Sabine Kinloch-de Loes

University College London | UCL · Division of Infection and Immunity

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are co...

Persistence of HIV through integration into host DNA in CD4⁺ T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8⁺ T cells are triggered to kill infected CD4⁺ T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has...

Background: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly underst...

Viral load levels in ART-naïve HIV-1 positive individuals. Kruskal-Wallis analysis was performed and significant p-values (p < 0·05) are marked in red.

Association between SLFN11/BST2 and VL in LTNPs. (a) Spearman correlation plots depicting negative correlation for SLFN11 and BST2, with VL. (b) Boxplots showing significantly different SLFN11 and BST2 profile in LTNPs with undetectable versus detectable VL. Statistical Wilcoxon signed rank test was performed and significant p-values (p < 0·05) are...

Background: A wide range of host restriction factors (RF) become upregulated upon HIV-1 infection to suppress viral infectivity and may aid viremic control in vivo. This cross-sectional study evaluated HIV-1 RFs and dependency factors in HIV infected individuals with progressive or non-progressive infection, as well as in early and late treated coh...

BACKGROUND: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing-termed kick and kill regimens-have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to deter...

We are not aware of a report detailing the complex obstetrical and medical management of twin pregnancy in the context of HIV infection and early post-liver transplantation period. Here we describe the successful outcome of a twin pregnancy in a 28-year-old HIV-positive female receiving antiretroviral therapy and immunosuppressive therapy who was t...

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion...

Supporting information. Table A. Summary of log rank test results from Fig D in S1 Text. Table B. Demographic and clinical characteristics of participants in the HEATHER trial included in the analyses. Table C. Correlations of PD-1, Tim-3, Lag-3, PD1/Tim-3, PD1/Lag-3 and Tim-3/Lag-3. Table D. Cox Model adjusted for Tim-3, PD-1, Lag-3, baseline CD4...

Combination antiretroviral therapy during primary human immunodeficiency virus-1 infection may enable long-term drug-free virological control in rare individuals. We describe a female who maintained aviremia and a normal CD4+/CD8+ T cell ratio for 10 years after stopping therapy, despite a persistent viral reservoir. Cellular immune responses may h...

Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of 'post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunolog...

DOI: http://dx.doi.org/10.7554/eLife.09115.008

The aim of this study was to assess cardiovascular diagnoses and management in a cohort of patients diagnosed with HIV, and the performance of a joint HIV/Cardiology Clinic in a tertiary hospital setting. A retrospective analysis was performed on all patients referred to a joint HIV/Cardiology Clinic at our hospital. Data on 120 patients were colle...

Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early...

Background: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify t...

Sample numbers available at each time-point by trial randomization. Numbers of samples available at each time-point are presented. Participants from all three trial arms were included at week 0 as they were all treatment naïve at this point. Not all patients at any one time-point are always represented at other time-points due to variation in sampl...

2 × 2 table comparing the number of patients with different times to 50 and 400 copy/ml rebound and their total and integrated pre-TI HIV-1 DNA levels. Table to compare the association between HIV-1 DNA levels at TI (both Total and Integrated) and time to a plasma viral load of either between 50–400 copies/ml or greater than 400 copies/ml. HIV-1 DN...

Cox regression models for variables associated with time to rebound of 400 copies/ml and sampled at wk48. Table to show results of Cox regression analysis for time to virological rebound of 400 copies/ml of plasma with Total DNA and CD4 T cell count as covariables. Univariable and multivariable data are presented with Hazard Ratios (HR) with 95% Co...

Additional demographics of randomized participants included in untreated and 48 week short-course ART analyses Demographics of participants available for analyses of those randomised to receive either no therapy from PHI (first column) and those randomised to receive 48 of weeks of ART from PHI (second column). Data as indicated were: † determined...

The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis and transformed t...

Background: In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized. Methods: In MONET, patients on stable combination ART...

Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversi...

Gating strategy for identification of CD4+ and CD8+ T-cells. Shown is a representative example of HIV-1 Gag-specific responses from LTTS subject JIM-014 upon 6-hour in vitro stimulation with the Gag peptide pool. This figure illustrates the gating strategy used in the comprehensive analysis of cytokine production and cytotoxic capacity as measured...

Analysis of the magnitude of HIV-1-specific CD8+ T-cell responses. (A) Cumulative data (mean±SE) on the percentage of IFN-γ-, IL-2- and TNF-α-producing HIV-1 specific CD8+ T-cells following 6 hours of in vitro stimulation with ‘favourable’ epitopes (i.e. optimal CD8+ T-cell epitopes known to be associated with good viral control). (B) Cumulative da...

Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-p...

This review focuses on some of the recent advances in the understanding of HIV immunopathogenesis and the diagnosis and treatment of several autoimmune conditions associated with HIV in the era of potent antiretroviral therapy. Chronic immune activation with progressive immune exhaustion are central features of HIV pathogenesis. The role of self-re...

There are strong theoretical arguments for initiating antiretroviral therapy (ART) during primary HIV-1 infection (PHI) to preserve HIV-1-specific T-cell responses and to decrease immune activation. We assessed the degree of immune activation during PHI and after analytical treatment interruption (ATI) in plasma samples from 22 subjects by measurin...

Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of...

The diagnosis of primary HIV-1 infection (PHI) is often missed and requires a high index of suspicion and a thorough knowledge of laboratory methods. We report the case of a young promiscuous male who presented with fever, rash and neurological symptoms 8 weeks after unprotected sexual exposure. Clinical and laboratory investigations showed the pre...

Treatment of primary HIV-1 infection may alter the natural history of HIV-1 infection and delay the need for chronic antiretroviral therapy; it may also be a public health measure. We discuss the results of therapeutic trials and cohort studies, the occurrence of transmitted drug resistance, and recent findings in terms of immunopathogenesis and de...

Blood-based studies have demonstrated the potential of immunological assays to detect tuberculosis. However lung fluid sampling may prove superior as it enables simultaneous microbiological detection of mycobacteria to be performed. Until now this has only been possible using the expensive and invasive technique of broncho-alveolar lavage. We sough...

Enormous progress has been achieved in the management of chronic HIV infection, and this has led to decreased morbidity and mortality. However, it is still unclear when antiretroviral therapy should be started. Although the clinical improvement has been dramatic, the enthusiasm for aggressive and early treatment of HIV infection was soon tempered b...

The success of clinical care for human immunodeficiency virus infection may vary across demographic groups, because of patient- and health care-related factors. A total of 2386 patients sexually infected with the human immunodeficiency virus were seen in a London clinic from July 1, 1999, to December 31, 2004. We examined demographic variation and...

To study innate and adaptive immune responses in gut-associated lymphoid tissue (GALT) as well as peripheral lymphoid tissue (pLT) obtained from individuals with acute HIV-1 infection syndrome. The expression of chemokines [regulated upon activation: normal T cell expressed/secreted (RANTES), macrophage-inflammatory protein (MIP) 1alpha/beta], cyto...

The benefit of transient combination antiretroviral treatment (CART) during acute HIV infection is uncertain. We used the seroconverter database CASCADE to provide a historical comparison for the Quest trial, in which 79 subjects with acute HIV infection received CART for an average of 2.6 years, and 17.7% (95% confidence interval [CI]: 10.9-27.6)...

The antiretroviral therapy efficacy remains unquestioned, though associated with drug resistance, toxicity and high costs. Several strategies of therapeutic immunization are being explored to limit time on treatment and prevent disease progression by increasing the immunological control of HIV. Research on immune correlates of protection suggests t...

Leukemia inhibitor factor (LIF) is thought to play a substantial role in protecting CD4 T cells in lymphoid tissues (LT) from infection by HIV-1. To investigate whether primary HIV-1 infected subjects with sustained virological control (< 1000 HIV-1 RNA copies/ml plasma) post-cessation antiretroviral therapy (ART) had a higher initial LIF response...

Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting HAART who were enrolled in 12 cohorts from Europe a...

Background: Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable.METHODS. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVA...

Highly active antiretroviral therapy (HAART) results in an improvement in immunologic function. We sought to investigate the factors associated with increases in CD4 cell count among human immunodeficiency virus (HIV)-positive antiretroviral-naive patients starting HAART. Five hundred ninety-six subjects were followed for a median of 2.5 years (int...

The recent success of highly active antiretroviral therapy (HAART) has altered the prognosis of patients living with HIV-1 infection. However, there are still many challenges to be addressed if we want to develop long-term therapeutic strategies for patients, in both the Western world and resource-poor countries. In this review, the potential role...

To study the long-term CD4 cell responses to highly active antiretroviral therapy (HAART) in treatment-naive patients whose viral loads remained below 500 copies/ml for prolonged periods. A total of 237 patients whose viral loads remained below 500 copies/ml for one year or more. Median follow-up was 1.9 years. CD4 cell counts were analysed to inve...

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL) responses are detectable shortly after the acute phase of HIV infection, but they cannot control viral replication and prevent development of chronic immune suppression. This article describes a defect in the coexpression of perforin in granzyme A-positive CD8+ T cells in lymp...

In this review, we address recent advances in the understanding of the pathogenesis of human immunodeficiency type 1 virus infection, which have provided the rationale for present trials of therapeutic vaccines. We shall relate this work to lessons of the past few years both in the use of highly active antiretroviral therapy to attempt eradication...

To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART). Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of...

Purpose: By protecting and stimulating HIV-specific CD4 cell responses, treatment of primary HIV infection (PHI) with potent quadruple HAART could lead to prolonged suppression of HIV replication after cessation of antiretroviral therapy. The QUEST trial investigates this hypothesis and aims to determine whether addition of a therapeutic vaccine t...

Background: Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. Objectives: To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a...

Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre...

Objective: To describe the changes over time in incidence of hospital admissions among patients with HIV, reasons for hospital admission, duration of stay, relationship with CD4 T-cell count and with antiretroviral treatment. Methods: The incidence of hospital admissions during each calendar year from 1988 to 1997 inclusive was calculated using a p...

To describe the changes over time in incidence of hospital admissions among patients with HIV, reasons for hospital admission, duration of stay, relationship with CD4 T-cell count and with antiretroviral treatment. The incidence of hospital admissions during each calendar year from 1988 to 1997 inclusive was calculated using a person-years analysis...

Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal tr...

The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta (TCR Vbeta) repertoire dynamics within the peripheral CD4+ T-cell compartment were studied in individuals following HIV seroconversion. Profound TCR Vbeta repertoire perturbations were observed within the CD4+ T-cell pool in treatment-naive patients regardless of their le...

Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. At baseline, additional mutation...

This study examined the relationship between the severity of acute human immunodeficiency virus type 1 (HIV-1) illness and disease progression and death. The population included 218 patients with acute HIV-1 illness and 41 asymptomatic patients who underwent HIV-1 seroconversion; the patients were followed up prospectively. We analyzed progression...

A randomized trial of 77 patients with primary HIV infection concluded that a 6-month course of zidovudine significantly reduced the incidence of opportunistic infections and improved CD4 cell counts. Follow-up was extended over a mean of 28 months to assess whether these benefits persisted beyond the trial period under conditions of routine care....

Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR...

To the Editor —We enjoyed reading Dr Levy's¹ Controversies on surrogate markers in acquired immunodeficiency syndrome research and concur with much of his analysis. However, on a few occasions, he may have carried his argument too far. For instance, we agree that the relationship between low viral load and favorable clinical outcomes seen in studie...

To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell...

Patients with HIV-1 infection are usually not diagnosed until they present with an opportunistic infection, often several years after their initial seroconversion. Increasingly, however, it is recognised that many people suffer an acute mononucleosis-like illness shortly after seroconversion. Despite the protean manifestations of this initial infec...