etiological agent of tuberculosis in domestic and wild animals. Its involvement as a human pathogen has been highlighted again with the recent descriptions of transmission through dairy products (18), reactivation or primary infection in human immunodeficiency virus-infected patients (5), and association with meat industry workers, animal keepers, or hunters (3). Strains resistant to antituberculous drugs (M. bovis is naturally resistant to pyrazinamide) pose an additional risk (2). Several studies have demonstrated that mutations in target genes are associated with resistance to antituberculous drugs (4, 7, 10, 11, 16). However, most of them have been developed in Mycobacterium tuberculosis strains and limited data are available regarding M. bovis isolates. The aim of this study was to characterize by sequencing the main genes involved in antibiotic resistance in two multidrug-resistant (MDR) M. bovis isolates in a human outbreak detected in a hospital in Madrid that subsequently spread to several countries (5, 6, 15). The isolates were resistant to 11 drugs, but only their rpoB and katG genes have been analyzed so far (1, 14). We studied the first (93/R1) and last (95/R4) M. bovis isolates of this nosocomial outbreak, characterized by spoligotyping as SB0426 (hexacode 63-5F-5E-7F-FF-60 in the database at www.mbovis.org) (1, 13). Several genes involved in resistance to isoniazid (katG, ahpC, inhA, and the oxyR-ahpC intergenic region), rifampin (rpoB), streptomycin (rrs, rpsL), ethambutol (embB), and quinolones (gyrA) were studied. These genes, or fragments of genes, were amplified and sequenced as previously described (12). The sequence analysis revealed polymorphisms in five (ahpC, rpoB, rpsL, embB, and gyrA) out of nine analyzed genes (Table 1). Nucleotide substitutions in four genes cause a change in the encoded amino acid. Two additional synonymous mutations in ahpC and rpsL differentiated the first and last isolates from the outbreak.

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan

Modelo predictivo para uso del condón y consumo de alcohol como conductas de riesgo relacionadas con el contagio de VIH/SIDA en trabajadoras sexuales de Bogotá- 2015

Objetivo: Determinar un modelo predictivo para uso del condón y consumo de alcohol como conductas de riesgo relacionadas el contagio de VIH/Sida en mujeres trabajadoras sexuales de la ciudad de Bogotá en el año 2015. Métodos Estudio de tipo transversal con diseño observacional, se tomaron 255 mujeres trabajadoras sexuales de la ciudad de Bogotá; La información analizada fue tomada del estudio realizado en cinco ciudades de Colombia en el año 2015, las hipótesis planteadas se soportaron en la asociación entre las condiciones sociodemográficas, de conocimiento, practicas, hábitos, apoyo social y de ocupación propia de las mujeres trabajadoras sexuales que podían explicar y predecir la adopción de conductas riesgosas para VIH/sida como son el uso del condón y el consumo de alcohol en ejercicio de su ocupación. Resultados El promedio de edad de inicio en el trabajo sexual fue 22,1±7,1 años, tres cuartas partes son solteras y residen en estrato dos y tres; el 96,5% dijo usar el condón con el último cliente y el 27,8% de ellas consumió alcohol durante su último servicio. En la conducta de riesgo uso del condón, se encontraron asociados entre otras, la edad [OR=1,10(1,03-1,17)], vivir en estrato dos [OR=7,7(1,5-39,5)], el ingreso por trabajo sexual [OR=1,0(1,0-1,0)], la disponibilidad del condón para el servicio [OR=0,03(0,008-0,16)] y contar con otro método de planificación (ligadura de trompas) [OR=4,47(1,0-18,3)]. En la conducta de riesgo consumo de alcohol, se encontró asociado ente otros: estrato socioeconómico dos [OR=5,8(1,54-22,3)], nivel de escolaridad secundaria [OR=0,12(0,16-0,96)], vivir con otros familiares [OR=3,45(1,7-7,02)], ingreso por trabajo sexual [OR=1,0(1,0-1,0)] y el sitio donde se ofrece el servicio [OR=0,07(0,04-0,15)]. Después de ajustar, se encontró que las variables que mejor explican el uso del condón fueron edad [OR=1,1(1,02-1,17)] y disponibilidad del condón [OR=0,04(0,008-0,024)], el modelo tuvo poca sensibilidad 33,3% y buena capacidad predictiva (84,6%). Las variables que mejor explicaron el consumo de alcohol durante el servicio fueron edad [OR= 0,95(0,91-0,98)], Número de clientes por semana [OR=0,9(0,90-0,98)], sitio donde ofrece el servicio [OR=7,1(3,45-14,8)], y estrato socioeconómico [OR=1,8 (0,90-3,83)], resultando un modelo con buena sensibilidad (71,8%) y buena capacidad predictiva (86,4%). Conclusiones Aspectos como la edad, el estrato socioeconómico, escolaridad, estado civil, ingreso económico por trabajo sexual, edad de inicio en el trabajo sexual, número de clientes antiguos en la última semana, disponibilidad del condón para prestar el servicio y ligadura de trompas como método diferente de planificación, se asociaron estadísticamente con el uso del condón. Sin embargo al ajustar las variables solo la edad y la disponibilidad del condón se mantuvieron como variables explicativas. Cabe anotar, que aunque el modelo mostró buena capacidad predictiva (84,6%), la precisión en sus estimaciones fue baja debido a la poca frecuencia del no uso del condón con el ultimo cliente (3,5%), y la sensibilidad del modelo apenas fue del 33,3%. Por otro lado, factores como la edad, el estrato socioeconómico, nivel educativo, ingreso económico, sitio de oferta del servicio, composición familiar, número de hijos, número de clientes atendidos en la última semana y número de clientes antiguos mostraron asociación estadística con el consumo de alcohol. Sin embargo, al ajustar las variables solo edad, estrato socioeconómico, sitio donde se ofrece el servicio y número de clientes por semana mantuvieron asociación estadística; observándose además que el estrato socioeconómico (uno y dos) y sitio donde se ofrece el servicio (establecimiento), son factores de riesgo para el consumo de alcohol en ejercicio de la ocupación y la poca edad y un número reducido de clientes por semana se comportan como factores de protección para el consumo de alcohol. El modelo predictivo que se desarrolló para la conducta de riesgo de consumo de alcohol, con una sensibilidad del 71,8% y un poder predictivo del 86,4%. .

Censored Linear Regression Models For Irregularly Observed Longitudinal Data Using The Multivariate-t Distribution.

In acquired immunodeficiency syndrome (AIDS) studies it is quite common to observe viral load measurements collected irregularly over time. Moreover, these measurements can be subjected to some upper and/or lower detection limits depending on the quantification assays. A complication arises when these continuous repeated measures have a heavy-tailed behavior. For such data structures, we propose a robust structure for a censored linear model based on the multivariate Student's t-distribution. To compensate for the autocorrelation existing among irregularly observed measures, a damped exponential correlation structure is employed. An efficient expectation maximization type algorithm is developed for computing the maximum likelihood estimates, obtaining as a by-product the standard errors of the fixed effects and the log-likelihood function. The proposed algorithm uses closed-form expressions at the E-step that rely on formulas for the mean and variance of a truncated multivariate Student's t-distribution. The methodology is illustrated through an application to an Human Immunodeficiency Virus-AIDS (HIV-AIDS) study and several simulation studies.

Evolução de parâmetros antropométricos em portadores do vírus da Imunodeficiência Humana ou com Síndrome da Imunodeficiência Adquirida: um estudo prospectivo

OBJETIVO: Avaliar o estado nutricional e a evolução de parâmetros antropométricos para alterações morfológicas em pacientes vivendo com o vírus da Imunodeficiência Humana ou com Síndrome da Imunodeficiência Adquirida em uso de terapia antirretroviral de alta atividade. MÉTODOS: Trata-se de estudo de coorte prospectiva com duração de 12 meses, envolvendo indivíduos adultos, de ambos os sexos, em terapia antirretroviral recém introduzida. Os indicadores antropométricos estudados foram índice de massa corporal, circunferência de cintura, dobras cutâneas subescapular, biciptal e triciptal, avaliados com intervalos de três meses, totalizando 4 medidas do tempo. Variáveis foram descritas segundo mediana e percentis 25 e 75 e analisadas por ANOVA para medidas repetidas. RESULTADOS: A população estudada foi composta por 53 indivíduos, a maioria do sexo masculino (81%), entre 30 e 39 anos. Apenas a dobra cutânea subescapular apresentou significante variação no tempo (T1=13,7 vs T4=16,0; p<0,001), apontando para lipo-hipertrofia dorso-cervical. CONCLUSÃO: Os achados deste estudo, embora limitados, direcionam para a necessidade de vigilância de parâmetros antropométricos associados a alterações morfológicas, em especial, aqueles usados no diagnóstico de acúmulo de gordura abdominal e dorso-cervical.

Vaccination in Brazilian HIV-infected adults: A cross-sectional study

HIV-infected patients are at risk for vaccine-preventable infections. The Brazilian National Immunization Program provided recommendations for this population. However, the vaccine coverage reached by this program is unknown. This study aimed at evaluating the vaccine coverage of HIV-infected adults followed at Hospital das Clinicas, University of Sao Paulo School of Medicine. Data were collected on age, gender, mode of HIV transmission, Centers for Disease Classification 1993 classification (CDC/93), antiretrovirals, CD4 count, HIV viral load, and immunization charts, from April 2003 to August 2004. We interviewed 144 randomly selected patients, 74% male; mean age, 39.95 years; CDC classification: A, 40.6%; B, 19.6%; and C, 39.9%. Most of patients were undergoing highly active antiretroviral therapy (HAART; 86.8%). Mean CD4 count 442.6 cells/mm(3). Viral load less than 400 copies per milliliter in 59.4% of patients. Only 36.1% of patients were adequately immunized for diphtheria/tetanus, 54.9% for pneumococcus, 24.3% for flu, and 76.9% for hepatitis B. In relation to live attenuated vaccines, 5 patients received measles, mumps, and rubella vaccine and 7 patients yellow fever vaccine. Two patients were vaccinated against yellow fever despite CD4 less than 200 cell/mm(3). We verified poor vaccine coverage in HIV-infected patients. Vaccination campaigns and incorporation of vaccine rooms in sexually transmitted disease (STD)/AIDS clinics could improve this situation.