Evaluation of HIV-1 resistance to antiretroviral drugs among 150 patients after six months of therapeutic interruption

Most of the antiretroviral (ARV) studies in Brazil have been reported in treatment-experienced and naive patients rather than in the setting of treatment interruption (TI). In this study, we analysed reasons given for TI and resistance mutations occurring in 150 HIV-1-infected patients who underwent TI. Of the patients analysed, 110 (73.3%) experienced TI following medical advice, while the remaining patients stopped antiretroviral therapy (ART) of their own accord. The main justifications for TI were: ARV-related toxicities (38.7%), good laboratory parameters (30%) and poor adherence (20%). DNA sequencing of the partial pol gene was successful in 137 (91.3%) patients, of whom 38 (27.7%) presented mutations conferring ARV resistance. A higher viral load prior to TI correlated with drug resistance (P < 0.05). Our results demonstrate that there are diverse rationales for TI and that detection of resistant strains during TI most likely indicates a fitter virus than the wild type. High viral loads coupled with unprotected sex in this group could increase the likelihood of transmission of drug-resistant virus. Thus, treating physicians should be alerted to this problem when the use of ARVs is interrupted.

Evaluation of inadequate anti-retroviral treatment in patients with HIV/AIDS

Introduction: Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. Methods: A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. Results: The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 +/- 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/lamivudine was used, the patients were less compliant (chi(2) = 4.468, 1 degree of freedom, p = 0.035). Conclusions: The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.

An in-depth analysis of the HIV-1/AIDS dynamics by comprehensive mathematical modeling

This work presents major results from a novel dynamic model intended to deterministically represent the complex relation between HIV-1 and the human immune system. The novel structure of the model extends previous work by representing different host anatomic compartments under a more in-depth cellular and molecular immunological phenomenology. Recently identified mechanisms related to HIV-1 infection as well as other well known relevant mechanisms typically ignored in mathematical models of HIV-1 pathogenesis and immunology, such as cell-cell transmission, are also addressed. (C) 2011 Elsevier Ltd. All rights reserved.

Candida albicans Isolation from Buccal Mucosa of Patients with HIV Wearing Removable Dental Prostheses

Purpose: The aim of this study was to evaluate the influence of complete or partial removable dental prostheses (RDPs) on the frequency of Candida albicans isolated from the mouth and the presence of oral candidiasis in human immunodeficiency virus positive (HIV+) patients correlated with CD4 levels. Materials and Methods: One hundred ninety-three HIV+ patients were evaluated; 68 had RDPs and 125 did not. CD4 cell count was obtained after blood sampling and performed on the day of clinical examination. The material was collected from the buccal mucosa for isolation of yeasts with a sterile swab and seeded onto Sabouraud dextrose agar with chloramphenicol. C albicans strains were identified by testing germ tubes and chlamydospore formation and biochemical (zymogram, auxanogram) characteristics. The results were subjected to the Fischer exact test and chi-square tests. Results: C albicans were isolated from 45(66.17%) patients who had RDPs and 48 (38.4%) who did not (P = .0003). The presence of oral candidiasis was observed in 14 patients (7.25%), and 10 of the 14 (71.43%) were RDP users. The absence of candidiasis occurred in 121 (67.59%) nonusers and 58 (32.40%) users of RDPs (P = .0065). The mean CD4 cell count was lower in patients with oral candidiasis regardless of the use of RDPs. Conclusion: The use of RDPs was an important factor in the isolation of C albicans among HIV+ patients, and CD4 level seems to play a role in the presence of oral candidiasis. Int J Prosthodont 2012;25:127-131.

Manifestações orais em crianças HIV, em Moçambique

O objetivo foi comparar conhecimento de homens idosos ao de adultos jovens sobre Aids, considerando escolaridade. Estudo epidemiológico, descritivo e de corte transversal, em que foram analisadas informações de 30 idosos e 62 adultos jovens sobre conceito, transmissão, prevenção, diagnóstico e tratamento de Aids, investigadas por entrevista estruturada baseada em questionário validado padronizado. Para análise de contingência e de variância, empregaram-se distribuições de frequências e testes de Qui quadrado ou exato de Fisher e teste t de Student ou Mann-Whitney em nível de significância de 0,05. Foram empregados o teste de Mantel-Haenszel, em nível de significância de 0,05, e os Odds Ratio com intervalos de confiança a 95%, para influência da escolaridade. Constataram-se percepção individual de boa saúde maior em jovens (61,3% contra 43,3% dos idosos) e atividade sexual maior em idosos (80% contra 62,9% dos jovens). Apesar disso foi menos frequente idosos afirmarem conhecimento satisfatório sobre Aids (26,7% contra 80,6% dos jovens); história de teste de HIV (13,3% contra 24,2% dos jovens) e ter recebido orientação sobre Aids (36,7% dos idosos e 98,4% dos jovens). Os idosos tinham informação insuficiente sobre HIV/Aids comparados a adultos jovens, reforçando a necessidade de maior atenção à população idosa.

Hypermetabolism and altered substrate oxidation in HIV-infected patients with lipodystrophy

Objective: Human immunodeficiency virus type 1 (HIV)-associated lipodystrophy syndrome compromises body composition and produces metabolic alterations, such as dyslipidemia and insulin resistance. This study aims to determine whether energy expenditure and substrate oxidation are altered due to human HIV-associated lipodystrophy syndrome. Methods: We compared energy expenditure and substrate oxidation in 10 HIV-infected men with lipodystrophy syndrome (HIV+LIPO+), 22 HIV-infected men without lipodystrophy syndrome (HIV+LIPO-), and 12 healthy controls. Energy expenditure and substrate oxidation were assessed by indirect calorimetry, and body composition was assessed by dual-energy X-ray absorptiometry. The substrate oxidation assessments were performed during fasting and 30 min after eucaloric breakfast consumption (300 kcal). Results: The resting energy expenditure adjusted for lean body mass was significantly higher in the HIV+LIPO+ group than in the healthy controls (P = 0.02). HIV-infected patients had increased carbohydrate oxidation and lower lipid oxidation when compared to the control group (P < 0.05) during fasting conditions. After the consumption of a eucaloric breakfast, there was a significant increase in carbohydrate oxidation only in the HIV+LIPO- and control groups (P < 0.05), but there was no increase in the HIV+LIPO+ group. Conclusion: Hypermetabolism and alteration in substrate oxidation were observed in the HIV+LIPO+ group. (C)2012 Elsevier Inc. All rights reserved.

Can an immune-regulatory vaccine prevent HIV infection?

Developing vaccines to prevent the establishment of HIV infection has been fraught with difficulties. It might therefore be important to consider other new strategies. Since several studies suggest that anti-inflammatory stimuli can protect from HIV infection and because HIV replicates preferably in activated T cells, we suggest here that the reduction of immune activation through a HIV-specific regulatory T-cell vaccine might thwart early viral replication. Thus, because immune activation is a good predictor of disease progression and the immune activation set point has been shown to be an early event during HIV infection, vaccinating to achieve control of early virus-specific immune activation might be advantageous.

HPV type infection in different anogenital sites among HIV-positive Brazilian women

Abstract Objectives To evaluate the prevalence of human papillomavirus (HPV) types, and risk factors for HPV positivity across cervix, vagina and anus, we conducted a study among 138 women with human immunodeficiency virus (HIV). Goal Compare the prevalence of different HPV types and the risk factors for HPV positivity in three sites. Results The most frequently detected HPV types in all sites were, in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and vagina was good (kappa 0.60 – 0.80) for HPV16 and 53 and excellent (Kappa > 0.80) for HPV18 and 61. HPV positivity was inversely associated with age for all combinations including the anal site. Conclusion In HIV positive women, HPV18 is the most spread HPV type found in combinations of anal and genital sites. The relationship of anal to genital infection has implications for the development of anal malignancies. Thus, the efficacy of the current HPV vaccine may be considered not only for the cervix, but also for prevention of HPV18 anal infection among immunossuppressed individuals.

HTLV-1/2 seroprevalence and coinfection rate in Brazilian first-time blood donors: an 11-year follow-up

The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeirão Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.

Terapia antirretroviral altamente eficaz para infecção pelo vírus da imunodeficiência humana aumenta a rigidez aórtica

FUNDAMENTO: Sabe-se que a terapia antirretroviral altamente potente para Aids reconhecida aumenta o risco cardiovascular, mas os efeitos dos agentes antirretrovirais de acordo com o gênero ainda são desconhecidos. OBJETIVO: O presente estudo avaliou o impacto do tratamento para o vírus da imunodeficiência humana (HIV) na rigidez aórtica de acordo com o gênero. MÉTODOS: Foram recrutados 28 pacientes com Aids submetidos à terapia antirretroviral altamente potente (HAART), 28 pacientes infectados pelo HIV virgens de tratamento, 44 pacientes com diabetes tipo 2, e 30 controles. A rigidez aórtica foi determinada pela medição da Velocidade da Onda de Pulso (VOP), utilizando um equipamento automático validado e não invasivo. RESULTADOS: Os resultados médios brutos da VOP (e intervalo de confiança de 95%) para participantes nos grupos terapia antirretroviral potente, HIV virgem de tratamento, diabéticos, e controles foram 9,77 m/s (9,17-10,36), 9,00 m/s (8,37-9,63), 9,90 m/s (9,32-10,49) e 9,28 m/s (8,61-9,95), respectivamente, para os homens (p de tendência = 0,14) e 9,61 m/s (8,56-10,66), 8,45 m/s (7,51-9,39), 9,83 (9,21-10,44) e 7,79 m/s (6,99-8,58), respectivamente, para as mulheres (p valor de tendência < 0,001). Análises post-hoc revelaram uma diferença significativa entre os valores médios de VOP no grupo com HAART e controles em mulheres (p < 0,01). Ajustes para as demais covariáveis potenciais, incluindo pressão arterial sistólica e diabetes, não alteraram esses resultados. Os achados indicam que o impacto do tratamento com HAART na rigidez aórtica foi amplificado nas mulheres com hipertensão, dislipidemia e síndrome metabólica. CONCLUSÃO: Agentes antirretrovirais potentes utilizados no tratamento da infecção pelo HIV aumentam a rigidez da aorta, especialmente em mulheres com maior risco cardiovascular.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Avaliação do acesso ao tratamento de tuberculose por coinfectados ou não pelo vírus da imunodeficiência humana

Este estudo objetivou avaliar o acesso ao tratamento das pessoas com tuberculose tanto coinfectadas ou não pelo Vírus da Imunodeficiência Humana (HIV). Trata-se de estudo transversal - com utilização do instrumento Primary Care Assessment Tool aplicado a 95 pessoas - que abordou questões sobre o acesso ao tratamento em município do interior paulista. Para avaliação do acesso ao tratamento, utilizou-se o teste t de Student. Os escores médios das variáveis foram analisados individualmente e comparados entre os dois grupos (pessoas com TB e coinfectadas com HIV e pessoas com TB não coinfectadas pelo HIV). Os escores médios mostraram que as coinfectadas pelo HIV apresentaram maiores dificuldades na obtenção do acesso do que as não coinfectadas. Os profissionais visitavam mais vezes as coinfectadas quando comparadas às não coinfectadas; as coinfectadas quase nunca realizavam o tratamento da doença em posto de saúde perto de sua residência. Há, portanto, necessidade de maior integração e comunicação entre os Programas de Tuberculose e DST/aids.

Coinfecção de Tb/HIV em um distrito administrativo do município de São Paulo

OBJETIVO: caracterizar o perfil sóciodemográfico e epidemiológico de pessoas com co-infecção Tb/HIV, residentes no distrito administrativo Capão Redondo do Município de São Paulo no período de 2000 a 2009. MÉTODOS: Trata-se de um estudo retrospectivo. RESULTADOS: De um total de 1.612 casos de tuberculose, 162 casos foram positivos para o HIV. Houve predomínio da faixa etária de 30 a 39 anos (39,5%), sexo masculino (61,1%) e a forma pulmonar (68,5%). Apenas 47,5% dos casos evoluíram para a cura, 13% abandonaram o tratamento e 32,2% foram a óbito. RESULTADOS: Ressalta-se a necessidade do conhecimento da situação da co-infecção Tb/HIV no sentido de oferecer uma assistência adequada a esta clientela, considerando que ambas as enfermidades não podem ser discutidas isoladamente. CONCLUSÃO: Conclui-se que os casos de associação Tb/HIV contribuem para a não adesão ao tratamento e aumento da taxa de mortalidade.

A comparative analysis of outpatient costs in HIV treatment programs

OBJECTIVE: To analyze the costs of human immunodeficiency virus (HIV) outpatient treatment for individuals with different CD4 cell counts in the Brazilian public health system, and to compare to costs in other national health systems. METHODS: A retrospective survey was conducted in five public outpatient clinics of the Brazilian national HIV program in the city of São Paulo. Data on healthcare services provided for a period of one year of HIV outpatient treatment were gathered from randomly selected medical records. Prices of inputs used were obtained through market research and public sector databases. Information on costs of HIV outpatient treatment in other national health systems were gathered from the literature. Annual costs of HIV outpatient treatment from each country were converted into 2010 U.S. dollars. RESULTS: Annual cost of HIV outpatient treatment for the Brazilian national public program was US$ 2,572.92 in 2006 in São Paulo, ranging from US$ 1,726.19 for patients with CD4 cell count > 500 to US$ 3,693.28 for patients with 51 < CD4 cell count < 200. Antiretrovirals (ARVs) represented approximately 62.0% of annual HIV outpatient costs. Comparing among different health systems during the same period, HIV outpatient treatment presented higher costs in countries where HIV treatment is provided by the private sector. CONCLUSION: The main cost drivers of HIV outpatient treatment in different health systems were: ARVs, other medications, health professional services, and diagnostic exams. Nevertheless, the magnitude of cost drivers varied among HIV outpatient treatment programs due to health system efficiency. The data presented may be a valuable tool for public policy evaluation of HIV treatment programs worldwide.

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.