Terapêuticas que reduzem a transmissão vertical do HIV / Therapeutics that reduce vertical HIV transmission

O vírus da imunodeficiência humana (HIV) é um retrovírus com genoma ácido ribonucleico da família Retroviridae (retrovírus) e subfamília Lentivirinae, que necessita, para multiplicar-se, de uma enzima denominada transcriptase reversa, responsável pela transcrição do ácido ribonucleico viral para uma cópia de ácido desoxirribonucleico. A transmissão ocorre por via predo- minantemente sexual, mas também pelo contato com sangue contaminado, pela via transplacentária ou por aleitamento materno. A transmissão vertical é a principal via de infecção pelo HIV em crianças. É estimado que 15% a 30% da população infan til nascida de mães soropositivas para o vírus da imunodefici- ência humana adquirem o vírus com maior frequência durante o trabalho de parto, pós-parto ou por meio da amamentação. Tem-se utilizado para gestantes a terapia antirretroviral combi- nada, a qual reduziu 20 vezes nas taxas de transmissão vertical. O objetivo deste trabalho é discutir sobre as drogas que retar- dam a progressão da imunodeficiência, aumentando o tempo e a qualidade de vida do portador do vírus da imunodeficiência humana, além de especificar a terapia que obteve mais sucesso. O início de terapia antirretroviral combinada em uma fase precoce da gestação em pacientes infectadas tem o potencial de melhorar substancialmente a saúde materna e a sobrevida, além de tornar a transmissão vertical um evento raro.

The Human Immunodeficiency Virus (HIV) is a retrovirus with a ribonucleic acid (RNA) genome of the Retrovirus Family and subfamily Lentivirinae, which needs an enzyme called reverse transcriptase to be multiplied, which is responsible for trans- cribing viral ribonucleic acid to a deoxyribonucleic acid (DNA) strand. Transmission occurs predominantly sexually, but also through contact with blood, transplacental, or through breastfee- ding. Vertical transmission is the main route of HIV infection in children. It is estimated that 15 to 30% of the child population born to HIV-positive mothers acquire the virus most often du- ring labor, postpartum, or through breastfeeding. Highly Active Antiretroviral Therapy has been used for pregnant women, with 20-fold reduction of vertical transmission rates. The aim of this paper is to discuss about the drugs that slow the progression of immunodeficiency, increasing the time and quality of life of pa- tients with Human Immunodeficiency Virus, and specifying the most successful therapy. Initiation of Highly Active Antiretro- viral Therapy at an early stage of pregnancy in infected patients has the potential to improve maternal health and survival subs- tantially, and makes vertical transmission a rare event.

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Hepatitis B viremia in HIV-coinfected individuals under antiretroviral therapy

ABSTRACT Background: Antiretroviral therapy (ART) has decreased AIDS incidence and mortality, rendering comorbidities, such as hepatitis B more relevant for people living with human immunodeficiency virus (HIV). Since antiretroviral drugs may also inhibit hepatitis B virus (HBV) replication, analyzing the impact of ART on management of hepatitis B in this population is important. Objective: To assess HBV viremia among HIV/HBV coinfected individuals on ART and its associated factors. Method: For this cross-sectional study, HIV/HBV-coinfected individuals, aged over 18 years, who were on ART for over six months and receiving care at an outpatient clinic in São Paulo were recruited. Sociodemographic characteristics, information about viral exposure, clinical and laboratory data, including evaluation of liver fibrosis were obtained. Plasma HBV DNA was measured by polymerase chain reaction. Viral genome sequencing was conducted for genotyping and identification of drug resistance-conferring mutations if viral load exceeded 900 IU/mL. Results: Out of 2,946 patients who attended the clinic in 2015, 83 were eligible and 56 evaluated. Plasma HBV DNA was detected in 16 (28.6%) (95% CI: 18.0-41.3%), all on lamivudine and tenofovir treatment. HBV DNA detection was associated with lower education (p = 0.015), higher international normalized ratios (p = 0.045), history of an AIDS-defining illness [OR: 3.43 (95% CI: 1.10-11.50)], and HBeAg detection [OR: 6.60 (95% CI: 1.84-23.6)]. In contrast, a last CD4+ count above 500 cells/mm3 in the year prior to inclusion [OR: 0.18 (95% CI: 0.04-0.71)] and detection of anti-HBe [OR: 0.21 (95% CI: 0.04-0.99)] were negatively associated. Patients with HBV DNA above 900 IU/mL were infected with subgenotypes A1 (n = 3) and D2 (n = 1), and exhibited viral mutations associated with total resistance to lamivudine and partial resistance to entecavir. Conclusions: Despite being on ART, a significant proportion of HIV/HBV-coinfected individuals present HBV viremia. Characterization of factors that are associated with this finding may help professionals provide better management to these patients.

Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV

BACKGROUND Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.

Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals / Segurança do monitoramento da resposta à terapia antirretroviral em pacientes com infecção pelo HIV-1 através da contagem de linfócitos T CD4+ a intervalos mais longos / Seguridad en la monitorización de la respuesta a la terapia antirretroviral ante el VIH-1, usando el recuento celular CD4+ T en intervalos a largo plazo

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

Resumo: O último consenso brasileiro recomenda reduzir a rotina de contagem de linfócitos T CD4+ para monitorar os pacientes com HIV-1 sob terapia antirretroviral combinada (TARV). O estudo teve como objetivo avaliar a segurança do monitoramento à TARV na infecção pelo HIV-1, realizando a carga viral a intervalos mais curtos e a contagem de linfócitos T CD4+ a intervalos mais longos. Foram avaliadas a contagem de linfócitos T CD4+ e a carga viral do HIV-1 em 1.906 pacientes com HIV-1 em uso de TARV durante um seguimento de três anos. Os pacientes foram estratificados em: resposta sustentada, não sustentada e não respondedores. As proporções de pacientes com linfócitos T CD4+ > 350células/µL na linha de base do estudo entre de resposta sustentada, não sustentada e não respondedores à TARV e que permaneceram com valores acima desse limiar ao longo do seguimento foram 94,1%, 81,8% e 71,9%, respectivamente. Os pacientes com resposta virológica sustentada e que tinham contagem de T CD4+ > 350células/µL mostraram maior probabilidade de manter a contagem acima desse limiar durante o seguimento, quando comparados àqueles com T CD4+ ≤ 350células/µL (OR = 39,9; 95%CI: 26,5-60,2; p < 0,001). O estudo mostrou que pacientes HIV-1+ com resposta virológica sustentada e contagem de linfócitos T CD4+ > 350células/µL tinham maior probabilidade de manter a contagem de células T CD4+ acima desse limiar durante o seguimento de três anos subsequentes. O resultado corrobora que a contagem de linfócitos T CD4+ com intervalos mais longos não compromete a segurança do monitoramento da resposta à TARV quando a avaliação da carga viral é feita de rotina em pacientes HIV-1+ com resposta virológica sustentada.

Resumen: Las últimas directrices brasileñas recomendaron la reducción de la rutina en el recuento celular CD4+ T para pacientes con el virus de inmunodeficiencia humano tipo 1 (VIH-1), con terapia de combinación antirretroviral (cART por sus siglas en inglês). El objetivo de este estudio fue evaluar la seguridad de la monitorización de la respuesta a la cART en una infección por VIH-1, usando rutinas de carga viral en intervalos más cortos y recuento celular CD4+ T en intervalos más largos. Se evaluaron el recuento celular CD4+ T y la carga viral VIH-1 en 1.906 pacientes infectados con VIH-1 y con cART durante un seguimiento que duró tres años. Los pacientes fueron estratificados como constantes, inconstantes y sin respuesta. La proporción de pacientes que mostraron CD4+ T > 350células/µL en el estudio entran dentro del grupo de los constantes, inconstantes y sin respuesta al cART, y quienes permanecieron con valores por encima de este umbral durante los seguimientos fueron 94,1%, 81,8% y 71,9%, respectivamente. Los pacientes infectados por VIH-1 que cuentan con la respuesta virológica constante y tienen un recuento inicial CD4+ T > 350células/µL mostraron una oportunidad más alta de mantener el recuento de estas células por encima del umbral durante los seguimientos, respecto a quienes presentaban CD4+ T células ≤ 350células/µL (OR = 39,9; IC95%: 26,5-60,2; p < 0,001). Este estudio expuso que los pacientes infectados por VIH-1, que habían tenido una respuesta virológica constante e inicial CD4+ T > 350células/µL, eran más propensos a mantener el recuento de células CD4+ T por encima de este umbral durante los tres años posteriores de seguimiento. Este resultado destaca que la evaluación del cómputo de células CD4+ T en intervalos más largos no obstaculiza la seguridad al realizar una monitorización en la respuesta a cART, cuando la evaluación de la carga viral rutinaria se realiza en pacientes infectados por VIH-1 con una respuesta virológica constante.

Effectiveness of antiretroviral therapy in the single-tablet regimen era / Efetividade da terapia antirretroviral na era de medicamentos em dose fixa combinada

ABSTRACT OBJECTIVE To evaluate the effectiveness of antiretroviral therapy and the associated factors according to the type of regimen used: Single Tablet Regimen or Multiple Tablet Regimen. METHODS Prospective cohort of 440 patients (male, 74.3%, median age, 36 years old) who initiated antiretroviral therapy between Jan/14 and Dec/15 at a referral service in Belo Horizonte. Efficacy was defined as viral suppression (viral load, VL < 50 copies/ml) and evaluated after six and twelve months of treatment. Sociodemographic, clinical and behavioral data were collected from clinical charts and from Information Systems. Multivariate analysis of overall effectiveness was performed by logistic regression. RESULTS Most patients initiated Multiple Tablet Regimen antiretroviral therapy (n = 255, 58%). At six months, overall viral suppression was 74.6%, being higher among patients who used Single Tablet Regimen (80.6%, p = 0.04). At twelve months, 83.2% of patients reached viral suppression, with no difference between groups (p = 0.93). Factors independently associated with viral suppression at six and twelve months varied, being negatively associated with effectiveness: VL ≥ 100,000 copies/ml, symptoms of AIDS, longer interval time between diagnosis and initiation of antiretroviral therapy, antiretroviral switching, smoking or current illicit drugs usage (p < 0.05). Factors positively associated with viral suppression included adherence to antiretroviral therapy and category of risk/exposure of men who have sex with men (p < 0.05). Reaching viral suppression at six months was the main predictor of effectiveness at one year (OR = 8.96 and p < 0.01). CONCLUSIONS Viral suppression was high and better results were achieved for patients who used Single Tablet Regimen regimens at six months. Clinical, behavioral, and antiretroviral therapy -related factors influence viral suppression and highlight the need for interventions to increase early diagnosis and initiation of antiretroviral therapy, patient's adherence, and to reduce illicit drugs and cigarette smoking in this population.

RESUMO OBJETIVO Avaliar a efetividade da terapia antirretroviral e fatores associados segundo o tipo de esquema utilizado: medicamento em dose fixa combinada ou múltiplos medicamentos e doses. MÉTODOS Coorte prospectiva não concorrente de 440 pacientes que iniciaram terapia antirretroviral entre janeiro de 2014 e dezembro de 2015 em Belo Horizonte, MG. A efetividade foi definida como supressão viral (carga viral [CV] < 50 cópias/ml) e avaliada após seis e 12 meses de tratamento. Dados sociodemográficos, clínicos e comportamentais foram coletados de prontuário clínico e de sistemas de informação. A análise múltipla da efetividade global foi realizada por regressão logística. RESULTADOS A maioria dos pacientes iniciou terapia antirretroviral com múltiplos medicamentos e doses (58%). Aos seis meses, a supressão viral global foi 74,6%, maior entre pacientes que utilizaram dose fixa combinada (80,6%; p = 0,04). Aos 12 meses, 83,2% dos pacientes atingiram supressão viral, sem diferença entre os grupos (p = 0,93). Fatores independentemente associados à supressão viral em seis e 12 meses variaram, e foram negativamente associados à efetividade: CV ≥ 100.000 cópias/ml, sintomas definidores de aids, maior intervalo de tempo entre diagnóstico e início da terapia antirretroviral, troca de antirretroviral e consumo de tabaco ou drogas ilícitas (p < 0,05). Fatores positivamente associados à supressão viral incluíram adesão à terapia antirretroviral e categoria de risco/exposição de homens que fazem sexo com homens (p < 0,05). Atingir supressão viral aos seis meses foi o principal preditor de efetividade em um ano (OR = 8,96; p < 0,01). CONCLUSÕES A supressão viral foi elevada e superior para pacientes que utilizaram esquemas de dose fixa combinada aos seis meses. Fatores clínicos, comportamentais e relacionados à terapia antirretroviral influenciaram a supressão viral e evidenciam a necessidade de intervenções para aumentar o diagnóstico, o início precoce e a adesão dos pacientes à terapia antirretroviral, bem como reduzir o uso de drogas ilícitas e tabaco nesta população.

Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

ABSTRACT Objective: To evaluate the virological outcomes in children and adolescents infected with HIV-1 in Salvador, Bahia according to genotyping results. Methods: We retrospectively evaluated the rates of virological suppression of children and adolescents submitted to HIV-1 genotyping test from January/2008 to December/2012. The participants were followed in the two referral centers for pediatric AIDS care, in Salvador, Brazil. Resistance mutations, drug sensitivity profiles, and viral subtypes were analyzed using the Stanford HIV-1 Drug Resistance Database. Adherence was estimated by drugs withdrawal at pharmacies of the two sites. Results: 101 subjects were included: 35 (34.6%) were drug-naïve, and the remaining 66 were failing ART. In drug-naïve group, 3 (8.6%), presented with NNRTIs resistance mutations, along with polymorphic mutations to PIs in most (82.8%) of them. Among the failing therapy group, we detected a high frequency (89.4%) of resistance mutations to PIs, NRTI (84.8%), and NNRTI (59.1%). Virological suppression after introduction/modification of genotyping-guided ART was achieved only for patients (53.1%) with drug withdrawal over 95%. Main detected HIV-1 subtypes were B (67.3%), F (7.9), C (1.9%), and recombinant forms (22.9%). Conclusions: Despite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.

Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection

Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.

Carga viral comunitária do HIV no Brasil, 2007 - 2011: potencial impacto da terapia antirretroviral (HAART) na redução de novas infecções / Community viral load of HIV in Brazil, 2007 - 2011: potential impact of highly active antiretroviral therapy (HAART) in reducing new infections

RESUMO: Objetivo: Estimar o volume de vírus circulante de HIV na população brasileira e avaliar o potencial impacto da terapia antirretroviral (HAART) na redução de novas infecções, com o propósito de construir evidências e informações para subsidiar a implementação de políticas de saúde. Métodos : Ferramentas de análise espacial foram utilizadas para descrever os padrões existentes na densidade da carga viral utilizando o método Kernel quártico. As informações da carga viral e tratamento são oriundas da base conjunta do Sistema de Controle de Exames Laboratoriais (Siscel), com informações do histórico da carga viral do indivíduo e do Sistema de Controle Logístico de Medicamentos (Siclom), que controla a dispensa dos medicamentos para a terapia antirretroviral. Resultados: Observou-se que a carga viral comunitária (CVC) apresentou redução progressiva no período de 2007 a 2011, acompanhada de uma redução da carga viral média (CVCM) superior a 32% (22.900 cópias/mL em 2007 versus 15.418 cópias/mL em 2011). Nesse período, houve redução da CVCM em todas as grandes regiões do Brasil, embora o Norte e Nordeste tenham apresentado, respectivamente, CVCM 1,7 e 1,5 vezes a registrada no Sudeste. Em uma comparação entre os indivíduos que faziam ou não uso da HAART, observou-se aumento persistente da carga viral naqueles que não faziam uso da terapia de até 3,9 vezes em 2011. Conclusão: A abordagem apresentada neste estudo aponta a existência de aglomerados no espaço com altas concentrações. O uso do Kernel na identificação de aglomerados no espaço mostrou-se um bom instrumento para análise exploratória, possibilitando a visualização do risco em determinadas áreas geográficas sem as usuais divisões político-administrativas.

ABSTRACT: Objectives: To estimate the human immunodeficiency virus (HIV) viral load in the Brazilian population and to assess the potential impact of highly active antiretroviral therapy (HAART) in reducing new infections to build evidences and to gather information to support health policies. Methods: Spatial analysis and modeling tools were used to describe the existing patterns of the viral load density, using the Kernel method. Data on viral load and treatment were retrieved from the databases Laboratory Tests Control System (SISCEL), which contains information on the individual's history of viral load, and Medication Logistics Control System (SICLOM), which controls the dispensing of drugs used for antiretroviral therapy. Results: It was observed that the community viral load (CVL) decreased progressively from 2007 to 2011, accompanied by a decrease of more than 32% in the mean CVL (CVLM) - 22,900 copies/mL in 2007 versus 15,418 copies/mL in 2011. During this period, there was a reduction of CVLM in all regions of Brazil, although North and Northeast showed, respectively, CVLM 1.7 and 1.5 times higher than that in the Southeast region. A comparison between the individuals who underwent and who did not undergo HAART showed an increase of up to 3.9 times in 2011 in the viral load among those who did not undergo the therapy. Conclusion: The approach presented in this study indicates the existence of clusters with high concentrations. The use of Kernel in the identification of clusters proved to be a good tool for exploratory analysis, enabling the risk identification in certain geographic areas without the usual political and administrative divisions.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p = 0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio = 4.1, 95% confidence interval: 1.8-9.1; p < 0.001), but not at enrollment or the 6-month visit (p > 0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p < 0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p ≤ 0.005), but not at the 6-month visit (p = 0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

Long-Term Outcomes and Dynamics of Mutants Associated with Lamivudine-Adefovir Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

BACKGROUND/AIMS: To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B. METHODS: Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations. RESULTS: The median duration of LAM-ADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response. CONCLUSIONS: The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.

Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study / Supressão viral e adesão entre crianças e adolescentes vivendo com HIV na terapia antirretroviral: resultados de um estudo multicêntrico

OBJECTIVE: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV) patients followed in pediatric centers in Brazil. METHODS: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF), anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL) < 50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. RESULTS: 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL < 50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL < 50 copies/mL (p ≤ 0.01). Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR = 0.49; 95% CI: 0.27-0.89) and median interval between pharmacy visits < 33 days (OR = 0.97; 95% CI: 0.95-0.98) were independently associated with VL < 50 copies/mL; whereas lower caregiver scores for anxiety (OR = 2.57; 95% CI: 1.27-5.19) and children's HIV diagnosis for screening due to maternal infection (OR = 2.25; 95% CI: 1.12-4.50) were found to be independently associated with 100% adherence. CONCLUSIONS: Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence. .

OBJETIVO: Avaliar a adesão ao tratamento antirretroviral entre portadores de HIV acompanhados em centros pediátricos. MÉTODOS: Trata-se de estudo transversal multicêntrico. Os prontuários ambulatoriais foram revistos e aplicadas escala de adesão, avaliação de qualidade de vida (WHOQOL-BREF), ansiedade, depressão e uso indevido de álcool/substâncias entre cuidadores. Os desfechos incluíram autorrelato 100% de adesão nos últimos três dias e carga viral do HIV (CV) < 50 cópias/mL. RESULTADOS: 260 indivíduos foram incluídos, 79% crianças e 21% adolescentes; 93% das crianças e 77% dos adolescentes relataram 100% de adesão; 57% das crianças e 49% dos adolescentes tinham CV < 50 cópias /mL. Na análise univariada, diagnóstico do HIV por triagem devido à infecção materna, cuidador com pontuação menor para ansiedade e maior nos domínios físico e psicológico do WHOQOL-BREF se mostraram independentemente associados a 100% de adesão. Intervalos mais curtos entre visitas de farmácia foram associados com CV < 50 cópias /mL (p ≤ 0,01). Regressão multivariada mostrou que os cuidadores sem abuso de álcool/outras drogas (OR = 0,49; IC95% 0,27-0,89) e o intervalo médio entre visitas de farmácia < 33 dias (OR = 0,97; IC95% 0,95-0,98) foram associados com CV < 50 cópias/mL; cuidador com menores escores para ansiedade (OR = 2,57; IC95% 1,27-5,19) e diagnóstico de crianças por triagem devido à infecção materna (OR = 2,25; IC95% 1,12-4,50) foram associados com 100% de adesão. CONCLUSÕES: Programas de HIV pediátrico devem avaliar qualidade de vida e sintomas de ansiedade e depressão dos cuidadores. Registros de farmácia são essenciais na identificação de adesão ...

Linfocitos TCD4+ y carga viral en pacientes con debut de sida que reciben tratamiento antirretroviral / CD4 + T lymphocytes and viral load in patients with AIDS debut receiving antiretroviral therapy

INTRODUCCIÓN: el debut de sida es una forma de presentación de la enfermedad causada por VIH que se caracteriza por alteración del estado general del paciente, síndrome de desgaste, aparición de graves infecciones oportunistas, neoplasias y alteraciones neurológicas. MÉTODOS: se estudió el comportamiento de los niveles de linfocitos T CD4+ y de carga viral en pacientes con debut de sida y terapia antirretroviral, al inicio y un año después del tratamiento. Se estudiaron 55 pacientes los cuales tuvieron al inicio del tratamiento conteos de linfocitos TCD4+ inferiores a 200cel/µL y carga viral elevada. RESULTADOS: después de un año de terapia, los valores de linfocitos T CD4+ aumentaron por encima de 200 cel/µL y la carga viral disminuyó a niveles no detectables en los pacientes estudiados. CONCLUSIONES: los resultados de esta investigación confirman los beneficios del tratamiento antirretroviral particularmente para los pacientes con debut de sida.

INTRODUCTION: the AIDS premiere is a form of presentation of the illness caused by HIV that is characterized by alteration of the patient's general state, waste syndrome, appearance of serious opportunists infections, neoplasia and neurological alterations. METHODS: the behavior of the CD4+ T lymphocytes levels were studied and of viral load in patient with AIDS premiere and antiretroviral therapy, to the beginning and one year after the treatment. 55 patients those were studied which had to the beginning of the treatment CD4+ T lymphocytes counts less to 200cel/µL and high viral load. RESULTS: after a year of therapy, the values of CD4+ T cells recovered and the viral load diminished at non detecting levels in the evaluated patients. CONCLUSIONS: the results of this study confirm the benefits of antiretroviral therapy, particularly for patient with AIDS premiere.

Impacto de la inmunodepresión basal y su grado de recuperación al año de terapia antirretroviral en sobrevida, complicaciones oportunistas y reacción de recuperación inmune / Impact of baseline CD4 count, immune recoveny and viral suppression at 7 year of first highly active antiretroviral therapy on survival, AIDS defining events and immune recovery reactions

Background: Baseline (BL) CD4 cell count is a major factor in outcome of highly active antiretroviral therapy (HAART); treatment induced immune recovery and viral response can modulate this outcome. Aim: To evaluate the association between baseline CD4 cell count and outcome during the first HAART régimen. Material and methods: Prospective study in 2,050 patients on first HAART with a follow up (f/u) ofat least 1 year. All had BL CD4 and viral load (VL) counts which were repeated at least twice a year. Patients were grouped according to BL CD4 (cells/mm³) in <100 (Gl), 100-199 (G2) and ≥ (G3). Groups were further divided according to immune and vírologícal response at 1 year in CD4 > or < 200 and VL detectable or undetectable (<80 copies/mL). Outcome measures were death, ALUS defining events (ADE) and, as a surrogate marker of immune recovery reaction, herpes zoster (HZ). Resulte: During the first year of follow up, 113 patients (10.8 percent) diedin Gl (n =1,044), 17 (2.5 percent) in G2 (n =675) (Gl-2 p <0.05) and 9 (2.7 percent) in G3 (n =331) (G2-3 p NS). One hundred twenty five of919 (13.6 percent) patients alive at 1 year had ADE in Gl, 55/643 (8.5 percent) in G2 (p <0.05) and 20/320 (5.2 percent) in G3 (G2-3 p NS). ADEs with follow up CD4 >vs< 200 were: 25/274 (9.1 percent) vs 100/643 (15 7 percent) in Gl (p <0.005); 28/404 (6.9 percent) vs 27/235 (11.2 percent) in G2 (p NS) and 18/281 (6.4 percent) vs 2/41 (4.8 percent) in G3 respectively (p NS). Detectable VL was an additional risk for ADE only in Gl without CD4 recovery. HZ was seen in 6.6 percent of Gl vs 4 percent in G2 (p <0.05) and 4.3 percent in G3. HZ rate was higher in all groups reaching a follow up CD4 >200 than those who did not, with a statistically significant difference at p <0.05 only in Gl (9.5 percent vs 5.3 percent). Conclusions: The occurrence of death and ADE during the first year of HAART was significantly higher in patients with aBL CD4...