Publications
478 results found
Tiraboschi J, Ray S, Patel K, et al., 2017, The impact of immunoglobulin in acute HIV infection on the HIV reservoir: a randomized controlled trial., HIV Medicine, ISSN: 1464-2662
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined. RESULTS: IVIG was well tolerated and no viral blips (> 50 HIV-1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: -3.7 log10 copies/10(6) CD4 cells; controls: -3.87 log10 copies/10(6) CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons. CONCLUSIONS: Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue.
Shanaube K, Schaap A, Floyd S, et al., 2017, What works - reaching universal HIV testing: lessons from HPTN 071 (PopART) trial in Zambia, AIDS, Vol: 31, Pages: 1555-1564, ISSN: 0269-9370
Objective: To determine the uptake of home-based HIV counselling and testing (HCT) in four HPTN 071 (PopART) trial communities (implementing a ‘full’ combination HIV prevention package that includes universal HIV testing and treatment) in Zambia. We also explore factors associated with uptake of HCT in these communities.Design: HPTN 071 (PopART) is a three-arm community-randomized trial in 12 communities in Zambia and nine communities in South Africa evaluating the impact of a combination HIV prevention package, including universal HIV testing and treatment, on HIV incidence.Methods: Using a door-to-door approach that includes systematically revisiting households, individuals were offered participation in the intervention, and verbal consent was obtained. Data were analysed for the first 18 months of the intervention, December 2013 to June 2015 for individuals 18 years and older.Results: Among 121 130 enumerated household members, 101 102 (83.5%) accepted the intervention. HCT uptake was 72.2% (66 894/92 612), similar by sex but varied across communities. HCT uptake was associated with younger age, sex, community, being symptomatic for TB and sexually transmitted infections and longer time since previous HIV test. Knowledge of HIV status due to the intervention increased by 36% overall and by 66% among HIV positive participants; the highest impact was among 18–24 years old.Conclusion: Overall acceptance of HIV-testing through offering a door-to-door-based combination HIV prevention package was 72.2%. The intervention increased knowledge of HIV status from ∼50 to ∼90%. However, challenges still remain and a one-off intervention is unlikely to be successful but will require repeated visits and multiple strategies.
White P, Fox J, Weber J, et al., 2017, HOW MUCH CAN HIV TRANSMISSION BE REDUCED IN HIGH-RISK MSM BY TARGETING TESTING TO DETECT AND TREAT PRIMARY HIV INFECTION (PHI)? ANALYSIS OF A COHORT STUDY USING AN INDIVIDUAL-BASED MODEL, P5.23 How much can hiv transmission be reduced in high-risk msm by targeting testing to detect and treat primary hiv infection (PHI)? analysis of a cohort study using an individual-based model, Publisher: BMJ PUBLISHING GROUP, Pages: A243-A244, ISSN: 1368-4973
Shanaube K, Schaap A, Chaila MJ, et al., 2017, Community intervention improves knowledge of HIV status of adolescents in Zambia: findings from HPTN 071-PopART for youth study, AIDS, Vol: 31, Pages: S221-S232, ISSN: 0269-9370
Objective: To determine the uptake of home-based HIV counselling and testing (HCT) in four communities of the HPTN 071 (PopART) trial in Zambia among adolescents aged 15–19 years and explore factors associated with HCT uptake.Design: The PopART for youth study is a three-arm community-randomized trial in 12 communities in Zambia and nine communities in South Africa which aims to evaluate the acceptability and uptake of a HIV prevention package, including universal HIV testing and treatment, among young people. The study is nested within the HPTN 071 (PopART) trial.Methods: Using a door-to-door approach that includes systematically revisiting households, all adolescents enumerated were offered participation in the intervention and verbal consent was obtained. Data were analysed from October 2015 to September 2016.Results: Among 15 456 enumerated adolescents, 11 175 (72.3%) accepted the intervention. HCT uptake was 80.6% (8707/10 809) and was similar by sex. Adolescents that knew their HIV-positive status increased almost three-fold, from 75 to 210. Following visits from community HIV care providers, knowledge of HIV status increased from 27.6% (3007/10 884) to 88.5% (9636/10 884). HCT uptake was associated with community, age, duration since previous HIV test; other household members accepting HCT, having an HIV-positive household member, circumcision, and being symptomatic for STIs.Conclusion: Through a home-based approach of offering a combination HIV prevention package, the proportion of adolescents who knew their HIV status increased from ∼28 to 89% among those that accepted the intervention. Delivering a community-level door-to-door combination, HIV prevention package is acceptable to many adolescents and can be effective if done in combination with targeted testing.
Martin GE, Pace M, Thornhill JP, et al., 2017, Enrichment of the HIV reservoir in CD32+CD4 T cells occurs early and is closely associated with immune checkpoint receptor expression, Publisher: JOHN WILEY & SONS LTD, Pages: 103-103
Ayles H, Floyd S, Mulubwa C, et al., 2017, Increasing knowledge of HIV status among men: a cluster-randomized trial of community-based distribution of oral HIV self-test kits nested in four HPTN 071 communities in Zambia, Publisher: JOHN WILEY & SONS LTD, Pages: 112-113
Rutstein SE, Ananworanich J, Fidler S, et al., 2017, Clinical and public health implications of acute and early HIV detection and treatment: a scoping review, Journal of the International AIDS Society, Vol: 20, ISSN: 1758-2652
Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years.Results and Discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI – evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting.Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and lo
Palmer DS, Turner I, Fidler S, et al., 2017, Mapping the drivers of within-host pathogen evolution using massive data sets
<jats:title>Abstract</jats:title><jats:p>Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Identifying such interactions can potentially be achieved through genetic association studies. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. To address these problems, we have developed a Bayesian approach for detecting host influences on pathogen evolution that makes use of vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Using simulations and empirical analysis of drug-induced selection on the HIV-1 genome we demonstrate the power of the method to recover known associations and show greatly improved precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.</jats:p>
Kratochvil S, McKay PF, Kopycinski JT, et al., 2017, A phase 1 human immunodeficiency virus vaccine Trial for cross-profiling the kinetics of serum and mucosal antibody responses to CN54gp140 modulated by two homologous prime-boost vaccine regimens, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224
A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months. The two homologous prime-boost regimens were well tolerated and induced CN54gp140-specific responses that were observed in both the systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with FcγR engagement, and both vaccine regimens were associated with strikingly similar patterns in antibody titer and FcγR-binding profiles. In both groups, identical changes in the antigen (Ag)-specific IgG-subclass fingerprint, leading to a decrease in IgG1 and an increase in IgG4 levels, were modulated by booster injections. Here, the dissection of immune profiles further supports the notion that prime-boost strategies are essential for the induction of diverse Ag-specific HIV-1 responses. The results reported here clearly demonstrate that identical responses were effectively and safely induced by both vaccine regimens, indicating that an accelerated 6-month regimen could be employed for the rapid induction of immune responses against CN54gp140 with no apparent impact on the overall quality of the induced immune response. (This study has been registered at http://ClinicalTrials.gov under registration no. NCT01966900.)
Lam PK, Fidler S, Foster C, 2017, A review of transition experiences in perinatally and behaviourally acquired HIV-1 infection; same, same but different?, Journal of the International AIDS Society, Vol: 20, ISSN: 1758-2652
Introduction: Despite sharing common psychosocial and developmental experiences, adolescents living with perinatally and behaviourally acquired HIV-1 infection are different in terms of timing of HIV infection and developmental stage at infection. Therefore, it is of interest to identify similarities and differences between these two groups of adolescents living with HIV in their experiences, facilitators and barriers during the transition process.Methods: A detailed literature search of peer-reviewed published papers was conducted on PubMed to identify relevant original research or viewpoints published up to September 2016. Conference abstracts and other unpublished data sources were not included.Results: Existing published literature, mainly using qualitative methods, explores the transition from paediatric to adult healthcare provision, as experienced by these two groups of young people. Reports highlight the variation and similarities in their experiences and challenges of transition. Findings from the USA and Europe predominate, while experience from Africa and Asia is lacking, despite the importance of these regions in the global epidemic.Conclusions: Published transition data remain limited, and there are few studies focusing on behaviourally infected adolescents and key population groups (e.g. adolescents who use drugs, lesbian/gay/transgender individuals). Robust definitions of the transition process and standardized outcome measures are required to facilitate cross-study and geographic comparisons.
Hayes R, Floyd S, Schaap A, et al., 2017, A universal testing and treatment intervention to improve HIV control: One-year results from intervention communities in Zambia in the HPTN 071 (PopART) cluster-randomised trial, PLoS Medicine, Vol: 14, ISSN: 1549-1277
Background:The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention.Methods and findings:The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121,130 adults (59,283 men and 61,847 women) were enumerated in 46,714 households during the first annual round (December 2013 to June 2015). Of the 45,399 (77%) men and 55,703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6,197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%–43%) initiated ART within 6 mo and 53% (95% CI: 52%–55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to
Winston A, Julie F, Fidler S, 2017, HIV cure strategies: response to ignore the central nervous system at your patients' peril, AIDS, Vol: 31, Pages: 1051-1052, ISSN: 0269-9370
Chereau F, Madec Y, Sabina C, et al., 2017, Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers, PLOS ONE, Vol: 12, ISSN: 1932-6203
Objective:HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control.Methods:HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models.Results:We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds.Discussion:Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs.
Venturelli S, McKenna W, Carder M, et al., 2017, START: how long does it take to start antiretroviral therapy (ART)?, Publisher: WILEY, Pages: 20-20, ISSN: 1464-2662
Thornhill J, Herrera C, Olejniczak N, et al., 2017, Impact of ART in primary HIV infection on T cell immune exhaustion in gut-associated lymphoid tissue: implications for HIV persistence, Publisher: WILEY, Pages: 6-6, ISSN: 1464-2662
Wallace Z, Yang H, Chojnacki J, et al., 2017, Engineered affinity-enhanced immune-mobilising monoclonal T cell receptors (ImmTAVs) for HIV cure, Publisher: WILEY, Pages: 7-7, ISSN: 1464-2662
Fyles F, Foster C, Fidler S, 2017, Bone density measurements amongst young adults with perinatally acquired HIV infection in routine care, Publisher: WILEY, Pages: 35-35, ISSN: 1464-2662
Zijlstra G, Fidler S, Limbada M, et al., 2017, A literature review of the effectiveness of programmes delivering antiretroviral therapy in non-facility based settings in sub-Saharan Africa, Publisher: WILEY, Pages: 59-60, ISSN: 1464-2662
Thornhill J, Fidler S, Martin G, et al., 2017, Diagnosis of primary HIV infection with rapid ART in the HEATHER cohort: towards zero infections, Publisher: WILEY, Pages: 23-24, ISSN: 1464-2662
Martin GE, Gossez M, Williams JP, et al., 2017, Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection, AIDS, Vol: 31, Pages: 477-484, ISSN: 0269-9370
Objective(s): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption.Design: Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial.Methods: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for >=16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8+ responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry.Results: At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4+ : CD8+ ratios (all P < 0.001) and higher CD4+ cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect.Conclusion: Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies.
Fidler S, Olson AD, Bucher HC, et al., 2017, Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection., Journal of Acquired Immune Deficiency Syndromes, Vol: 74, Pages: 126-133
Background: Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research.Methods: Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by <400 copies HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders.Results: Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0–35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA <50 copies per milliliter ≥24 months after ART cessation.Conclusion: HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.
Thornhill JP, Fidler S, Klenerman P, et al., 2017, The role of CD4+T follicular helper cells in HIV infection: from the germinal center to the periphery, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224
T follicular helper cells (TFh) are key components of the adaptive immune system; they are primarily found in germinal centers (GCs) where their interaction with B cells supports humoral immune responses and efficient antibody production. They are defined by the expression of CXC receptor 5, program death-1, ICOS, and secretion of IL-21. Their differentiation is regulated by B-cell lymphoma 6. The relationship and function of circulating TFh to bona fide TFh resident in the GC is much debated. HIV infection impacts the TFh response with evidence of aberrant TFh function observed in acute and chronic infection. Effective TFh responses are associated with the development of broadly neutralizing antibody responses to HIV and may be important for viral control. In addition, TFh are preferentially infected and act as a key reservoir for latent HIV infection. This review explores recent developments in our understanding of TFh differentiation, regulation, function, and the relationship between cTFh and those in GCs, and the complex interaction between TFh and HIV infection.
Kim S, Kim SH, McDonald S, et al., 2017, Transition to adult services - a positive step, AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV, Vol: 29, Pages: 885-889, ISSN: 0954-0121
Yebra G, Hodcroft EB, Ragonnet-Cronin ML, et al., 2016, Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic., Scientific Reports, Vol: 6, ISSN: 2045-2322
HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case. We built maximum-likelihood trees for each combination using RAxML (GTR + Γ), and compared their topologies to the corresponding true tree's using CompareTree. The accuracy of the trees was significantly proportional to the length of the sequences used, with the gag-pol-env datasets showing the best performance and gag and partial pol sequences showing the worst. The lowest sampling depths (20% and 5%) greatly reduced the accuracy of tree reconstruction and showed high variability among replicates, especially when using the shortest gene datasets. In conclusion, using longer sequences derived from nearly whole genomes will improve the reliability of phylogenetic reconstruction. With low sample coverage, results can be highly variable, particularly when based on short sequences.
Bock P, James A, Nikuze A, et al., 2016, Baseline CD4 Count and Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 73, Pages: 514-521, ISSN: 1525-4135
Tiraboschi J, Ray S, Patel K, et al., 2016, Short Communication: Lack of Effect of Maraviroc Intensification on Blood and Gut Reservoir, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 33, Pages: 143-146, ISSN: 0889-2229
Bergin P, Langat R, Omosa-Manyonyi G, et al., 2016, Assessment of anti-HIV-1 antibodies in oral and nasal compartments of volunteers from three different populations, JAIDS - Journal of Acquired Immune Deficiency Syndromes, Vol: 73, Pages: 130-137, ISSN: 1525-4135
In this study, we assessed the feasibility of collecting standardized nasal and salivary samples at centers in Nairobi (Kenya), Kigali (Rwanda) and London (UK) using different collection devices and media (Synthetic absorptive matrices versus flocked swabs, and Salimetrics Oral swabs versus whole oral fluid collection). We detected anti Gag (p24) and envelope (gp140) antibodies in both nasal fluid and salivary collections from all HIV-infected individuals, and cross-reactive anti-p24 antibodies were detected in 10% of HIV-uninfected individuals enrolled at one site. Collections from the nasal turbinates were comparable to samples collected deeper in the nasopharyngeal tract, and the yield of anti-p24 IgA in the whole oral fluid samples was higher than in samples collected from the parotid gland. We noted a trend toward reduced levels of anti-HIV antibody in the volunteers receiving anti-retroviral therapy (ART). Levels of antibodies were stable over multiple collection visits. Overall, this study shows that nasal and salivary samples can be collected in a standardized manner over repeated visits in both low and high resource settings. These methods may be used in support of future HIV vaccine clinical trials.
Churchill D, Waters L, Ahmed N, et al., 2016, British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015, HIV Medicine, Vol: 17, Pages: s2-s104, ISSN: 1464-2662
Pace M, Williams J, Kurioka A, et al., 2016, Histone Deacetylase Inhibitors Enhance CD4 T Cell Susceptibility to NK Cell Killing but Reduce NK Cell Function, PLOS Pathogens, Vol: 12, ISSN: 1553-7366
In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells. HDACi-treated HIV-1-infected CD4 T cells were also more effectively cleared than untreated controls during NK co-culture. However, HDACi impaired NK function, reducing degranulation and killing capacity. Depending on the HDACi and dose, this impairment could counteract the benefit gained by treating infected target cells. These data suggest that following HDACi-induced HLA class I down-regulation NK cells kill HIV-1-infected cells, although HDACi-mediated NK cell inhibition may negate this effect. Our data emphasize the importance of studying the effects of potential interventions on both targets and effectors.
Bond V, Chiti B, Hoddinott G, et al., 2016, "The difference that makes a difference": highlighting the role of variable contexts within an HIV Prevention Community Randomised Trial (HPTN 071/PopART) in 21 study communities in Zambia and South Africa., AIDS Care, Vol: 28, Pages: 99-107, ISSN: 0954-0121
This paper explores contextual heterogeneity within a community randomised trial HPTN 071 (Population Effects of Antiretroviral Treatment to Reduce HIV Transmission) carried out in 21 study communities (12 Zambian, 9 South African). The trial evaluates the impact of a combination HIV prevention package (including household-based HIV counselling and testing and anti-retroviral treatment (ART) eligibility regardless of CD4-count) on HIV incidence. The selection, matching and randomisation of study communities relied on key epidemiological and demographic variables and community and stakeholder support. In 2013, following the selection of study communities, a "Broad Brush Survey" (BBS) approach was used to rapidly gather qualitative data on each study community, prior to the implementation of the trial intervention. First-year process indicator intervention data (2014-2015) were collected during the household-based intervention by community lay workers. Using an open/closed typology of urban communities (indicating more or less heterogeneity), this qualitative inquiry presents key features of 12 Zambian communities using a list of four meta-indicators (physical features, social organisation, networks and community narratives). These indicators are then compared with four intervention process indicators in a smaller set of four study communities. The process indicators selected for this analysis indicate response to the intervention (uptake) amongst adults. The BBS qualitative data are used to interpret patterns of similarity and variability in the process indicators across four communities. We found that meta-indicators of local context helped to interpret patterns of similarity and variability emerging across and within the four communities. Features especially significant for influencing heterogeneity in process indicators include proportion of middle-class residents, proximity to neighbouring communities and town centre, the scale of the informal economy
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