Young adults HIV-1 infected by vertical transmission in southern Brazil – Clinical, demographic, and virological features

2017 ◽  
Vol 28 (14) ◽  
pp. 1419-1425
Author(s):  
Beatris M Martin ◽  
Jucélia S Santos ◽  
Fernanda V Scapinello ◽  
Clea EL Ribeiro ◽  
Monica M Gomes-da-Silva ◽  
...  
Keyword(s):  
Disease Progression ◽  
Vertical Transmission ◽  
Venous Blood ◽  
Case Series ◽  
Hiv Disease ◽  
Southern Brazil ◽  
Subtype C ◽  
Viral Subtype ◽  
Hiv 1

Combination antiretroviral therapy promotes longer life expectancy, making it possible for perinatally HIV-infected patients to achieve adulthood. Past therapy was not always optimized, suggesting that virological and host features may also play a role in survival. The aim of this study is to describe characteristics of HIV disease progression associated with virological features in adolescents perinatally that were HIV infected. A case series was conducted including 81 patients that were in follow-up at Hospital de Clínicas/Universidade Federal do Paraná, Curitiba, Brazil. Venous blood was collected to conduct tropism and viral subtype assays. The median age was 19 years old (interquartile range 18–21), and a majority of patients were female (54.3%). Viral subtype was obtained for 66 (82%) patients, and subtypes B and C were found in 34% and 59%, respectively. Tropism assay was conducted in 55 (67%) patients: 71% were R5 and 29% X4. Distribution of viral tropism and subtype shows a significant association of subtype C with R5 tropism. Subtype C is more prevalent in southern Brazil and also in the population infected with HIV by vertical transmission. Both R5 tropism and subtype C are associated with slower progression to AIDS. The survival of these patients may be related to virological features present in a benign pattern of disease progression.

scholarly journals Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Doty B. A. Ojwach ◽  
Daniel MacMillan ◽  
Tarylee Reddy ◽  
Vladimir Novitsky ◽  
Zabrina L. Brumme ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Disease Progression ◽  
Chronic Infection ◽  
Hiv Disease ◽  
Subtype C ◽  
Recombinant Viruses ◽  
Immune Mediated ◽  
Hiv 1

ABSTRACT CD8+ T cell-mediated escape mutations in Gag can reduce HIV-1 replication capacity (RC) and alter disease progression, but less is known about immune-mediated attenuation in other HIV-1 proteins. We generated 487 recombinant viruses encoding RT-integrase from individuals with chronic (n = 406) and recent (n = 81) HIV-1 subtype C infection and measured their in vitro RC using a green fluorescent protein (GFP) reporter T cell assay. In recently infected individuals, reverse transcriptase (RT)-integrase-driven RC correlated significantly with viral load set point (r = 0.25; P = 0.03) and CD4+ T cell decline (P = 0.013). Moreover, significant associations between RT integrase-driven RC and viral load (r = 0.28; P < 0.0001) and CD4+ T cell count (r = −0.29; P < 0.0001) remained in chronic infection. In early HIV infection, host expression of the protective HLA-B*81 allele was associated with lower RC (P = 0.05), as was expression of HLA-B*07 (P = 0.02), suggesting early immune-driven attenuation of RT-integrase by these alleles. In chronic infection, HLA-A*30:09 (in linkage disequilibrium with HLA-B*81) was significantly associated with lower RC (P = 0.05), and all 6 HLA-B alleles with the lowest RC measurements represented protective alleles, consistent with long-term effects of host immune pressures on lowering RT-integrase RC. The polymorphisms V241I, I257V, P272K, and E297K in reverse transcriptase and I201V in integrase, all relatively uncommon polymorphisms occurring in or adjacent to optimally described HLA-restricted cytotoxic T-lymphocyte epitopes, were associated with reduced RC. Together, our data suggest that RT-integrase-driven RC is clinically relevant and provide evidence that immune-driven selection of mutations in RT-integrase can compromise RC. IMPORTANCE Identification of viral mutations that compromise HIV's ability to replicate may aid rational vaccine design. However, while certain escape mutations in Gag have been shown to reduce HIV replication and influence clinical progression, less is known about the consequences of mutations that naturally arise in other HIV proteins. Pol is a highly conserved protein, but the impact of Pol function on HIV disease progression is not well defined. Here, we generated recombinant viruses using the RT-integrase region of Pol derived from HIV-1C-infected individuals with recent and chronic infection and measured their ability to replicate in vitro. We demonstrate that RT-integrase-driven replication ability significantly impacts HIV disease progression. We further show evidence of immune-mediated attenuation in RT-integrase and identify specific polymorphisms in RT-integrase that significantly decrease HIV-1 replication ability, suggesting which Pol epitopes could be explored in vaccine development.

scholarly journals Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

2019 ◽  
Vol 220 (3) ◽  
pp. 432-441 ◽  
Author(s):  
Matt A Price ◽  
Wasima Rida ◽  
William Kilembe ◽  
Etienne Karita ◽  
Mubiana Inambao ◽  
...  
Keyword(s):  
Hla Class I ◽  
Subtype C ◽  
Viral Control ◽  
Viral Loads ◽  
Viral Subtype ◽  
Immunodeficiency Virus ◽  
Time Of Infection ◽  
Subtype A ◽  
Hiv 1

Abstract Few human immunodeficiency virus (HIV)–infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, “viral control”) in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51–2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3–9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3–3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1–2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0–3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines.

scholarly journals Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Stefania Dispinseri ◽  
Mariangela Cavarelli ◽  
Monica Tolazzi ◽  
Anna Maria Plebani ◽  
Marianne Jansson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Antibody Responses ◽  
Viral Escape ◽  
Target Cells ◽  
Transmitted Virus ◽  
Slow Progressors ◽  
Vaccine Antigens ◽  
Kinetics Of ◽  
Hiv 1

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.

scholarly journals Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Luisa Imaz ◽  
Dolors Soy ◽  
Mercé Torra ◽  
Llüisa García-Esteve ◽  
Cristina Soler ◽  
...  
Keyword(s):  
Exclusive Breastfeeding ◽  
Rating Scale ◽  
Venous Blood ◽  
Case Series ◽  
Late Pregnancy ◽  
Structured Interview ◽  
Pharmacokinetic Data ◽  
Close Monitoring ◽  
Young Mania

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice.Objectives: To present clinical and pharmacokinetic data of nine mother–infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006–2018).Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother–infant pairs at delivery, and at days 1–5, 7–11, 30, and 60 postpartum, and monthly until 6-months.Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02–1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum.Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.

Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression

Vaccine ◽  
2002 ◽  
Vol 20 (17-18) ◽  
pp. 2343-2347 ◽  
Author(s):  
Catharina E.A. Lindenburg ◽  
Ineke Stolte ◽  
Miranda W. Langendam ◽  
Frank Miedema ◽  
Ian G. Williams ◽  
...  
Keyword(s):  
Disease Progression ◽  
Therapeutic Vaccination ◽  
Virus Like Particles ◽  
Long Term Follow Up ◽  
Hiv 1

scholarly journals Cerebrovascular fibromuscular dysplasia

2017 ◽  
Vol 7 (3) ◽  
pp. 225-236 ◽  
Author(s):  
Andrea M. Harriott ◽  
Eli Zimmerman ◽  
Aneesh B. Singhal ◽  
Michael R. Jaff ◽  
Mark E. Lindsay ◽  
...  
Keyword(s):  
Disease Progression ◽  
Fibromuscular Dysplasia ◽  
Massachusetts General Hospital ◽  
Case Series ◽  
Antiplatelet Agents ◽  
Cerebrovascular Event ◽  
Symptomatic Disease ◽  
Surveillance Imaging ◽  
History Of

AbstractBackground:Fibromuscular dysplasia (FMD) is a rare noninflammatory, nonatherosclerotic arteriopathy of medium-sized arteries affecting up to 7% of the population. The disease can affect any artery but commonly affects renal, extracranial carotid, and vertebral arteries. The epidemiology and natural course of cerebrovascular FMD is unknown and requires further investigation.Methods:We present demographic and outcomes data on a case series of 81 patients with cerebrovascular FMD from Massachusetts General Hospital presenting between 2011 and 2015 followed by a review of the peer-reviewed literature.Results:Patients were a median age of 53 years (±12 SD) and the majority were women. Approximately 50% had a history of tobacco use and more than two-thirds had hypertension. Most patients were on monoplatelet therapy with aspirin; during follow-up, 7 of 67 had progressive disease or additional symptoms. One of 67 patients had a cerebrovascular event: TIA. There were 5 of 67 who had noncerebrovascular events or disease progression and 1 death of unclear cause.Conclusions:Cerebrovascular FMD may present with myriad symptoms. Our data support that patients with FMD with symptomatic disease have a low rate of recurrent symptoms or disease progression and can be managed conservatively with stroke risk modification, antiplatelet agents, surveillance imaging, and counseling.

scholarly journals Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in a region of Southern Brazil where the subtype C of HIV-1 infection predominates

2011 ◽  
Vol 15 (4) ◽  
pp. 349-355 ◽  
Author(s):  
Sandra Aparecida Manenti ◽  
João Galato Júnior ◽  
Elizângela da Silva Silveira ◽  
Roberto Teixeira Oenning ◽  
Priscyla Waleska Targino de Azevedo Simões ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Clinical Characteristics ◽  
Southern Brazil ◽  
Subtype C ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Hiv Aids

scholarly journals A17 The effect of intra-host evolution of HIV-2 capsid on disease progression

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
M T Boswell ◽  
A Palm ◽  
S Karlson ◽  
F Månsson ◽  
H Norrgren ◽  
...  
Keyword(s):  
West Africa ◽  
Disease Progression ◽  
Conformational Changes ◽  
Horizontal Transmission ◽  
Evolutionary Rates ◽  
Survival Times ◽  
Infected People ◽  
Viral Loads ◽  
Hiv 1

Abstract The human immunodeficiency virus type 2 (HIV-2) is an important cause of acquired immune deficiency syndrome (AIDS) in West Africa. The virus started circulating in humans around 1938 and has spread predominantly within West Africa with an estimated 1–2 million people being infected today. Compared with the pandemic HIV-1, HIV-2 infected people have longer AIDS-free survival times, higher CD4+ counts and lower risk of vertical and horizontal transmission. Approximately 35 per cent of HIV-2 infected individuals are classified as so-called long-term non-progressors with undetectable viral loads and limited disease progression after 10 years of follow-up. It has been shown that HIV-2 is more sensitive to the host restriction factor TRIM5α when compared with HIV-1, and this has been linked to conformational changes in the retroviral capsid. TRIM5α binds at the interface between three capsid hexamers, initiates early uncoating and proteasomal degradation. TRIM5 genotype has shown only modest effects on HIV-1 disease outcomes. HIV-2 capsid sequences bearing a specific poly-proline motif have been associated with lower viral loads and presentation of protective HLA I-restricted epitopes. The major aims of this study were to (1) determine HIV-2 capsid intra-host evolutionary rates and (2) identify residues that are affected by positive selection and that can be linked to HIV-2 viral load and disease progression in conjunction with TRIM5 genotype. The Guinea-Bissau Police cohort is unique, with decades of relatively frequent follow-up. One hundred and sixty-five patients were included for genotyping of TRIM5, 62 females and 103 males. Median age at enrolment was 52.6 years (range 30–87) and 7.9 per cent of patients had a CD4 percentage < 15 per cent at enrolment. Six of these individuals were included for amplification of HIV-2 capsid from longitudinally collected samples. Viral RNA was extracted from stored blood plasma samples and capsid of the circulating viral quasispecies was amplified, cloned, and sequenced, as previously described. Bayesian analysis will be used to determine intra-host evolutionary rates, dN/dS ratios and how these parameters associate with disease progression and TRIM5 genotype.

scholarly journals Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS in a region of Southern Brazil where the subtype C of HIV-1 infection predominates

2011 ◽  
Vol 15 (4) ◽  
pp. 349-355 ◽  
Author(s):  
Sandra Aparecida Manenti ◽  
João Galato Júnior ◽  
Elizângela da Silva Silveira ◽  
Roberto Teixeira Oenning ◽  
Priscyla Waleska Targino de Azevedo Simões ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Clinical Characteristics ◽  
Southern Brazil ◽  
Subtype C ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Hiv Aids

scholarly journals Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana

2016 ◽  
Vol 115 (12) ◽  
pp. 2114-2121 ◽  
Author(s):  
S. S. Martinez ◽  
A. Campa ◽  
H. Bussmann ◽  
S. Moyo ◽  
J. Makhema ◽  
...  
Keyword(s):  
Cell Count ◽  
Disease Progression ◽  
Fat Mass ◽  
Antiretroviral Treatment ◽  
Obesity Paradox ◽  
Hiv Disease ◽  
Time To Event ◽  
Cd4 Cell Count ◽  
Cd4 Cell

AbstractAn obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0–24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

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