ABSTRACT
BACKGROUND: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV). METHODS: Young people with PHIV in the United Kingdom, followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onward were included. Changes in CD4 count over time from age 10 to 20 years were analyzed using mixed-effects models, and were compared to published CD4 data for the gerneral population. Potential predictors were examined and included demographics, age at ART start, nadir CD4 z score (age-adjusted) in childhood, and time-updated viral load. RESULTS: Of 1258 young people with PHIV included, 669 (53%) were female, median age at ART initiation was 8.3 years, and the median nadir CD4 z score was -4.0. Mean CD4 count was higher in young people with PHIV who started ART before age 10 years and had a nadir CD4 z score ≥-4; these young people with PHIV had a decline in CD4 count after age 10 that was comparable to that of the general population. Mean CD4 count was lower in young people with PHIV who had started ART before age 10 and had a nadir CD4 z score <-4; for this group, the decline in CD4 count after age 10 was steeper over time. CONCLUSIONS: In children, in addition to starting ART at an early age, optimizing ART to maintain a higher CD4 z score during childhood may be important to maximizing immune reconstitution later in life.
Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Child , Female , Humans , Male , Young Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes , HIV , HIV Infections/drug therapy , HIV Infections/epidemiology , Viral LoadABSTRACT
PURPOSE OF REVIEW: HIV screening in pregnancy, universal suppressive antiretroviral therapy (ART) and breastfeeding avoidance can almost completely prevent vertical transmission of HIV. Breastfeeding is associated with an additional risk of transmission, although this risk is extremely low with suppressive maternal ART. This minimal risk must be balanced with the benefits of breastfeeding for women living with HIV (WLHIV) and their infants. Guidance in high-income countries has evolved, moving towards supported breast feeding for women on suppressive ART. RECENT FINDINGS: Breastmilk transmission accounts for an increasing proportion of new infant infections globally. The majority of transmission data comes from studies including women not on suppressive ART. Breastmilk transmissions in the context of undetectable viral load have rarely occurred, although risk factors remain unclear. Outcome data on supported breastfeeding are accumulating, providing evidence for guidelines and informing infant feeding decisions. Long-acting ART for maternal preexposure prophylaxis or treatment, and infant postnatal prophylaxis are promising future options. SUMMARY: Breastfeeding on suppressive ART has a very low risk of vertical transmission and can have multiple benefits for WLHIV and their infants. However, caution is advised with relaxation of breastfeeding guidance so as not to jeopardise the global goal of elimination of vertical transmission by 2030.
Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Infant , Pregnancy , Female , Humans , Breast Feeding/adverse effects , HIV Infections/drug therapy , Infectious Disease Transmission, Vertical/prevention & control , Risk Factors , HIV Testing , Pregnancy Complications, Infectious/drug therapyABSTRACT
HIV remains a significant public health issue among young adults living in Uganda. There is a need for reliable and valid measures of key psychological and behavioural constructs that are related to important outcomes for this population. We translated, adapted and tested the psychometric properties of questionnaires measuring HIV stigma, HIV disclosure cognitions and affect, antiretroviral therapy (ART) adherence, social support, personal values, and hope, using a multi-step process. This included: translation, back-translation, expert review, cognitive interviewing, readability and assessments of internal consistency with 93 young adults (18-25 years) living with perinatally acquired HIV in Uganda. Preliminary criterion validity was assessed by examining relationships between the adapted measures and wellbeing, HIV disclosure behaviour, HIV disclosure intention and viral load suppression. The measures all showed acceptable reliability and every questionnaire apart from the Agentic and Communal Value Scale was easy to read. Those scales measuring HIV disclosure affect and cognitions, social support, HIV stigma and hope showed relationships with other constructs suggestive of validity. There is preliminary evidence to support the use of these measures in research and clinical contexts for young adults living with perinatally acquired HIV in Uganda.
Subject(s)
HIV Infections , Young Adult , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/psychology , Uganda/epidemiology , Reproducibility of Results , Disclosure , Depression/psychology , Social StigmaABSTRACT
Young adults with perinatally acquired HIV (PAH) face numerous challenges, including antiretroviral therapy (ART) adherence, managing onward HIV transmission risks and maintaining wellbeing. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges but this is difficult. We developed and tested the feasibility of an intervention to help HIV status sharing decision-making for young adults with PAH. The study used a randomised parallel group feasibility design with 18-25-year-olds in Uganda and 18-29 year-olds in the UK. Participants were randomly assigned to intervention or standard of care (SOC) condition. The intervention consisted of four sessions (3 group, 1 individual) with follow-up support, delivered in person in Uganda and remotely in the UK. Assessments were carried out at: Pre-intervention /baseline; Post-intervention (intervention group only); Six-month follow-up. 142 participants were recruited (94 Uganda, 48 UK; 89 female, 53 male). At six-month follow-up, 92/94 (98%) participants were retained in Uganda, 25/48 (52%) in the UK. Multivariate analysis of combined data from both countries, showed a non-significant effect of intervention condition on HIV disclosure cognitions and affect (p = 0.08) and HIV disclosure intention (p = 0.09). There was a significant intervention effect on well-being (p = 0.005). This study addressed important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH across two very different settings. The intervention was acceptable in both countries and feasible in Uganda. In the UK, retention may have been affected by its remote delivery.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019.
Subject(s)
Decision Making , Feasibility Studies , HIV Infections , Humans , Male , Female , Uganda , HIV Infections/psychology , HIV Infections/drug therapy , Adult , United Kingdom , Young Adult , Adolescent , Infectious Disease Transmission, Vertical/prevention & control , Truth Disclosure , Empowerment , Follow-Up StudiesABSTRACT
AIMS: The World Health Organization (WHO) estimates that 3.5% of the population live with hepatitis B virus (HBV); migrants to Europe are disproportionately affected. UK birth dose HBV vaccination is limited to infants born to those living with HBV (LWHBV). High-risk infants (high maternal infectivity, low birthweight) also receive HBV immunoglobulin (HBIG). The Family Hepatitis Clinic follows infants and those LWHBV working towards WHO goals of combating viral hepatitis by 2030. METHODS: A trust-wide electronic note review of outcomes for infants born to those LWHBV (2016-2020). RESULTS: Two hundred and eighty-three infants, 134 (47%) females, born to those LWHBV were referred. Two hundred and thirty-one (82%) attended follow-up with a vertical transmission rate of 0%. Twenty (7%) individuals LWHBV received tenofovir disoproxil fumerate in pregnancy; median viral load (VL) at initiation 125 416 376 DNA IU/mL, one having birth VL. Twenty-eight (10%) infants were stratified as high risk and all received HBIG and birth dose vaccination with 9 (32%) subsequently lost to follow-up, compared to 48 (19%) low-risk infants. 267/283 (94%) had birth dose vaccination documented and 206/283 (73%) received at least four vaccine doses. 215/283 (76%) infants had serology by 24 months; 17 (6%) with suboptimal vaccine responses: hepatitis B surface antibody <100 IU/mL. Serology before 18 months resulted in higher rates of maternal hepatitis B core antibody detection (15% vs. 3%). CONCLUSION: Prevention of vertical transmission of HBV was universal in those attending, although high-risk infants were more likely lost to follow up. HBV post-vaccine serological protection was comparable with national data from 2021 (77% >4 doses, 77% HBsAb >100).
ABSTRACT
The size of the latent HIV reservoir is associated with the timing of therapeutic interventions and overall health of the immune system. Here, we demonstrate that T cell phenotypic signatures associate with viral reservoir size in a cohort of HIV vertically infected children and young adults under durable viral control, and who initiated anti-retroviral therapy (ART) <2 years old. Flow cytometry was used to measure expression of immune activation (IA), immune checkpoint (ICP) markers, and intracellular cytokine production after stimulation with GAG peptides in CD4 and CD8 T cells from cross-sectional peripheral blood samples. We also evaluated the expression of 96 genes in sort-purified total CD4 and CD8 T cells along with HIV-specific CD4 and CD8 T cells using a multiplexed RT-PCR approach. As a measure of HIV reservoir, total HIV-DNA quantification by real-time PCR was performed. Poisson regression modeling for predicting reservoir size using phenotypic markers revealed a signature that featured frequencies of PD-1+CD4 T cells, TIGIT+CD4 T cells and HIV-specific (CD40L+) CD4 T cells as important predictors and it also shows that time of ART initiation strongly affects their association with HIV-DNA. Further, gene expression analysis showed that the frequencies of PD-1+CD4 T cells associated with a CD4 T cell molecular profile skewed toward an exhausted Th1 profile. Our data provide a link between immune checkpoint molecules and HIV persistence in a pediatric cohort as has been demonstrated in adults. Frequencies of PD-1+ and TIGIT+CD4 T cells along with the frequency of HIV-specific CD4 T cells could be associated with the mechanism of viral persistence and may provide insight into potential targets for therapeutic intervention.
Subject(s)
HIV Infections/immunology , HIV-1/physiology , T-Lymphocytes/immunology , Viral Load/physiology , Adolescent , Age of Onset , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/physiology , Child , Cohort Studies , Female , HIV Infections/epidemiology , HIV Infections/virology , Humans , Lymphocyte Activation , Lymphocyte Count , Male , T-Lymphocytes/physiology , Viral Load/immunology , Virus Latency/physiologyABSTRACT
OBJECTIVES: Physicians could request compassionate use of oral and long-acting (LA) cabotegravir + rilpivirine for people living with HIV-1 under a single-patient request programme supported by ViiV Healthcare and Janssen. Outcomes are reported. METHODS: Eligibility criteria included need for parenteral therapy, no primary resistance mutations to cabotegravir or rilpivirine, and established retention in care. Demographic, efficacy, and safety data were obtained from standardized programme applications and quarterly clinical updates. Individuals received a loading dose of LA cabotegravir 600 mg + rilpivirine 900 mg, followed by LA maintenance doses of 400 mg/600 mg every 4 weeks; some received lead-in oral cabotegravir and rilpivirine. RESULTS: Through July 2020, 35 people living with HIV-1 had data available. The most frequent reason for compassionate use request was chronic non-adherence due to psychological conditions (n = 15). Of 35 people living with HIV-1, 28 had detectable viremia (median viral load 60 300 copies/mL) and seven were virologically suppressed at programme entry; 16/28 and 6/7 achieved or maintained virological suppression at data cutoff, respectively. Seven people living with HIV-1 discontinued for incomplete virological response, six with detectable viremia at initiation; six and four had new reverse transcriptase and integrase mutations at discontinuation, respectively. Six non-fatal serious adverse events were reported, two considered possibly treatment related. Four deaths were reported; none were treatment related. One individual reported two pregnancies and continued LA dosing. CONCLUSIONS: Most people living with HIV-1 had advanced disease and achieved (16/28) or maintained (6/7) virological suppression with LA therapy. Cabotegravir LA + rilpivirine LA as compassionate use provided a valuable treatment option for individuals with adherence issues with oral therapy and advanced disease.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV Seropositivity , HIV-1 , Humans , Rilpivirine/pharmacology , Rilpivirine/therapeutic use , HIV Infections/drug therapy , HIV-1/genetics , Compassionate Use Trials , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Viremia/drug therapy , Anti-Retroviral Agents/therapeutic use , HIV Seropositivity/drug therapyABSTRACT
BACKGROUND: The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs). METHODS: 40 PHIV participants initiated ART during infancy. 39 participant samples were available; 30 initiated ART ≤6 months (early-ART treatment); 9 initiated ART >6 months and <2 years (late-ART treatment). We compared plasma cytokine and chemokine concentrations and ADA enzymatic activities between early-ART and late-ART treatment 12.5 years later and measured correlation with clinical covariates. RESULTS: Plasma concentrations of 10 cytokines and chemokines (IFNγ, IL-12p70, IL-13, IL-17A, IL-IRA, IL-5, IL-6, and IL-9 as well as CCL7, CXCL10), ADA1, and ADA total were significantly higher in late-ART compared to early-ART treatment. Furthermore, ADA1 was significantly positively correlated with IFNγ, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFNγ, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7. CONCLUSIONS: Elevation of several pro-inflammatory plasma analytes in late-ART despite 12.5 years of virologic suppression compared to early-ART treatment suggests that early treatment dampens the long-term plasma inflammatory profile in PHIV participants. IMPACT: This study examines differences in the plasma cytokine, chemokine, and ADA profiles 12.5 years after treatment between early (≤6months) and late (>6 months and <2 years) antiretroviral therapy (ART) treatment initiation in a cohort of European and UK study participants living with PHIV. Several cytokines and chemokines (e.g., IFNγ, IL-12p70, IL-6, and CXCL10) as well as ADA-1 are elevated in late-ART treatment in comparison to early-ART treatment. Our results suggest that effective ART treatment initiated within 6 months of life in PHIV participants dampens a long-term inflammatory plasma profile as compared to late-ART treatment.
Subject(s)
HIV Infections , Child , Pregnancy , Female , Humans , HIV Infections/drug therapy , Interleukin-17 , Interleukin-13 , Interleukin-6 , Anti-Retroviral Agents/therapeutic use , Cytokines , ChemokinesABSTRACT
BACKGROUND: Evidence suggests that engagement in care (EIC) may be worse in young people living with perinatal HIV (YPLPHIV) compared to adults or children living with HIV. We took a published EIC algorithm for adults with HIV, which takes patients' clinical scenarios into account, and adapted it for use in YPLPHIV in England, to measure their EIC. METHODS: The adult algorithm predicts when in the next 6 months the next clinic visit should be scheduled, based on routinely collected clinical indicators at the current visit. We updated the algorithm based on the latest adult guidelines at the time, and modified it for young people in paediatric care using the latest European paediatric guidelines. Paediatric/adolescent HIV consultants from the UK reviewed and adapted the resulting flowcharts. The adapted algorithm was applied to the Adolescent and Adults Living with Perinatal HIV (AALPHI) cohort in England. Data for 12 months following entry into AALPHI were used to predicted visits which were then compared to appointment attendances, to measure whether young people were in care in each month. Proxy markers (e.g. dates of CD4 counts, viral loads (VL)) were used to indicate appointment attendance. RESULTS: Three hundred sixteen patients were in AALPHI, of whom 41% were male, 82% of black African ethnicity and 58% born abroad. At baseline (time of AALPHI interview) median [IQR] age was 17 [15-18] years, median CD4 was 597 [427, 791] cells/µL and 69% had VL ≤50c/mL. 10 patients were dropped due to missing data. 306 YPLPHIV contributed 3,585 person months of follow up across the 12 month study in which a clinic visit was recorded for 1,204 months (38/1204 dropped due to missing data). The remaining 1,166 months were classified into 3 groups: Group-A: on ART, VL ≤ 50c/mL-63%(734/1,166) visit months, Group-B: on ART, VL > 50c/mL-27%(320/1,166) Group-C: not on ART-10%(112/1,166). Most patients were engaged in care with 87% (3,126/3,585) of months fulfilling the definition of engaged in care. CONCLUSIONS: The adapted algorithm allowed the varying clinical scenarios of YPLPHIV to be taken into account when measuring EIC. However availability of good quality surveillance data is crucial to ensure that EIC can be measured well.
Subject(s)
Anti-HIV Agents , HIV Infections , Adult , Adolescent , Humans , Male , Child , Female , Patient Participation , HIV Infections/therapy , HIV Infections/drug therapy , England/epidemiology , Ambulatory Care , Viral Load , Algorithms , Anti-HIV Agents/therapeutic useABSTRACT
We compared virological and immunological outcomes for young adults with perinatally-acquired HIV infection (YAPaHIV) in the year preceding, and year of, UK SARS-CoV-2 lockdown restrictions, in a service that maintained face-to-face appointments. Retrospective single-centre cohort analysis from; Period 1(P1) twelve months before the first national lockdown - 23rd March 2019-23rd March 2020, period 2(P2) twelve months of varied restrictions - 24th March 2020-24th March 2021. Data collected from electronic records included age, ethnicity, sex, HIV viral load (VL) (suppression ≤ 200 copies/ml), CD4 count (cells/µL), clinical events, and appointment frequency/modality. Descriptive analysis was comparative between periods. Of 177 YAPaHIV: 56% were female, 86.9% were black, median age at lockdown 23 years (IQR: 21-27). One individual was lost to follow up and excluded from subsequent analysis. 147/176 (83.5%) had a suppressed VL in P1 compared with 156/176 (88.6%) in P2. Of those detectable, median VL was 3200 copies/ml (IQR: 925-36500) in P1, and 911copies/ml (IQR: 317-52300) in P2. In P1, median CD4 was 675 (IQR: 447-845.25). 32(18%) had a CD4 < 350 (median 216.5 [IQR: 94.25-269.75]). 110 (59.5%) had a CD4 count in P2, median 551.5cells/µL (IQR: 329.25-761.25). Thirty one had CD4 < 350 (median 202 [IQR: 134.5-296]). Maintaining face-to-face appointments for vulnerable patients, with remote consultation for stable patients, maintained high levels of care engagement and suppression in a YAPaHIV cohort despite pandemic restrictions.
ABSTRACT
BACKGROUND: Self-harm in adolescents is of growing concern internationally but limited evidence exists on the prevalence of self-harm in those living with HIV, who may be at higher risk of poor mental health outcomes. Therefore our aim was to determine the prevalence and predictors of self-harm among young people with perinatally-acquired HIV (PHIV) and HIV negative (with sibling or mother living with HIV) young people living in England. METHODS: 303 PHIV and 100 HIV negative young people (aged 12-23 years) participating in the Adolescents and Adults Living with Perinatal HIV cohort study completed an anonymous self-harm questionnaire, as well as a number of standardised mental-health assessments. Logistic regression investigated predictors of self-harm. RESULTS: The median age was 16.7 years in both groups, and 40.9% of the PHIV and 31.0% of the HIV negative groups were male. In total 13.9% (56/403) reported having ever self-harmed, with no difference by HIV status (p = 0.089). Multivariable predictors of self-harm were female sex (adjusted odds ratio (AOR) 5.3, (95% confidence interval 1.9, 14.1), p = 0.001), lower self-esteem (AOR 0.9 (0.8, 0.9) per 1 point increase, p < 0.001) and having ever used alcohol (AOR 3.8 (1.8, 7.8), p < 0.001). Self-esteem z-scores for both PHIV and HIV negative participants were 1.9 standard deviations below the mean for population norms. CONCLUSIONS: Self-harm is common among PHIV and HIV negative adolescents in England. Reassuringly however, they do not appear to be at an increased risk compared to the general adolescent population (15-19% lifetime prevalence). The low level of self-esteem (compared to available normative data) in both groups is worrying and warrants further attention.
Subject(s)
HIV Infections/epidemiology , HIV Infections/transmission , Infectious Disease Transmission, Vertical/statistics & numerical data , Self-Injurious Behavior/epidemiology , Adolescent , Child , Cohort Studies , Cross-Sectional Studies , England/epidemiology , Female , Humans , Male , Prevalence , Risk Factors , Self Concept , Surveys and Questionnaires , Young AdultABSTRACT
PURPOSE OF REVIEW: A total of 1.8 million adolescents live with HIV and constitute the only age group in which HIV-associated mortality continues to rise. Meeting their healthcare needs as they transition from paediatric services to adult care is vital for their own health and in prevention of onward transmission to partners and offspring. In this review, we discuss the issues around transition, both within HIV health care and the wider transitions adolescents negotiate as they move out of childhood and into adult life. RECENT FINDINGS: Although transition models vary widely across the globe, the difficulties faced in gathering robust outcome data following transition to adult care and in linkage between paediatric and adult cohorts are universal. Data are particularly sparse for behaviourally infected adolescents outside North America and for key population groups. Poorer health outcomes universal to adolescents may reflect the complex multisystem developmental transition from childhood-to-adulthood, of which transition of healthcare services is a small part. SUMMARY: The complex needs of this generation are well described and whilst examples of good practice are emerging, how best to support their transition to adulthood requires carefully tailored studies of cost-effective interventions that can be up scaled in resource limited settings.
Subject(s)
Continuity of Patient Care , Disease Management , HIV Infections/diagnosis , HIV Infections/drug therapy , Adolescent , Global Health , Health Services Research , Humans , Young AdultABSTRACT
Adolescents with perinatal HIV (PHIV) may be at higher risk of anxiety and depression than HIV negative young people. We investigated prevalence of anxiety and depression symptoms in 283 PHIV and 96 HIV-affected (HIV-negative) young people in England recruited into the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort. We used Hospital Anxiety and Depression Scale (HADS) scores and linear regression investigated predictors of higher (worse) scores.115 (41%) and 29 (30%) PHIV and HIV-affected young people were male, median age was 16 [interquartile range 15,18] and 16 [14,18] years and 241 (85%) and 71 (74%) were black African, respectively. There were no differences in anxiety and depression scores between PHIV and HIV-affected participants. Predictors of higher anxiety scores were a higher number of carers in childhood, speaking a language other than English at home, lower self-esteem, ever thinking life was not worth living and lower social functioning. Predictors of higher depression scores were male sex, death of one/both parents, school exclusion, lower self-esteem and lower social functioning. In conclusion, HIV status was not associated with anxiety or depression scores, but findings highlight the need to identify and support young people at higher risk of anxiety and depression.
Subject(s)
Anxiety/psychology , Depression/psychology , HIV Infections/psychology , Adolescent , Adult , Caregivers , Child , Cohort Studies , England , Female , Humans , Male , Pregnancy , Self Concept , Young AdultABSTRACT
The structure-based design of M-525 as the first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction is presented. M-525 targets cellular menin protein at sub-nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL-regulated gene expression in MLL leukemia cells. M-525 demonstrates high cellular specificity over non-MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co-crystal structure of M-525 in complex with menin firmly establish its mode of action. A single administration of M-525 effectively suppresses MLL-regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M-525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.
Subject(s)
Antineoplastic Agents/pharmacology , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Myeloid-Lymphoid Leukemia Protein/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Antineoplastic Agents/chemistry , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Drug Design , Histone-Lysine N-Methyltransferase/metabolism , Humans , Molecular Dynamics Simulation , Myeloid-Lymphoid Leukemia Protein/metabolism , Protein Interaction Domains and Motifs/drug effects , Protein Structure, Tertiary , Proto-Oncogene Proteins/metabolism , Small Molecule Libraries/chemistry , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Structure-Activity RelationshipABSTRACT
Background: Increasing numbers of children infected perinatally with human immunodeficiency virus (HIV) are surviving to adolescence and transitioning to adult care, yet there are scarce data on their clinical status at transfer. Methods: We analyzed prospective cohort data from the UK/Ireland national Collaborative HIV Pediatric Study (CHIPS). Clinical status at last pediatric clinic visit prior to transfer was described. Factors associated with higher CD4 cell count and viral load (VL) suppression<400 c/mL among patients on antiretroviral therapy (ART) at transfer were assessed using linear and logistic regression, respectively. Data were matched with the UK HIV Drug Resistance Database (UKHIVDRB) to assess cumulative resistance profiles at transfer. Results: Of 1,907 children followed in CHIPS from 1996 to November 2014, 644 (34%) transferred to adult care: 53% were female, 62% born outside the UK/Ireland, 75% black African. At last pediatric follow-up, median age was 17.4 years [interquartile range 16.5,18.1], 27% had previous AIDS diagnosis, CD4 was 444 cells/mm3 [280, 643], 76% were on ART, 13% off-ART, and 11% ART-naive. Among patients on ART, 74% had VL<400 c/mL. In multivariable analysis, higher CD4 at transfer was associated with younger age, higher CD4 at ART initiation and lower VL at transfer (P ≤ .001). Predictors of viral suppression include no AIDS diagnosis and later year of transfer (P ≤ .05). Of 291 patients with resistance data, 82% had resistance to ≥1 drug class, 56% to ≥2 classes and 12% had triple-class resistance. Conclusion: Three-quarters of adolescents were on stable ART at transfer, of whom 74% were virologically suppressed. The prevalence of triple-class resistance was relatively low at 12%.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/epidemiology , HIV Infections/pathology , Adolescent , CD4 Lymphocyte Count , Child , Child, Preschool , Drug Resistance, Viral , Female , HIV/drug effects , HIV/isolation & purification , HIV Infections/drug therapy , HIV Infections/virology , Humans , Infant , Infant, Newborn , Ireland/epidemiology , Male , Prospective Studies , Transition to Adult Care , United Kingdom/epidemiology , Viral LoadSubject(s)
HIV Infections , HIV Seropositivity , HIV-1 , Adult , Humans , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic useABSTRACT
Following the success of antiretroviral therapy, an expanding cohort of adolescents with perinatally acquired HIV (PaHIV) is transitioning into adult care. Dedicated multidisciplinary transitional care HIV services have been established in the UK. However, published data on patient satisfaction with such services are sparse. A single centre survey of patient satisfaction was conducted in January 2014, and results compared to a previous similar survey in 2009. Patients were asked to complete a questionnaire regarding views of their care using a 7-point Likert scale. 51/96 attended within the time period and all completed the survey, compared with 21 in 2009. Ninety-two percent were satisfied with the care provided by the clinic, compared to 100% in 2009. The proportion who felt moving to their current service had a positive effect on their health increased from 68% in 2009 to 81% in 2014. Ninety-two percent were satisfied with the overall care provided by the clinic, compared to 100% in 2009. Ninety-four percent agreed that staff knew how to talk and listen to young people, 96% agreed staff were able to explain their treatments and problems clearly in a way that they could understand. Ninety-six percent felt that a clinic specifically for young people was useful. Despite a marked increase in clinic attendees and unchanged levels of service provision, patient satisfaction remained high. Patients strongly value the provision of dedicated services for young people.
Subject(s)
Continuity of Patient Care/organization & administration , HIV Infections/drug therapy , Patient Satisfaction , Personal Satisfaction , Transition to Adult Care , Adolescent , Adult , Ambulatory Care Facilities , Cohort Studies , Female , HIV Infections/psychology , Health Care Surveys , Humans , Male , Surveys and Questionnaires , United KingdomABSTRACT
BACKGROUND: There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV-) adolescents. METHODS: A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV- adolescents (aged 12-21 and 13-23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV- participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV- participants. Linear regression was performed to explore predictors of NPZ-6. RESULTS: One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV- participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15-18) and 16 (14-18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was -0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), -0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and -0.32 (0.76) in HIV- participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV- participants (adjusted coefficient, -0.01; 95% confidence interval, -.22 to .20). PHIV+/C participants scored below the HIV- group (adjusted coefficient, -0.44; -.70 to -.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores. CONCLUSIONS: Cognitive performance was similar between PHIV+/no C and HIV- participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation.
Subject(s)
Cognitive Dysfunction , HIV Infections/epidemiology , Adolescent , Adult , Anti-Retroviral Agents/therapeutic use , Black People , Child , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Cohort Studies , England/epidemiology , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/physiopathology , HIV-1 , Humans , Infectious Disease Transmission, Vertical , Male , Risk Factors , Young AdultABSTRACT
An increasing number of children born with perinatally acquired HIV (PAH) are surviving into late adolescence and early adulthood. At this developmental stage, forming and sustaining intimate relationships is important. Young adults with PAH face both normative challenges and additional, HIV-related, relationship stressors. One key issue is the decision about whether and how to share their HIV status with others. Being able to disclose one's HIV status to sexual partners may reduce the risk of onward HIV transmission but is associated with the fear of rejection. There has been little research on how young people with PAH manage such disclosure-related stressors in intimate relationships. This study examined how disclosure challenges are managed by young adults with PAH in the UK within their intimate relationships. Seven participants (five females and two males) currently or previously in an intimate relationship, aged 18-23 years, were recruited from a UK hospital clinic. The majority of participants were of sub-Saharan African origins. They took part in in-depth interviews, with data analysed according to the principles of interpretative phenomenological analysis. Four themes were elicited: (1) decisions about starting, continuing or resuming relationships shaped by disclosure, (2) disclosing early to avoid the pain of future rejection, (3) using condoms to avoid disclosure and (4) testing likely partner reactions to disclosure. The study revealed the significant extent to which HIV disclosure affected the experience of relationships in this population. Interventions to support adolescents and young adults with PAH to disclose to their partners should be developed alongside guidance for professionals. Future research should include older samples of adults with PAH and studies in sub-Saharan African settings.