Format
Sort by
Items per page

Send to

Choose Destination

Selected items

Items: 12

1.
AIDS. 2018 Dec 19. doi: 10.1097/QAD.0000000000002101. [Epub ahead of print]

Associations between baseline biomarkers and lung function in HIV-positive individuals.

Author information

1
Minneapolis VA Health Care System, Minneapolis/USA.
2
University of Minnesota, Minneapolis/USA.
3
D.M. MacDonald and A.D. Zanotto shared co-primary author responsibilities.
4
Hennepin Country Medical Center, Minneapolis/USA.
5
Institution of EMC Instytut Medyczny SA, Wroclaw/Poland.
6
IDEAA Foundation, Buenos Aires/Argentina.
7
Virginia Commonwealth University, Richmond/USA.
8
Evangelismos General Hospital, Athens/Greece.
9
Desmond Tutu HIV Foundation, Cape Town/South Africa.

Abstract

OBJECTIVE:

To analyze the association of baseline biomarker data with cross sectional lung function and subsequent decline in lung function in HIV-positive persons.

DESIGN:

Lung function was modeled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses we restricted to those participants with at least one good-quality follow up spirometry test.

METHODS:

We performed linear regression of baseline FEV1, FVC, and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts, and baseline HIV-RNA. Biomarkers included D-dimer, hsCRP, IL-6, IL-27, serum amyloid A, sICAM-1, sVCAM-1, albumin, and total bilirubin.

RESULTS:

Among 903 included participants, baseline median age was 36 years, CD4 count was 647 cells/mm, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6, and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3,293 spirometry-years of follow up).

CONCLUSIONS:

Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4+ T-cell counts >500 cells/mm.

2.
AIDS Res Hum Retroviruses. 2019 Jan 2. doi: 10.1089/AID.2018.0176. [Epub ahead of print]

Therapeutic immunisation benefits mucosal-associated invariant T-cell recovery in contrast to IL-2, GM-CSF, and rhGH addition in HIV-1+ treated patients: individual case reports from phase I trial.

Author information

1
Imperial College London, Department of Medicine , Centre for Immunology and Vaccinology , Chelsea and Westminster Hospital , 369 Fulham Road , London, United Kingdom of Great Britain and Northern Ireland , SW10 9NH ; a.cocker15@imperial.ac.uk.
2
Imperial College London, Department of Medicine, London, United Kingdom of Great Britain and Northern Ireland ; louise.greathead@nhs.net.
3
Imperial College London, Department of Medicine, London, United Kingdom of Great Britain and Northern Ireland ; annaherasimtschuk@gmail.com.
4
Imperial College London, Department of Medicine , Chelsea and Westminster Hospital , 369 Fulham Road , London , London, United Kingdom of Great Britain and Northern Ireland , SW10 9NH ; s.mandalia@imperial.ac.uk.
5
Imperial College London, Department of Medicine, London, United Kingdom of Great Britain and Northern Ireland ; p.kelleher@imperial.ac.uk.
6
Imperial College London, Department of Medicine, London, United Kingdom of Great Britain and Northern Ireland ; n.imami@imperial.ac.uk.

Abstract

MAIT cell populations are reduced in frequency in HIV-1+ patients, and this disruption is associated with systemic immune activation. Reconstitution of MAIT frequency may benefit HIV-1 infected individuals, however only recently has in vivo work been endeavoured. Treatment with IL-2, GM-CSF and rhGH immunotherapy combined with an HIV-1 vaccine in the context of ART has shown to reconstitute CD4 T-cell population numbers and function. In this study cryopreserved peripheral blood mononuclear cells (PBMC) from 12 HIV-1+ patients who were undergoing a combination of HIV-1 vaccine and/or IL-2, GM-CSF and rhGH immunotherapy in conjunction with ART were analysed to assess the potential of this treatment to promote MAIT cell proliferation. PBMC were thawed from study baseline, week 2 and week 48 time-points, fluorescently stained for MAIT cell markers and assessed by flow cytometric analysis. Matched pairs and inter-group results were statistically compared using appropriate methods. MAIT cell frequency was increased from baseline at 48 weeks in participants who received vaccine only, whereas individuals receiving IL-2, GM-CSF and rhGH immunotherapy with or without vaccine did not show additional benefit. Whilst IL-2, GM-CSF and rhGH treatment promotes CD4 T-cell reconstitution and HIV-1-specific T-cell function, it does not support MAIT cell recovery in patients on suppressive ART. Therapeutic immunisation however has a positive effect, highlighting the importance of aiming for balanced promotion of T-cell population reconstitution to impact on HIV-1 transmission and pathogenesis.

3.
AIDS Res Hum Retroviruses. 2019 Jan 2. doi: 10.1089/AID.2018.0154. [Epub ahead of print]

Mucosal susceptibility to HIV infection in the proliferative and secretory phases of the menstrual cycle.

Author information

1
Population Council, CBR, New York, New York, United States ; gcalenda@popcouncil.org.
2
Population Council, CBR, New York, New York, United States ; gvillegas@popcouncil.org.
3
Icahn School of Medicine at Mount Sinai, Obstetrics and Gynecology, New York, United States ; alexandra.e.reis@gmail.com.
4
Icahn School of Medicine at Mount Sinai, Obstetrics and Gynecology, New York, United States ; lpos119@gmail.com.
5
Population Council, CBR, New York, New York, United States ; pbarnable@popcouncil.org.
6
Population Council, CBR, New York, New York, United States ; lmamkina@yahoo.com.
7
Population Council, CBR, New York, New York, United States ; nkumar@popcouncil.org.
8
Population Council, CBR, New York, New York, United States ; kroberts@popcouncil.org.
9
Icahn School of Medicine at Mount Sinai, Pathology, New York, United States ; Tamara.Kalir@mountsinai.org.
10
Population Council, CBR, New York, New York, United States ; emartinelli@popcouncil.org.
11
Icahn School of Medicine at Mount Sinai, Obstetrics and Gynecology, New York, United States ; Rhoda.Sperling@mssm.edu.
12
Population Council, CBR, New York, New York, United States ; nteleshova@popcouncil.org.

Abstract

Factors underlying HIV acquisition in women remain incompletely understood. This study evaluated ex vivo mucosal HIV-1BaL infection (ectocervix, endocervix), T cell frequencies and phenotype (ectocervix, endocervix, peripheral blood) and HIV-1BaL-induced tissue immune responses (ectocervix) in the proliferative and secretory phases of the menstrual cycle using samples obtained from women undergoing hysterectomies. Tissue infectivity (number of productively infected explants) and infection level following 500 and/or 50 TCID50 HIV-1BaL challenge were similar in the proliferative and secretory phases. Although not associated with infection outcomes, higher frequencies of HIV target CD4+47+ T cells and stronger HIV-1BaL-induced pro-inflammatory responses were detected in ectocervix in secretory vs. proliferative phase. Independently of the cycle phase, serum E2 concentrations were inversely associated with ectocervical and endocervical tissue infection levels following high dose 500 TCID50 HIV-1BaL challenge, with frequencies of CD4+47+ T cells in endocervix, and with HIV-induced IL2R and IL4 in ectocervix. Although serum P4 concentrations and P4/E2 ratios were neither associated with tissue infection level nor infectivity, high P4 concentrations and/or P4/E2 ratios correlated with high frequencies of CD4+47+ T cells in ectocervix, low frequencies of CD4+CD103+ blood T cells, low CD4+LFA-1+ T cells in endocervix, and pro-inflammatory (IL1, IL17, TNF) ectocervical tissue responses to HIV-1BaL. The data suggest an inhibitory effect of E2 on mucosal HIV infection, provide insights into potential mechanisms of E2-mediated anti-HIV activity, and highlight P4-associated immune changes in the mucosa.

4.
Clin Infect Dis. 2019 Jan 2. doi: 10.1093/cid/ciy1123. [Epub ahead of print]

Residual or recurrent precancerous lesions after treatment of cervical lesions in HIV-infected women: a systematic review and meta-analysis of treatment failure.

Author information

1
CEPED, Institut de Recherche pour le Développement, Université Paris Descartes, Paris, France.
2
Recherche - Santé & Développement, Yaoundé, Cameroon.
3
Department of Gynecology, CHU of Yaoundé, Yaoundé, Cameroon.
4
Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Cameroon.
5
Interstates School of Public Heath in Central Africa, Congo, Brazzaville.
6
International Agency for Research on Cancer, Lyon, France.

Abstract

Background:

Screening and treating premalignant cervical lesions (CIN2+) is an effective way to prevent cervical cancer, and recommendations exist for monitoring of treatment success. Yet, there is no specific recommendation for HIV-infected women, who are at known increased risk of cervical cancer.

Methods:

A systematic review was performed by searching MEDLINE, EMBASE and Web of Science from January 1980 through May 2018. Eligible studies described prevalence of histologically and/or cytologically-defined lesions in HIV-infected women, at least 6 months post-treatment. Primary endpoint was treatment failure, defined as the presence of residual and/or recurrent high-grade CIN2+/HSIL+ lesions post-treatment. Pooled prevalence in HIV-infected women, and odds ratios (OR) for HIV-infected compared to HIV-uninfected women were estimated using random-effects models.

Results:

Among 40 eligible studies, pooled prevalence of treatment failure in HIV-infected women was 21.4% (95%CI 15.8-27.0). There was no significant difference in treatment failure for cryotherapy (13.9%, 95%CI 6.1-21.6) versus LEEP (13.8%, 95%CI 8.9-18.7,p=0.9), but it was significantly higher in women with positive (47.2%, 95%CI 22.0-74.0) than with negative (19.4%, 95%CI 11.8-30.2) margins (OR 3.4, 95%CI 1.5-7.7). Treatment failure was significantly increased in HIV-infected versus HIV-uninfected women, both overall (OR 2.7, 95%CI 2.0-3.5) and in all sub-group analyses.

Conclusion:

There is strong evidence for increased risk of treatment failure in HIV-infected women in comparison to their HIV-negative counterparts. The only significant predictor of treatment failure in HIV-infected women was positive margin status, but further data is needed on long-term outcomes after ablative treatment in HIV-infected women.

5.
Clin Infect Dis. 2019 Jan 2. doi: 10.1093/cid/ciy1132. [Epub ahead of print]

Dolutegravir monotherapy versus dolutegravir/abacavir/lamivudine for virologically suppressed people living with chronic HIV infection: the randomized non-inferiority MONCAY trial.

Author information

1
Service des Maladies Infectieuses et Tropicales, CHR d'Orléans - La Source, Orléans, France.
2
Service des Maladies Infectieuses, CHU Hôtel Dieu and INSERM UIC 1413 Nantes University, Nantes, France.
3
Service des Maladies Infectieuses, CHU Bretonneau, Tours, France.
4
Service des Maladies Infectieuses et Tropicales, CHG de Niort, Niort, France.
5
Service des Maladies Infectieuses, CHD de Vendée, La Roche-sur-Yon, France.
6
Le Trait d'Union, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
7
Service des Maladies Infectieuses, CHU La Milétrie, Poitiers, France.
8
Service des Maladies Infectieuses, Groupe Hospitalier de La Rochelle - Ré - Aunis, La Rochelle, France.
9
Service des Maladies Infectieuses, CHRU-Brabois, Nancy, France.
10
Département d'Informatique Médicale, CHR d'Orléans - La Source, Orléans, France.
11
Laboratoire de Microbiologie clinique, CHU Necker and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
12
Unité de Biostatistique et de Recherche Clinique, CHU de Caen; EA2656 Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université Caen Normandie, Caen, France.

Abstract

BACKGROUND:

We investigated whether dolutegravir monotherapy was able to maintain virological suppression in people living with HIV on a successful dolutegravir-based triple-therapy.

METHODS:

MONCAY was a 48-week multicentric, randomized, open-label, 12% non-inferiority margin trial. Patients with CD4 nadir>100/μL, plasma HIV-1 RNA <50 copies/mL for ≥12 months and stable regimen with dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week (W) 24 in intention-to-treat (ITT) snapshot analysis. Virologic failure (VF) was defined as two consecutive HIV-RNA >50 copies/mL within 2 weeks apart.

RESULTS:

Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By W24, two patients in DTG group experienced VF without resistance to the INSTI class; one patient discontinued DTG/ABC/3TC due to adverse event. The success rate at W24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm; difference 2.7%, 95% CI: -5.0 to 10.8. During subsequent follow-up, five additional VF occurred in the DTG arm (two of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at W48 was 9.7% (95% CI: 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (p=0.005, by the log-rank test). The DSMB recommended to re-intensify the DTG arm with standardized triple-therapy.

CONCLUSIONS:

Because the risk of virological failure with resistance increases overtime, we recommend avoiding dolutegravir monotherapy as a maintenance strategy among people living with chronic HIV infection.

6.
Clin Infect Dis. 2019 Jan 2. doi: 10.1093/cid/ciy1131. [Epub ahead of print]

Non-inferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: a randomized, controlled, multi-site, open-label, non-inferiority trial.

Author information

1
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
2
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
3
Service of Clinical Pharmacology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.
4
Center of Infectious Diseases Zurich, Zurich, Switzerland.
5
Checkpoint Zurich, Zurich, Switzerland.
6
Institute of Global Health, University of Geneva, Switzerland.

Abstract

Background:

Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy.

Methods:

EARLY-SIMPLIFIED is a randomized, open label, non-inferiority trial. Patients who started cART <180 days after estimated date of a documented primary HIV-1 infection and had a HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once-daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; non-inferiority margin 10%.

Results:

Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 32/32 (100%) in the cART group (difference 0.00%, 95%-CI [-100%, 4.76%]). This showed non-inferiority of the dolutegravir monotherapy at the pre-specified level.

Conclusion:

In this pilot study consisting of patients who initiated cART <180 days after the estimated day of a documented primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was non-inferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART.

7.
Clin Infect Dis. 2019 Jan 2. doi: 10.1093/cid/ciy1136. [Epub ahead of print]

Antiretroviral monotherapy for HIV. Game over or future perspectives?

Author information

1
Erasmus MC, Section of infectious Diseases, Rotterdam, the Netherlands.
9.
J Infect Dis. 2019 Jan 2. doi: 10.1093/infdis/jiy747. [Epub ahead of print]

High resolution evolutionary analysis of within-host hepatitis C virus infection.

Author information

1
Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
2
Department of Statistics, University of Oxford, Oxford, United Kingdom.
3
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
4
Department of Zoology, University of Oxford, Oxford, United Kingdom.

Abstract

Background:

Despite the recent breakthroughs in the treatment of HCV infection, we have a limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap is important for identifying the main sources of disease transmission and for evaluating the risk of drug-resistance mutations emerging and disseminating in a population.

Method:

We have undertaken a high-resolution analysis of HCV within-host evolution from four individuals co-infected with HIV. We used long-read, deep-sequenced data of the full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics.

Results:

We found statistical support for population structure maintaining the within-host HCV genetic diversity in three out of four individuals. We also report the first population genetic estimate of the within-host recombination rate for HCV (0.28x10 -7 recombination/site/year), which is considerably lower than that estimated for HIV-1 and the overall nucleotide substitution rate estimated during HCV infection.

Conclusion:

Together, these observations indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.

10.
J Virol. 2019 Jan 2. pii: JVI.01832-18. doi: 10.1128/JVI.01832-18. [Epub ahead of print]

HIV subtype and Nef-mediated immune evasion function correlate with viral reservoir size in early-treated individuals.

Author information

1
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
2
Department of Medicine, University of Toronto, Toronto, ON, Canada.
3
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
4
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
5
Johns Hopkins University, Baltimore, MD, USA.
6
Maple Leaf Clinic, Toronto ON, Canada.
7
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
8
Department of Medicine, University of Toronto, Toronto, ON, Canada zbrumme@sfu.ca mario.ostrowski@gmail.com.
9
Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada.
10
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada zbrumme@sfu.ca mario.ostrowski@gmail.com.

Abstract

The HIV accessory protein Nef modulates key immune evasion and pathogenic functions and its encoding gene region exhibits high sequence diversity. Given the recent identification of early HIV-specific adaptive immune responses as novel correlates of HIV reservoir size, we hypothesized that viral factors that facilitate evasion of such responses - namely, Nef genetic and functional diversity - might also influence reservoir establishment and/or persistence. We isolated baseline plasma HIV RNA-derived nef clones from 30 acute/early-infected individuals who participated in a clinical trial of early cART (<6 months following infection) and assessed each Nef clone's ability to downregulate CD4 and HLA class I in vitro We then explored the relationships between baseline clinical, immunologic and virologic characteristics, and HIV reservoir size measured 48 weeks following initiation of suppressive cART (where reservoir size was quantified in terms of proviral DNA loads as well as levels of replication-competent HIV in CD4+ T-cells). Maximal within-host Nef-mediated downregulation of HLA, but not CD4, correlated positively with post-cART proviral DNA levels (Spearman's R=0.61; p=0.0004) and replication-competent reservoir sizes (Spearman's R=0.36; p=0.056) in univariable analyses. Furthermore, Nef-mediated HLA downregulation function was retained in final multivariable models adjusting for established clinical and immunologic correlates of reservoir size. Finally, HIV subtype B infected persons (N=25) harbored significantly larger viral reservoirs compared to non-B infected persons (2 CRF01_AE and 3 subtype G infections). Our results highlight a potentially important role of viral factors - in particular HIV subtype and accessory protein function - in modulating viral reservoir establishment and persistence.IMPORTANCE While combination antiretroviral therapies (cART) have transformed HIV into a chronic manageable condition, they do not act upon the latent HIV reservoir and are therefore not curative. As HIV cure or remission should be more readily achievable in individuals with smaller HIV reservoirs, achieving a deeper understanding of clinical, immunologic and virologic determinants of reservoir size is critical to eradication efforts. We performed a post-hoc analysis of 30 participants of a clinical trial of early cART who had previously been assessed in detail for their clinical, immunologic and reservoir size characteristics. We observed that HIV subtype and autologous Nef-mediated HLA downregulation function correlated with viral reservoir size measured approximately one year post-cART initiation. Our findings highlight virologic characteristics - both genetic and functional - as possible novel determinants of HIV reservoir establishment and persistence.

11.
N Engl J Med. 2019 Jan 3;380(1):1-3. doi: 10.1056/NEJMp1813836.

Facing Opioids in the Shadow of the HIV Epidemic.

Author information

1
From the Departments of Sociomedical Sciences (C.M.P., J.S.H.) and Epidemiology (C.B., S.M.), Mailman School of Public Health, Columbia University, and the Department of Psychiatry, School of Medicine, New York University (H.B.H.) - both in New York.
PMID:
30601748
DOI:
10.1056/NEJMp1813836
[Indexed for MEDLINE]
Free full text
Icon for Atypon

Supplemental Content

Support Center