A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation.
Ontology highlight
ABSTRACT:
SUBMITTER: Violari A
PROVIDER: S-EPMC6345921 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation.
Violari Avy A Cotton Mark F MF Kuhn Louise L Schramm Diana B DB Paximadis Maria M Loubser Shayne S Shalekoff Sharon S Da Costa Dias Bianca B Otwombe Kennedy K Liberty Afaaf A McIntyre James J Babiker Abdel A Gibb Diana D Tiemessen Caroline T CT
Nature communications 20190124 1
Understanding HIV remission in rare individuals who initiated antiretroviral therapy (ART) soon after infection and then discontinued, may inform HIV cure interventions. Here we describe features of virus and host of a perinatally HIV-1 infected child with long-term sustained virological control. The child received early limited ART in the Children with HIV Early antiRetroviral therapy (CHER) trial. At age 9.5 years, diagnostic tests for HIV are negative and the child has characteristics similar ...[more]
Similar Datasets
Project description:ObjectivesPlanned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial.MethodsPost-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time.ResultsIn all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub-study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post-trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT - PTI) = -0.15; 95% CI: -0.34-0.05), P = 0.14]. The sub-study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells.ConclusionsChildren tolerated PTI with few long-term clinical, virological or immunological consequences.
| S-EPMC8436743 | biostudies-literature
Project description:The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as "Not Evaluable" due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.
| S-EPMC5298215 | biostudies-literature
Project description:ObjectiveThis study aims to analyze the efficacy of anti-syphilis treatment and the impact of syphilis events on HIV virology and immunology in HIV/syphilis co-infected patients on long-term antiretroviral therapy (ART) and to investigate the incidence and factors of syphilis recurrence/re-infection/serofast state. The insights derived from this investigation can potentially guide strategies for preventing and managing syphilis and AIDS.MethodsA retrospective case-control study was conducted at the AIDS clinic of Peking Union Medical College Hospital from January 2003 to December 2022. The study involved 86 HIV/syphilis co-infected patients and 86 HIV mono-infected patients matched based on age, baseline CD4 + T cell counts, and viral load. We examined the clinical characteristics of HIV/syphilis co-infected patients, evaluated the efficacy of anti-syphilis treatment, and analyzed the dynamic changes in HIV virology and immunology. The Generalized Estimating Equations (GEE) model investigated the factors associated with HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state.ResultsSyphilis serofast state was observed in 11.6% (10/86) of HIV/syphilis co-infected patients after treatment, and 33.7% (29/86) had syphilis recurrence or re-infection. The overall effectiveness of syphilis treatment stood at 76.8% (63/82). Notably, the effectiveness of syphilis treatment displayed a significant correlation with baseline syphilis titers exceeding 1:128 (p = 0.003). Over the 10-year follow-up period on ART, the HLA-DR + CD8+/CD8 + % levels in the HIV/syphilis co-infected group were markedly higher than those in the HIV mono-infected group (p < 0.05). However, no significant differences were observed between the two groups regarding HIV viral load, CD4+ T cell counts, CD8+ T cell counts, CD4/CD8 ratio, and CD38 + CD8+/CD8 + % (p > 0.05). GEE analysis model revealed that elevated HLA-DR + CD8+/CD8 + % levels were associated with HIV/syphilis co-infection (OR = 1.026, 95% CI = 1.007-1.046; p = 0.007) and syphilis recurrence/reinfection/serofast state (OR = 1.036, 95% CI = 1.008-1.065; p = 0.012).ConclusionWhile HIV/syphilis co-infected patients typically receive adequate treatment, the incidence of syphilis recurrence and reinfection remain notably elevated. A heightened HLA-DR + CD8+/CD8+ % is a notable risk factor for HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state. Therefore, it is advisable to reinforce health education efforts and ensure regular follow-ups for people living with HIV undergoing ART to monitor syphilis infection or increased risk of syphilis infection.
| S-EPMC10823526 | biostudies-literature
Project description:BackgroundThere is very little data on long-term immune recovery responses in patients on suppressive antiretroviral therapy (ART) in the setting of sub-Saharan Africa (SSA). Thus, we sought to determine CD4+ T-cell, CD8+ T-cell and CD4/CD8 ratio responses in a cohort of HIV infected individuals on sustained suppressive ART followed up for more than a decade.MethodsThe cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 14 years. Trends in median CD4+ T-cells, CD8+ T-cells and CD4/CD8 ratio were reviewed retrospectively. Poisson regression models were used to identify factors associated with achieving normalized T-cell biomarkers. Kaplan-Meier curves were used to estimate the probability of attaining normalized counts while on suppressive ART.ResultsA total of 227 patients with a median duration of follow-up on ART of 12 (IQR: 10.5-13.0) years were included. CD4 cell count increased from baseline median of 138 cells (IQR: 70-202) to 555 cells (IQR: 417-830). CD4 cell increased continuously up until 5 years, after which it plateaued up until 14 years of follow up. Only 69.6% normalized their CD4 cell count within a median of 6.5 (IQR: 3.0-10.5) years. In addition, only 15.9% of the cohort were able to achieve the median reference CD4+ T-cell threshold count in Ethiopians (≈760 cells/μL). CD8+ T-cell counts increased initially until year 1, after which continuous decrease was ascertained. CD4/CD8 ratio trend revealed continuous increase throughout the course of ART, and increased from a median baseline of 0.14 (IQR: 0.09-0.22) to a median of 0.70 (IQR: 0.42-0.95). However, only 12.3% normalized their ratio (≥ 1.0) after a median of 11.5 years. In addition, only 8.8% of the cohort were able to achieve the median reference ratio of healthy Ethiopians.ConclusionDetermination of both CD4+ and CD8+ T-cells, along with CD4/CD8 ratio is highly relevant in long-term follow-up of patients to assess immune recovery. Monitoring ratio levels may serve as a better biomarker risk for disease progression among patients on long-term ART. In addition, the findings emphasize the relevance of initiation of ART at the early stage of HIV-1 infection.
| S-EPMC7580989 | biostudies-literature
Project description:Several studies have reported the persistence of HCV RNA in liver and/or peripheral blood mononuclear cells (PBMCs) in spite of undetectable viremia in patients who have achieved sustained virological response (SVR). This event, defined as occult HCV infection, remains controversial and low titers of persistent virus may be underestimated because it has not yet been analyzed by a highly sensitive test such as droplet digital PCR (ddPCR). This method provides an alternate ultra-sensitive detection technique for very low numbers of copies of viral RNA or DNA. The aim of this study was to evaluate the persistence of HCV in HIV-coinfected patients with long-term SVR using ddPCR. For each patient, the presence of HCV RNA in serum and PBMCs at baseline was determined by nested RT-ddPCR. Patients with HCV RNA in PBMCs at baseline were followed until the end of the study. One hundred and twenty-three patients were analyzed for persistence of HCV RNA in serum and PBMCs. Persistence of HCV was not found in serum in any patient. HCV RNA was detected in PBMCs in one patient (0.81%; 95% CI: 0.04-3.94) and resolved spontaneously during follow-up. Persistence of HCV RNA in PBMCs is not a common event in HIV/HCV co-infected patients with long-term SVR evaluated by RT-ddPCR.
| S-EPMC6715682 | biostudies-literature
Project description:Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
| S-EPMC3597518 | biostudies-other
Project description:BackgroundAlthough WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring.Methods and findingsIn the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks). Overall, 67 (6%) switched to second-line ART and 54 (4%) died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 counts versus 297/375 (79%) without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI -3.4% to +8.0%]; P = 0.43), with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post-week 24 was spent with persistent low-level viraemia (80-5,000 copies/ml) and 10% with VL rebound ?5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ?5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5) additional NRTI mutation accumulated over 2 years' rebound. Nineteen out of 48 (40%) VLs 1,000-5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11%) VLs ?5,000 copies/ml resuppressed (P < 0.0001). Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes.ConclusionsIn this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ?5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.Trial registrationISRCTN Registry, ISRCTN24791884.
| S-EPMC5685482 | biostudies-literature
Project description:BACKGROUND:Although the short-term benefits of a sustained virological response (SVR) to interferon-based therapies of chronic hepatitis C (CHC) are well known, the long-term consequences of SVR are less clear. AIM:To assess changes in markers of disease activity and fibrosis in patients followed up to 23 years post-SVR. METHODS:The first 103 SVR patients (from 1984 to 2003) at the National Institutes of Health Clinical Center were evaluated. Serum markers before treatment and at the last visit were compared. Evaluations after 2007 included transient elastography (TE). RESULTS:Of 103 patients, three subsequently relapsed 0.7, 6.3 and 6.5 years post therapy. The remaining 100 patients (56 men, mean age 56 years) maintained SVR at final follow-up. No patients developed hepatic decompensation, but one with pre-treatment cirrhosis died 12 years post SVR of hepatocellular carcinoma. In comparison to pre-treatment values, markers improved at follow-up, including mean ALT (152-27 U/L), AST (87-24 U/L), alkaline phosphatase (78-69 U/L), IgG (1463-1113 mg/dL), platelet count (209 000-239 000/?L) and AST to platelet count ratio index (APRI: 1.31-0.33). TE was performed in 69 patients and was normal (<7.0 kPA) in 60%, moderately elevated (7.1-13.8) in 31% and cirrhotic range (>13.8) in 9%. TE and platelet counts at follow-up correlated with fibrosis on pre-treatment liver biopsy (P < 0.001). CONCLUSIONS:In 97% of patients with CHC, SVR is durable without evidence of disease progression, although some degree of hepatic fibrosis may persist and patients with pre-treatment cirrhosis are at continuing low risk for hepatocellular carcinoma.
| S-EPMC3627475 | biostudies-literature
Project description:ObjectiveTo study the long-term clinical, immunological and virological outcomes among people living with HIV on antiretroviral therapy (ART) in Myanmar.MethodsA retrospective analysis of people on ART for >9 years followed by a cross-sectional survey among the patients in this group who remained on ART at the time of the survey. Routinely collected medical data established the baseline clinical and demographic characteristics for adult patients initiating ART between 2004 and 2006. Patients remaining on ART between March-August 2015 were invited to participate in a survey assessing clinical, virological, immunological, and biochemical characteristics.ResultsOf 615 patients included in the retrospective analysis, 35 (6%) were lost-to-follow-up, 9 (1%) were transferred, 153 died (25%) and 418 (68%) remained active in care. Among deaths, 48 (31.4%) occurred within 3 months of ART initiation, and 81 (52.9%) within 12 months, 90.1% (n = 73) of which were initially classified as stage 3/4. Of 385 patients included in the survey, 30 (7.7%) were on second-line ART regimen; 373 (96.8%) had suppressed viral load (<250 copies/ml). The mean CD4 count was 548 cells/ mm3 (SD 234.1) after ≥9 years on treatment regardless of the CD4 group at initiation. Tuberculosis while on ART was diagnosed in 187 (48.5%); 29 (7.6%) had evidence of hepatitis B and 53 (13.9%) of hepatitis C infection.ConclusionsAppropriate immunological and virological outcomes were seen among patients on ART for ≥9 years. However, for the complete initiating cohort, high mortality was observed, especially in the first year on ART. Concerning co-infections, tuberculosis and viral hepatitis were common among this population. Our results demonstrate that good long-term outcomes are possible even for patients with advanced AIDS at ART initiation.
| S-EPMC5805251 | biostudies-literature
Project description:Suppressive antiretroviral therapy (ART) substantially decreases HIV transmission in clinical research settings. We sought to measure the frequency and correlates of periods of transmission risk among individuals taking ART during multiple years of observation in rural, southwestern Uganda.Observational cohort study.We collected sexual behavior and viral load data in a Ugandan cohort of people living with HIV/AIDS from the time of ART initiation. We defined each 90-day visit as a potential transmission period if HIV-1 RNA was more than 400?copies/ml and the participant reported sexual transmission risk behavior, defined as unprotected sexual contact with at least 1 HIV-uninfected partners or partners of unknown serostatus in the prior 90 days.We evaluated data from 463 individuals on ART over a median 3.5 years of observation and 5293 total study visits. During that time, over half (259, 56%) had detectable viremia or reported sexual transmission risk behavior at least once. However, only 23 (5%) had both simultaneously, at 28 (<1%) of all visits. Transmission sexual behavior was reported at 6% of visits with detectable viremia. In multivariable regression modeling, correlates of transmission risk periods included younger age, lower CD4 cell count, low household asset ownership and increased internalized stigma.Although detectable viremia and/or sexual transmission risk behavior occurred in over half of individuals, ART reduced periods of HIV transmission risk by over 90% during up to 6 years of observation time. These findings provide further support for provision of ART, along with interventions to promote long-term adherence, to reduce HIV transmission in HIV-endemic settings.
| S-EPMC4038415 | biostudies-literature