Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection

The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real-time PCR; intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. Mean nucleotide diversity (π) and normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Compared to PREART, M12ART saw an immunological recovery with a gain of ∼200 CD4+ T cells (P = 0.008) and a normalization of the CD4/CD8 ratio [1.0 (IQR: 0.88–1.18), P = 0.016], as well as a significant decrease in HIV-1 RNA (∼4 log, P = 0.004) and DNA (∼1 log, P = 0.002) levels. The median time to achieve viral suppression was 3 months (IQR: 2.8–5.8 months). The high intermixing between sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under cART. After 1 year of cART, there was a minor reduction in proviral π (PreART = 0.20 vs. M12ART = 0.10; P = 0.156) but a significant decrease in HSN (PreART = 0.41 vs. M12ART = 0.25; P = 0.019). We found no correlation between π or HSN at PreART and the rate of HIV DNA decay, T CD4+ counts, or CD4/CD8 ratio at M12ART. Based on a small cohort of Brazilian infected individuals under early cART and analyses of the env region, 1 year of follow-up suggested a reservoir size reduction, allowed a significant decrease of HIV-1 complexity, and achieved immunological restoration regardless of the initial HIV-1 plasma viral load, CD4+ T cell counts, or HIV-1 subtype. However, further studies in the Brazilian setting aiming a longer follow-up and larger cohort are required in this field

Accuracy of a probabilistic record linkage strategy applied to identify deaths among cases reported to the Brazilian AIDS surveillance database

Since record linkage errors can bias measures of disease occurrence and association, it is important to assess their accuracy. The aim of this study is to assess the accuracy of a multiple pass probabilistic record linkage strategy to identify deaths among persons reported to the Brazilian AIDS surveillance database. An HIV/AIDS national surveillance database (N = 559,442) was linked to a total of 6,444,822 deaths registered (all causes) in the Brazilian mortality database. To estimate standard measures of accuracy, we selected all AIDS cases with a date of death registered in the surveillance database from 2002 to 2005 (N = 19,750) and 38,675 cases known to be alive in 2006. The linkage strategy presented a sensitivity of 87.6% (95%CI: 87.1-88.2), a specificity of 99.6% (95%CI: 99.6-99.7), and a positive predictive value of 99.2% (95%CI: 99.1-99.3). We observed a small variation in the validity measures according to some putative predictors of mortality. Our findings suggest that even large and heterogeneous databases can be linked with a satisfactory accuracy

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control

Abstract Background Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes. Results Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were < 1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (< 1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure. Conclusions The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants

Awareness of Prevention Strategies and Willingness to Use Preexposure Prophylaxis in Brazilian Men Who Have Sex With Men Using Apps for Sexual Encounters: Online Cross-Sectional Study

Submitted by Fábio Marques ([email protected]) on 2018-09-06T14:18:22Z No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-09-27T15:12:37Z (GMT) No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5)Made available in DSpace on 2018-09-27T15:12:37Z (GMT). No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilEscola Nacional de Ciências Estatísticas, Rio de Janeiro, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilGeosocial networking (GSN) smartphone apps are becoming the main venue for sexual encounters among Brazilian men who have sex with men (MSM). To address the increased HIV incidence in this population, preexposure prophylaxis (PrEP) was recently implemented in the Brazilian public health system in the context of combined HIV prevention

Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life

The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and >60 years-old, respectively. Older and elderly patients (>40 years) were more likely to have viral suppression than younger patients (18-39 years) (p 0.001). No significant difference in the latest CD4+ T lymphocyte count in the different age strata was observed, although elderly patients (> 50 years) had lower CD4+ T lymphocyte nadir (p 0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDSrelated cancers (p 0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries

Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life

The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and >60 years-old, respectively. Older and elderly patients (>40 years) were more likely to have viral suppression than younger patients (18-39 years) (p 0.001). No significant difference in the latest CD4+ T lymphocyte count in the different age strata was observed, although elderly patients (> 50 years) had lower CD4+ T lymphocyte nadir (p 0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDSrelated cancers (p 0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries

Nelfinavir and Lamivudine pharmacokinetics during the first two weeks of life

Submitted by Sandra Infurna ([email protected]) on 2016-09-20T14:22:27Z No. of bitstreams: 1 jose5_pilotto_etal_IOC_2011.pdf: 318133 bytes, checksum: 3688733dc1e609eddb2d657ed9513dac (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-09-20T14:58:54Z (GMT) No. of bitstreams: 1 jose5_pilotto_etal_IOC_2011.pdf: 318133 bytes, checksum: 3688733dc1e609eddb2d657ed9513dac (MD5)Made available in DSpace on 2016-09-20T14:58:54Z (GMT). No. of bitstreams: 1 jose5_pilotto_etal_IOC_2011.pdf: 318133 bytes, checksum: 3688733dc1e609eddb2d657ed9513dac (MD5) Previous issue date: 2011Boston University School of Medicine. Boston, MA, USA.University of California. David Geffen School of Medicine. Los Angeles, CA, USA.Hospital Geral de Nova Iguaçu. Nova Iguaçu, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.University of California. San Diego School of Medicine. Skaggs School of Pharmacy & Pharmaceutical Sciences. CA, USA.NIH. NICHD. DHHS. Pediatric, Adolescent and Maternal AIDS Branch. Bethesda, MD, USA.University of California. David Geffen School of Medicine. Los Angeles, CA, USA.NIH. NICHD. DHHS. Pediatric, Adolescent and Maternal AIDS Branch. Bethesda, MD, USA.Westat, Inc. Rockville, MD, USA.NIH. NICHD. DHHS. Pediatric, Adolescent and Maternal AIDS Branch. Bethesda, MD, USA.NICHD HPTN 040/PACTG 1043 Protocol teamBackground—There are no previous data describing nelfinavir and lamivudine pharmacokinetics in neonates treated with weight band dosing regimens. Design—Pharmacokinetic study of nelfinavir and lamivudine pharmacokinetics in infants during the first 2 weeks of life treated with weight band dosing regimens. Methods—Intensive 12 hour pharmacokinetic profiles were performed between either days 4–7 or days 10–14 of life in 26 Brazilian infants. Results—Pharmacokinetic data were obtained from 26 infants who received median (range) per kg doses of 58.8 (48.4–79.0) mg/kg for nelfinavir and 2.0 (1.5 – 3.2) mg/kg for lamivudine. Median nelfinavir AUC0-12 was 25.5 (1.7 – 183.5) μg*hr/mL and median C12h was 1.09 (<0.04 – 14.44) μg/mL. AUC0-12 was less than 15 μg*hr/mL (the 10% percentile for adults) in 12 infants (46%). Median lamivudine AUC0-12 was 7.8 (2.7–15.6) μg*hr/mL and median C12h was 0.23 (<0.04 – 0.74) μg/mL. Conclusions—Lamivudine pharmacokinetic parameters observed in this study were consistent with those seen in other studies of neonates. While median nelfinavir AUC and C12h in these neonates were above the exposure targets, interindividual variability in nelfinavir exposure was large and nelfinavir exposure failed to meet the exposure targets in 46% of infants

Characteristics of the Sample Adequacy Control (SAC) in the Cepheid Xpert® CT/NG Assay in Female Urine Specimens

Made available in DSpace on 2015-04-08T14:09:57Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) mariza_morgadoetal_IOC_2014.pdf: 1843908 bytes, checksum: bfc9e7b4bbe85317564c2073d3a1d8a7 (MD5) Previous issue date: 2014University of California. Fielding School of Public Health. Department of Epidemiology. Los Angeles, USA.University of California. David Geffen UCLA School of Medicine. USA.University of California. David Geffen UCLA School of Medicine. USA.University of California. David Geffen UCLA School of Medicine. USA.Hospital Geral de Nova Iguaçu. Nova Iguaçu, RJ, Brazil.Hospital Federal dos Servidores do Estado. Rio de Janeiro, Brazil.University of California. David Geffen UCLA School of Medicine. USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.National Institutes of Health. 4Eunice Kennedy Shriver National Institute of Child Health and Human Development. USA.Background: The Xpert® CT/NG (Cepheid Sunnyvale, CA) is a rapid, fully automated real-time polymerase chain reaction test that simultaneously detects Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). It has high sensitivity and specificity, but also includes a Specimen Adequacy Control (SAC). SAC controls for false negative results by confirming adequate patient sample and appropriate testing conditions. SAC is quantified by its cycle threshold (Ct), the number of cycles required to detect the presence of a single copy human gene. A lower SAC indicates an earlier Ct and more human cellular material detected. Our objectives were to describe the frequency and distribution of SAC Ct values and observe any correlations with detected infections. Methods: Urine samples from 1382 HIV-1-infected pregnant women, collected at the time of labor/delivery underwent Xpert® CT/NG testing. Mean SAC Ct values and standard deviation (SD) were calculated. Student’s t-test was used to compare mean SAC Ct values to a reference of urine samples negative for CT and NG. Results: The urine CT positivity was 17.9% (248/1382) and NG, 4.6% (63/1382). The mean SAC Ct value in urine from women without CT or NG was 28.09 (SD: 4.12) and higher than the mean SAC Ct value for CT positive specimens (27.29, SD: 3.84(P=.0054)), NG positive specimens (26.23, SD: 3.09(P<.0001)), and specimens positive for both CT and NG (26.41, SD: 3.01(P=.0027)). Conclusion: Lower SAC Ct values were significantly associated with chlamydial and gonococcal infections. Further studies should be conducted to determine the utility of SAC Ct values for identifying the presence of increased human cellular material and infectio