Differences in HIV clinical outcomes amongst heterosexuals in the United Kingdom by ethnicity

OBJECTIVE: We investigated differences in clinical outcomes in heterosexual participants, by ethnicity in the UK Collaborative HIV Cohort Study from 2000-2017. DESIGN: Cohort analysis. METHODS: Logistic/Proportional hazard regression assessed ethnic group differences in CD4+ cell count at presentation, engagement-in-care, combination antiretroviral therapy (cART) initiation, viral suppression and rebound. RESULTS: Of 12,302 participants (median age: 37 [interquartile range: 31, 44] years, 52.5% women, total follow-up: 85,846 person-years), 64.4% were Black African, 19.1% White, 6.3% Black Caribbean, 3.6% Black Other, 3.3% South Asian/Other Asian and 3.4% Other/Mixed. CD4+ cell count at presentation amongst participants from non-White groups were lower than the White group. Participants were engaged-in-care for 79.6% of follow-up time, however Black and Other/Mixed groups were less likely to be engaged-in-care than the White group (adjusted odds ratios vs. White: Black African: 0.70 [95% confidence interval 0.63, 0.79], Black Caribbean: 0.74 [0.63, 0.88], Other/Mixed: 0.78 [0.62, 0.98], Black Other: 0.81 [0.64, 1.02]). Of 8,867 who started cART, 79.1% achieved viral suppression, with no differences by ethnicity in cART initiation or viral suppression. Viral rebound (22.2%) was more common in the Black Other (1.95 [1.37, 2.77]), Black African (1.85 [1.52, 2.24]), Black Caribbean (1.73 [1.28, 2.33]), South Asian/Other Asian (1.35 [0.90, 2.03]) and Other/Mixed (1.09 [0.69, 1.71]) groups than in White participants. CONCLUSIONS: Heterosexual people from Black, Asian and minority ethnic groups presented with lower CD4+ cell counts, spent less time engaged-in-care and were more likely to experience viral rebound than White people. Work to understand and address these differences is needed

Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART)

HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

BACKGROUND: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. OBJECTIVES: We examined darunavir DRMs emerging in clinical practice in the UK. PATIENTS AND METHODS: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. RESULTS: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. CONCLUSIONS: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility

Evolution of CD4 T-Cell count with age in a cohort of young people growing up with perinatally acquired HIV

Background: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired HIV (PHIV). We examine changes and predictors of CD4 over time in PHIV in the UK and compare to published CD4 data in the general population.// Methods: PHIV followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onwards were included. Follow-up data from the UK Collaborative HIV Cohort Study were also used. Changes in CD4 count over time from age 10 to 20 years were analysed using mixed effects models. Potential predictors included demographics, age at ART start, nadir CD4 z-score (age-adjusted) in childhood and time-updated viral load.// Results: Of 1,258 PHIV included, 669 (53%) were female, median [IQR] age at ART initiation was 8.3 years [3.5, 12.1] and nadir CD4 z-score was -4.0 [-5.9, -2.5]. In multivariable analysis, mean CD4 count was higher in PHIV who started ART before age 10 and had a nadir CD4 z-score ≥-4 in childhood; these PHIV had a decline in CD4 count after age 10 which was comparable to the general population. Mean CD4 count was lower in PHIV who had started ART before age 10 and had a nadir CD4 z-score <-4 in childhood; for this group the decline in CD4 count after age 10 was steeper over time.// Conclusions: In children, as well as starting ART at an early age, optimising ART to maintain a higher CD4 z-score during childhood may be important to maximize immune reconstitution later in life

Response to antiretroviral therapy (ART): comparing women with previous use of zidovudine monotherapy (ZDVm) in pregnancy with ART naïve women.

Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started

HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era

BACKGROUND AND PURPOSE Data describing the incidence and survival of HIV-related central nervous system diseases (CNS-D) in recent years are sparse. METHODS Between 1996 and 2007, adult subjects without previous CNS-D within a large UK cohort were included (n=30,954). CNS-D were HIV encephalopathy (HIVe), progressive multifocal leucoencephalopathy (PML), cerebral toxoplasmosis (TOXO) and cryptococcal meningitis (CRYP). Associations between demographic, clinical and laboratory parameters with incidence and survival of CNS-D were evaluated using Poisson regression analysis and Kaplan-Meier techniques. RESULTS Six hundred and thirteen new CNS-D occurred in 574 subjects (HIVe:187, PML:113, TOXO:184, CRYP:129). Incidence of all CNS-D declined from 13.1 per 1000 PY in 1996/1997 to 1.0 per 1000 PY in 2006/2007 (P=0.0001). Current CD4+ cell count below 200 cells/ul and plasma HIV RNA above 100,000 copies/ml were independently associated with the development of CNS-D. Calendar year 1996/1997, older age, prior AIDS diagnosis and PML diagnosis were significantly associated with shorter survival. CONCLUSIONS An ongoing decline in the incidence of CNS-D has been observed in very recent years. Mortality following such a diagnosis remains high

Incidence and risk factors for tuberculosis among people with HIV on antiretroviral therapy in the UK

OBJECTIVE: The UK has a low tuberculosis incidence and earlier combination antiretroviral therapy (cART) is expected to have reduced incidence among people with HIV. Epidemiological patterns and risk factors for active tuberculosis were analysed over a 20 year period among people accessing HIV care at sites participating in the UK CHIC observational study. DESIGN: Cohort analysis. METHODS: Data were included for individuals over 15 years old attending for HIV care between 1996 and 2017 inclusive, with at least three months follow up recorded. Incidence rates of new tuberculosis events were calculated and stratified by ethnicity (white/black/other) as a proxy for tuberculosis exposure. Poisson regression models were used to determine the associations of calendar year, ethnicity and other potential risk factors after cART initiation. RESULTS: 58,776 participants (26.3% female; 54.5% white, 32.0% black, 13.5% other/unknown ethnicity; median (interquartile range) age 34 (29-42) years) were followed for 546,617 person-years. 704 were treated for active tuberculosis (rate 1.3 [95% confidence interval (CI) 1.2-1.4]/1000 person-years). Tuberculosis incidence decreased from 1.3 [1.2-1.5] to 0.6 [0.4-0.9]/1000 person-years from pre-2004 to 2011-2017. The decline among people of black ethnicity was less steep than among those of white/other ethnicities, with incidence remaining high among black participants in the latest period (2.1 [1.4-3.1]/1000 person-years). 283 participants (191 (67%) black African) had tuberculosis with viral load < 50 copies/ml. CONCLUSIONS: Despite the known protective effect of cART against tuberculosis, a continuing disproportionately high incidence is seen among black African people. Results support further interventions to prevent tuberculosis in this group

Patterns of retention in clinical care among HIV-positive men in the UK CHIC Study

We examined disparities in engagement and retention-in-care among men in the UK Collaborative HIV Cohort (CHIC) Study according to ethnic group and mode of HIV infection. All male subjects in UK CHIC from 1996&#x2013;2011 were included. We considered factors associated with both initial engagement (follow-up&#x003E;1 day) and consistent retention in care (no interval between consecutive CD4/viral load (VL) measures&#x003E;6 months). Logistic regression was used to identify associations with ethnic group and mode of HIV infection after adjusting for covariates at study entry (age, year, use of antiretrovirals (ART), AIDS). Analyses of retention also adjusted for VL/CD4 at entry and clinic. The 33210 men had a median (interquartile range) age of 36 (30,42) years at study entry, ethnic group was white (21851, 65.8%), black African (4374, 13.2%), black other (1539, 4.6%), Asian (967, 2.9%), other (2337, 7.0%) and unknown (2142, 6.5%). Mode of infection was sex between men (MSM) (22260, 67.0%), heterosexual sex (HET) (6286, 18.9%), other (1556, 4.7%) and unknown (3108, 9.4%). 32045 (96.5%) men were initially engaged in care, with no major differences by ethnic group after adjustment. Compared to MSM, initial engagement was less likely in those with heterosexual (adjusted odds ratio 0.77 [95% confidence interval 0.63&#x2013;0.95]) or other (0.43 [0.33&#x2013;0.56]) modes of infection. Other factors associated with initial engagement were older age, receipt of ART and having AIDS at entry; those entering UK CHIC in 2008&#x2013;2011 were less likely to engage due to the shorter follow-up time. Of the men initially engaged in care, 12644 (44.0%) were consistently retained with no interval between consecutive CD4/VL&#x003E;6 months. Consistent retention was more likely in MSM than in those with other modes of infection (HET: 0.76 [0.68&#x2013;0.84]; other 0.54 [0.46&#x2013;0.62]). Ethnic group again did not impact greatly on subsequent retention. Other independent predictors of retention were older age, receipt of ART and AIDS at entry. Those entering UK CHIC in later years were more likely to exhibit consistent retention as were those with higher VL and lower CD4 at entry. Our study demonstrates high rates of initial engagement in care. Those infected with HIV through heterosexual sex and younger men are less likely to engage in care and, once engaged, are less likely to attend consistently. The reasons behind these differences need to be explored further to ensure equitable health care delivery