Publications
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Alagaratnam J, Stohr W, Toombes J, et al., 2019, No evidence of neuroaxonal injury following latency reversal with vorinostat and HIV-1 specific vaccination in the RIVER trial, Publisher: WILEY, Pages: 25-25, ISSN: 1464-2662
Foster C, Rees C, Ayers S, et al., 2019, The impact of weather and college holidays on attendance at HIV youth services, Publisher: WILEY, Pages: 73-73, ISSN: 1464-2662
Mallik I, Fidler S, Foster C, 2019, An evaluation of quality of life through educational, vocational and housing outcomes for adults living with perinatally acquired HIV, Publisher: WILEY, Pages: 60-60, ISSN: 1464-2662
Pasvol T, Teh J, Balfoussia D, et al., 2019, Feasibility, acceptability and outcomes of fertility evaluation in adults with perinatally acquired HIV-1 infection: a cross-sectional observational study, Publisher: WILEY, Pages: 74-75, ISSN: 1464-2662
Cole M, Saeed Z, Shaw AT, et al., 2019, Equivalent responses to quadrivalent influenza vaccine are detectable in blood and oral fluid in healthcare workers and men living with HIV on ART, Publisher: WILEY, Pages: 10-10, ISSN: 1464-2662
Cole M, Saeed Z, Shaw AT, et al., 2019, Responses to quadrivalent influenza vaccine reveal the landscape of CD32 expression on circulating T-follicular helper cells in men living with HIV infection, Publisher: WILEY, Pages: 25-25, ISSN: 1464-2662
Kanfer E, Bower M, Fidler S, et al., 2019, First report of maternal donor in haemopoietic stem cell transplantation for lymphoma associated with perinatal HIV, Publisher: WILEY, Pages: 32-32, ISSN: 1464-2662
Ratmann O, Grabowski MK, Hall M, et al., 2019, Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis, Nature Communications, Vol: 10, ISSN: 2041-1723
To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8–28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.
Martin GE, Pace M, Shearer F, et al., 2019, HIV reservoir size is determined prior to ART initiation and linked to CD8 T cell activation and memory expansion
<jats:title>Abstract</jats:title><jats:p>Initiation of antiretroviral therapy (ART) in early compared with chronic HIV infection is associated with a smaller HIV reservoir. This longitudinal analysis of 63 individuals who commenced ART during primary HIV infection (PHI) investigates which pre-and post-therapy factors associate most closely with reservoir size (HIV DNA) following treatment initiation during PHI. The best predictor of reservoir size at one-year was pre-ART HIV DNA which was in turn significantly associated with CD8 memory differentiation (effector memory, naïve and T-bet<jats:sup>neg</jats:sup>Eomes<jats:sup>neg</jats:sup>subsets), CD8 T cell activation (CD38 expression) and PD-1 and Tim-3 expression on memory CD4 T cells. No associations were found for any immunological variables following one-year of ART. HIV reservoir size is determined around the time of ART initiation in individuals treated during PHI. CD8 T cell activation and memory expansion are linked to HIV reservoir size, suggesting the importance of the initial host-viral interplay in eventual reservoir size.</jats:p>
Mulubwa C, Hensen B, Phiri MM, et al., 2019, Community based distribution of oral HIV self-testing kits in Zambia: a cluster-randomised trial nested in four HPTN 071 (PopART) intervention communities, Lancet HIV, Vol: 6, Pages: E81-E92, ISSN: 2405-4704
BackgroundThe HPTN 071 (PopART) cluster-randomised trial provided door-to-door HIV testing services to a large proportion of individuals residing in 21 intervention communities in Zambia and South Africa from 2014 to 2017 and reached the UNAIDS first 90 target among women in Zambia, yet gaps remained among men and young adults. This cluster-randomised study nested in the HPTN 071 (PopART) trial sought to increase knowledge of HIV status across all groups by offering the choice of oral HIV self-testing in addition to routine door-to-door HIV testing services.MethodsWe nested this cluster-randomised trial in four HTPN 071 (PopART) intervention communities in northern Zambia. 66 zones (clusters) in these communities were randomly allocated (1:1) to either oral HIV self-testing plus routine door-to-door HIV testing services (HIV self-testing group) or the PopART standard of care of door-to-door HIV testing services alone (non- HIV self-testing group) over a 3-month period. All individuals aged 16 years or older were eligible for HIV testing. Randomisation was achieved by randomly selecting one allocation from a list of 10 000 possible allocations during a public ceremony. In HIV self-testing zones, trained lay-counsellors (known as community HIV care providers) visited households and offered eligible individuals the choice of HIV testing using HIV self-testing or routine door-to-door HIV testing services. For individuals aged 18 years or older whose partner was absent during the household visit, an HIV self-test kit could be left for secondary distribution to the absent partner. The primary outcome was knowledge of HIV status (defined as self-reporting HIV positive to the community HIV care providers or accepting an offer of HIV testing services). Outcomes were measured among households that were first visited, and individuals first enumerated as a household member during the HIV self-testing intervention period. We analysed data at the individual level using population
Gossez M, Martin GE, Pace M, et al., 2019, Virological remission after antiretroviral therapy interruption in female African HIV seroconverters, AIDS, Vol: 33, Pages: 185-197, ISSN: 0269-9370
INTRODUCTION: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). METHODS: We studied participants (n = 82) from South Africa and Uganda in Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion, the first trial of treatment interruption in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4 T cells, CD4 cell count, plasma viral load (pVL), cell-associated HIV RNA and T-cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after treatment interruption (n = 22). Data were compared with non-African Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion participants. RESULTS: Pretherapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs. 4.72 log10 copies/ml and 3.07 vs. 3.61 log10 copies/million CD4 T cells, respectively; P < 0.001). Pre-ART HIV DNA in Africans was associated with clinical progression (P = 0.001, HR per log10 copies/million CD4 T cells increase (95% CI) 5.38 (1.95-14.79)) and time to pVL rebound (P = 0.034, HR per log10 copies/ml increase 4.33 (1.12-16.84)). After treatment interruption, Africans experienced longer duration of viral remission than non-Africans (P < 0.001; HR 3.90 (1.75-8.71). Five of 22 African participants (22.7%) maintained VL less than 400 copies/ml over a median of 188 weeks following treatment interruption. CONCLUSION: We find evidence of greater probability of virological remission following treatment interruption among African participants, although we are unable to differentiate between sex, ethnicity and viral subtype. The finding warrants further investigation.
Lee MJ, Venturelli S, McKenna W, et al., 2019, Reasons for delayed antiretroviral therapy (ART) initiation in the era of early ART initiation guidelines: a retrospective service evaluation., Int J STD AIDS, Pages: 956462418814985-956462418814985
Following changes in national antiretroviral therapy (ART) guidelines removing the CD4 threshold for initiation of ART, we evaluated the time to ART initiation and reasons for delayed or non-initiation. A retrospective notes review of 292 newly diagnosed HIV-positive individuals attending two London clinics between August 2015 and December 2016 was performed. Two hundred and fifty-four of 292 (87%) individuals started ART. Median time to ART initiation was 29 days (range: 0-514). Thirty of 292 (13%) did not start ART. Rates of virological suppression at six months were similar regardless of time to ART initiation. People who inject drugs (16.7% vs. 3.6%) (p = 0.009), having a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p = 0.001), and having gastrointestinal/liver co-morbidities (23% vs. 9%, p = 0.001) were associated with delayed ART initiation. The cohort not on ART had a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p < 0.001). Documented reasons for delayed or ART non-initiation included patient's choice, prolonged adjustment periods, and difficulty leaving work. We conclude that delayed or non-initiation of ART was associated with injecting drug use and prolonged adjustment to a new HIV diagnosis. Clinician factors may include lack of urgency with higher baseline CD4 cell counts. Improved linkage to care and drug services pathways may encourage timely ART initiation.
Teh J, Pasvol T, Ayres S, et al., 2019, Case series of infertility amongst young women with perinatally acquired HIV: data from a London cohort, Journal of virus eradication, Vol: 5, Pages: 44-46, ISSN: 2055-6640
Introduction: Increased rates of infertility have been reported in women who acquired HIV horizontally compared to population age-matched normative data. However, few data exist for adults with perinatally acquired HIV (PaHIV), who have been exposed to antiretroviral drugs and/or HIV-associated ill health through childhood and puberty. We describe a case series of infertility amongst women with PaHIV attending a London clinic between 2006 and 2017. Methods: A retrospective case-note review was conducted amongst all female PaHIV patients aged >16 years attending a London clinic. All data was captured into an electronic database using paper and electronic clinical records taken from every routine clinic visit (average three times/year between 2006 and 2017). Data captured included HIV viral load, CD4 cell count, antiretroviral therapy regimen, sexual and reproductive health and STI screening. Age-matched analysis of infertility rates compared to the general population were not performed. Results: In total, 119 young women were included, with a median age of 20 years (interquartile range [IQR] 18-24, range 16-33 years) at latest follow-up. Three women with PaHIV were diagnosed with infertility (n=3): two with primary ovarian insufficiency (n=2) and one with hypogonadotropic hypogonadism (n=1). A further 5/116 (4.3%) were under investigation for menstrual irregularities. Of the remaining 111 young women, 17 (15%) had successfully conceived. All patients were currently prescribed ART, with 93 (78%) having an HIV VL <50 copies/mL at their last visit. Median ART exposure was 13 (IQR 9-17) years. Among five women with reported irregular menstrual cycles there was no correlation with current CD4 cell count, HIV VL or length of ART exposure, although there was an increased prevalence of body mass index >25 kg/m(2) (63% vs 30%). Conclusion: Overall the reproductive health status for young women with PaHIV was comparable to the general population.
Teh J, Pasvol T, Ayres S, et al., 2019, Case series of infertility amongst young women with perinatally acquired hiv: Data from a london cohort, HIV Nursing, Vol: 19, Pages: 17-19, ISSN: 1474-7359
Introduction: Increased rates of infertility have been reported in women who acquired HIV horizontally compared to population age-matched normative data. However, few data exist for adults with perinatally acquired HIV (PaHIV), who have been exposed to antiretroviral drugs and/or HIV-associated ill health through childhood and puberty. Methods: A retrospective case-note review was conducted amongst all female PaHIV patients aged >16 years attending a London clinic. Results: In total, 119 young women were included, with a median age of 20 years. Three women with PaHIV were diagnosed with infertility: two with primary ovarian insufficiency and one with hypogonadotropic hypogonadism. A further five were under investigation for menstrual irregularities. Of the remaining 111 young women, 17 had successfully conceived. Conclusion: Overall the reproductive health status for young women with PaHIV was comparable to the general population.
Psomas CK, Fidler S, Macartney M, et al., 2018, Highlights from the 22nd International AIDS Conference (AIDS 2018), 22-27 July 2018, Amsterdam , the Netherlands, Journal of virus eradication, Vol: 4, Pages: 238-247, ISSN: 2055-6640
Important data on the social, epidemiological and clinical aspects of HIV-1, comorbidities and hepatitis as well as data on novel antiretroviral agents and the cure agenda were presented at AIDS 2018. this report covers some of the highlights.
Seers T, Vassallo P, Pollock KM, et al., 2018, CD4/CD8 ratio in children with perinatally acquired HIV-1 infection, HIV Medicine, Vol: 19, Pages: 668-672, ISSN: 1464-2662
BackgroundIn adults with horizontally acquired HIV an inverted CD4/CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non-AIDS adverse events. Normalisation of this ratio with antiretroviral therapy (ART) is sub-optimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4/CD8 ratio recovery in children with perinatally-acquired HIV (PaHIV) on ART.MethodsCross-sectional, retrospective analysis of routine clinical data in children with PaHIV (5-18yrs) attending a single UK centre. ResultsCD4/CD8 normalisation was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4/CD8 ratio and age at start of ART. Positive correlations were found between current CD4/CD8 ratio and total time with suppressed HIV viral load, and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4/CD8 ratio (standardised β -0.680, p<0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery.ConclusionsWe found higher rates of CD4/CD8 ratio normalisation compared to previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV-positive adults and children will enhance immunological normalisation.
Fidler S, 2018, Approaches towards a cure for HIV, Publisher: JOHN WILEY & SONS LTD
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Floyd S, Ayles H, Schaap A, et al., 2018, Towards 90-90: Findings after two years of the HPTN 071 (PopART) cluster-randomized trial of a universal testing-and-treatment intervention in Zambia, PLOS ONE, Vol: 13, ISSN: 1932-6203
BackgroundHPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the “PopART” universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage.Methods and findingsThe second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used “time-to-event” methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs’ electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+
Bradley J, Floyd S, Piwowar-Manning E, et al., 2018, Sexually transmitted bedfellows: exquisite association between HIV and HSV2 in 21 communities in Southern Africa in the HPTN 071 (PopART) study, Journal of Infectious Diseases, Vol: 218, Pages: 443-452, ISSN: 0022-1899
Background: HIV and Herpes simplex virus type-2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed re-examination of this association at individual and community levels. Methods: HPTN 071 (PopART) evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV incidence, a cohort of ~2,000 adults (18-44y) was selected randomly from each community. Baseline data on socio-demographic characteristics, behaviour and HIV/HSV2 serology were used to examine the association between HIV and HSV2. At community-level, HIV prevalence was plotted against HSV2 prevalence. Results: 38,691 adults participated. HSV2 prevalence in women/men was 50%/22% (Zambia) and 60%/27% (South Africa). Estimated HSV2 incidence in those aged 18-24y was 8.06 (95%:CI:6.76-9.35) and 1.76 (95%CI:1.30-2.22) per 100/py in women and men, respectively. Six-fold higher odds of HIV were seen in HSV2-infected individuals in both sexes, after adjustment for confounders (Women:OR:6.66,95%CI: 6.07-7.31;Men:OR:6.57,95%CI:5.56-7.77). At community-level there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92,p<0.001). Conclusions: There was an exquisite association between these two infections, at individual and community levels, likely due partly to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.
Sabapathy K, Hensen B, Varsaneux O, et al., 2018, The cascade of care following community-based detection of HIV in sub-Saharan Africa - A systematic review with 90-90-90 targets in sight, PLoS ONE, Vol: 13, ISSN: 1932-6203
Introduction:We aimed to establish how effective community-based HIV testing services (HTS), including home and community location based (non-health facility) HIV testing services (HB-/CLB-HTS), are in improving care in sub-Saharan Africa (SSA), with a view to achieving the 90-90-90 targets.Methods:We conducted a systematic review of published literature from 2007–17 which reported on the proportion of individuals who link-to-care and/or initiate ART after detection with HIV through community-based testing. A meta-analysis was deemed inappropriate due to heterogeneity in reporting.Results and discussion:Twenty-five care cascades from 6 SSA countries were examined in the final review– 15 HB-HTS, 8 CLB-HTS, 2 combined HB-/CLB-HTS. Proportions linked-to-care over 1–12 months ranged from 14–96% for HB-HTS and 10–79% for CLB-HTS, with most studies reporting outcomes over short periods (3 months). Fewer studies reported ART-related outcomes following community-based testing and most of these studies included <50 HIV-positive individuals. Proportions initiating ART ranged from 23–93%. One study reported retention on ART (76% 6 months after initiation). Viral suppression 3–12 months following ART initiation was 77–85% in three studies which reported this.There was variability in definitions of outcomes, numerators/denominators and observation periods. Outcomes varied between studies even for similar time-points since HTS. The methodological inconsistencies hamper comparisons. Previously diagnosed individuals appear more likely to link-to-care than those who reported being newly-diagnosed. It appears that individuals diagnosed in the community need time before they are ready to link-to-care/initiate ART. Point-of-care (POC) CD4-counts at the time of HTS did not achieve higher proportions linking-to-care or initiating ART. Similarly, follow-up visits to HIV-positive individuals did not appear to enhance linkage to care overal
Bond V, Ngwenya F, Thomas A, et al., 2018, Spinning plates: livelihood mobility, household responsibility and anti-retroviral treatment in an urban Zambian community during the HPTN 071 (PopART) study, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652
INTRODUCTION: Qualitative data are lacking on the impact of mobility among people living with HIV (PLHIV) and their decision-making around anti-retroviral treatment (ART). We describe challenges of juggling household responsibility, livelihood mobility and HIV management for six PLHIV in urban Zambia. METHODS: Six PLHIV (three men and three women, aged 21 to 44) were recruited from different geographic zones in one urban community drawn from a qualitative cohort in a social science component of a cluster-randomized trial (HPTN071 PopART). Participants were on ART (n = 2), not on ART (n = 2) and had started and stopped ART (n = 2). At least two in-depth interviews and participant observations, and three drop-in household visits with each were carried out between February and August 2017. Themed and comparative analysis was conducted. RESULTS: The six participants relied on the informal economy to meet basic household needs. Routine livelihood mobility, either within the community and to a nearby town centre, or further afield for longer periods of time, was essential to get by. Although aware of ART benefits, only one of the six participants managed to successfully access and sustain treatment. The other five struggled to find time to access ART alongside other priorities, routine mobility and when daily routines were more chaotic. Difficulty in accessing ART was exacerbated by local health facility factors (congestion, a culture of reprimanding PLHIV who miss appointments, sporadic rationed drug supply), stigma and more limited social capital. CONCLUSIONS: Using a time-space framework illustrated how household responsibility, livelihood mobility and HIV management every day were like spinning plates, each liable to topple and demanding constant attention. If universal lifelong ART is to be delivered, the current service model needs to adjust the limited time that some PLHIV have to access ART because of household responsibilities and th
Mancini E, Quax R, De Luca A, et al., 2018, A study on the dynamics of temporary HIV treatment to assess the controversial outcomes of clinical trials: An<i> in-silico</i> approach, PLOS ONE, Vol: 13, ISSN: 1932-6203
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Foster C, Fidler S, Lyall E, et al., 2018, Careful consideration when responding to new data: dolutegravir and pregnancy, Journal of virus eradication, Vol: 4, Pages: 208-208, ISSN: 2055-6640
This case highlights the current complexities of managing women in the early stages of pregnancy presenting on dolutegravir-based regimens. When responding to new data, there is an important decision to be made, between the potential, uncertain risk of teratogenicity against the potential increased risk of in utero vertical transmission of HIV-1.
Chhabra S, Fidler S, Bower M, et al., 2018, Malignancy and all-cause mortality: incidence in teenage young adults living with perinatally acquired HIV, Publisher: JOHN WILEY & SONS LTD, Pages: 62-63
Thornhill JP, Martin GE, Hoare J, et al., 2018, Follicular CD8+T-cells in gut-associated lymphoid tissue are associated with lower HIV-1 reservoir in the terminal ileum after ART initiated during primary HIV infection, Publisher: JOHN WILEY & SONS LTD, Pages: 96-96
Fidler S, Stohr W, Pace M, et al., 2018, A randomised controlled trial comparing the impact of antiretroviral therapy (ART) with a "Kick-and-Kill" approach to ART alone on HIV reservoirs in individuals with primary HIV infection (PHI); RIVER trial, Publisher: JOHN WILEY & SONS LTD, Pages: 155-155
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Floyd S, Shanaube K, Schaap A, et al., 2018, Linkage to HIV care following HIV self-testing: a cluster randomised 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: 140-141
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Bonsall D, Golubchik T, Kosloff B, et al., 2018, HIV genotyping and phylogenetics in the HPTN 071 (PopART) study: validation of a high-throughput sequencing assay for viral load quantification, genotyping, resistance testing and high-resolution transmission networking, Publisher: JOHN WILEY & SONS LTD, Pages: 58-59
Martin GE, Pace M, Thornhill JP, et al., 2018, CD32-Expressing CD4 T Cells are phenotypically diverse and can contain proviral HIV DNA, Frontiers in Immunology, Vol: 9, ISSN: 1664-3224
Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low, CD32+CD14+, and CD32high). Of note, CD4 negative enrichment kits remove the majority of CD4+CD32+ T cells, potentially skewing subsequent analyses if used. CD32high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3+CD4+CD32+ phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32+ T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.
Pasvol TJ, Foster C, Fidler S, 2018, Novel therapies/hopes for HIV cure in perinatally acquired HIV-positive adolescents., Current Opinion in HIV and AIDS, Vol: 13, Pages: 281-287, ISSN: 1746-630X
PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution. RECENT FINDINGS: In the past year, there have been additional case reports of post-treatment viral control amongst perinatally acquired HIV adolescents and young adults (PaHIV-AYA). In this article, we review and compare the characteristics of PTC in PaHIV-AYA and discuss the potential implications of these observations for the growing population of adolescents living with HIV. The correlation between low levels of HIV DNA and seroreversion may provide a feasible screening tool to select candidates most suitable for future intervention studies and viral remission. CONCLUSION: Whilst it is premature to anticipate an HIV cure, there is much anticipation that with early ART and additional interventions to perturb the residual viral reservoir, future viral remission off ART might be feasible for PaHIV-AYA. However, given the safety and effectiveness of current ART, a critical debate must evaluate the risks against benefits of any novel intervention, especially amongst adolescents as they become sexually active.
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