Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.

HIV outcomes during the COVID-19 pandemic in people of Black ethnicities living with HIV in England.

OBJECTIVES: To describe HIV care outcomes in people of Black ethnicities living in England during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic. METHODS: This was an observational cohort study of people of self-reported Black ethnicities attending for HIV care at nine HIV clinics across England. The primary outcome was a composite of antiretroviral therapy (ART) interruption and HIV viraemia (HIV RNA ≥200 copies/mL) ascertained via self-completed questionnaires and review of medical records. We used multivariable logistic regression to explore associations between ART interruption/HIV viraemia and demographic factors, pre-pandemic HIV immunovirological control, comorbidity status, and COVID-19 disease and vaccination status. RESULTS: We included 2290 people (median age 49.3 years; 56% female; median CD4 cell count 555 cells/mm3; 92% pre-pandemic HIV RNA <200 copies/mL), of whom 302 (13%) reported one or more ART interruption, 312 (14%) had documented HIV viraemia ≥200 copies/mL, and 401 (18%) experienced the composite endpoint of ART interruption/HIV viraemia. In multivariable analysis, a pre-pandemic HIV RNA <200 copies/mL (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.15-0.30) and being vaccinated against SARS-CoV-2 (OR 0.41; 95% CI 0.30-0.55) were associated with reduced odds of ART interruption/HIV viraemia; pandemic-related disruptions to HIV care were common self-reported additional factors. CONCLUSIONS: During the COVID-19 pandemic, one in six people of Black ethnicities in this HIV cohort experienced an ART interruption/HIV viraemia. Some of these episodes resulted from pandemic-related healthcare disruptions. Associations with suboptimal engagement in HIV care pre-pandemic and not being vaccinated against SARS-CoV-2 suggest that wider health beliefs and/or poor healthcare access may have been contributory factors.

Clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK.

OBJECTIVES: To describe the clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK. METHODS: We investigated the incidence and factors associated with COVID-19 in a previously established and well-characterized cohort of black people with HIV. Primary outcomes were COVID-19 acquisition and severe COVID-19 disease (requiring hospitalization and/or resulting in death). Cumulative incidence was analysed using Nelson-Aalen methods, and associations between demographic, pre-pandemic immune-virological parameters, comorbidity status and (severe) COVID-19 were identified using Cox regression analysis. RESULTS: COVID-19 status was available for 1847 (74%) of 2495 COVID-AFRICA participants (median age 49.6 years; 56% female; median CD4 cell count = 555 cells/µL; 93% HIV RNA <200 copies/mL), 573 (31%) of whom reported at least one episode of COVID-19. The cumulative incidence rates of COVID-19 and severe COVID-19 were 31.0% and 3.4%, respectively. Region of ancestry (East/Southern/Central vs. West Africa), nadir CD4 count and kidney disease were associated with COVID-19 acquisition. Diabetes mellitus [adjusted hazard ratio (aHR) = 2.39, 95% confidence interval (CI): 1.26-4.53] and kidney disease (aHR = 2.53, 95% CI: 1.26-4.53) were associated with an increased risk, and recent CD4 count >500 cells/µL (aHR = 0.49, 95% CI: 0.25-0.93) with a lower risk of severe COVID-19. CONCLUSIONS: Region of ancestry was associated with COVID-19 acquisition, and immune and comorbidity statuses were associated with COVID-19 disease severity in people of black ethnicity living with HIV in the UK.

Follicle-stimulating hormone in postmenopausal women living with HIV: a prevalence study.

OBJECTIVES: We examined follicle-stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months' amenorrhoea, and investigated correlation with menopausal symptoms. METHODS: A cross-sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months' amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal-Wallis test. RESULTS: Median age was 53 years [interquartile range (IQR): 51-55]; all were on antiretroviral therapy, three-quarters (n = 65) had a CD4 T-cell count > 500 cells/µL and 91.8% (n = 78) had an HIV viral load (VL) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1-78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T-cell count ≥ 200 cells/µL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m2 ). Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37). CONCLUSIONS: Four women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2 . We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months' amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.

Menopausal status, age and management among women living with HIV in the UK.

BACKGROUND: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45-60 years in England. METHODS: Socio-demographic, lifestyle and clinical data were collected through a self-completed cross-sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre-, peri- or post-menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan-Meier survival analysis. RESULTS: The 847 women had a median age of 49 [interquartile range (IQR): 47-52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre-, peri- or post-menopausal, respectively. After adjusting for age, associations of menopausal status with non-cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43-0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20-5.94)] and unemployment [1.34 (0.97-1.84)] remained significant. Median (IQR) age at LMP was 54 (51-55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. CONCLUSIONS: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options.

Prevalence of HIV/hepatitis B and HIV/hepatitis C coinfection among people of East, South, Central and West African ancestry in the United Kingdom.

Regional variability in the prevalence of hepatitis B (HBV) and C (HCV) is reported in sub-Saharan Africa, although data for people with HIV are sparse. We determined the prevalence of HBV/HCV in 2473 people of African ancestry with HIV in the UK. Overall, 6.2% were co-infected with HBV and 1.3% with HCV. Central [adjusted odds ratio (aOR) 2.40 (95% confidence interval (CI) 1.23--4.67) and West [2.10 (1.29-3.41)] African ancestry was associated with HBV and Central [6.98 (2.00-24.43)] African ancestry with HCV.

Over a third of childbearing women with HIV would like to breastfeed: A UK survey of women living with HIV.

The World Health Organisation advice for post-partum women living with HIV (WLHs) in low- and middle-income countries is to breastfeed on suppressive antiretroviral treatment and use infant postnatal prophylaxis. In resource-rich settings, where formula feeding is safe, avoidance of breastfeed is advised. A questionnaire was created to survey attitudes to breastfeeding in WLHs in the United Kingdom. This was offered to all eligible pregnant women in the third trimester or within 3 months post-partum who attended HIV outpatient clinics from 2017 to 2018. Ninety-four women completed the questionnaire, 69% were Black African and 92% had an undetectable HIV viral load. Thirty eight percent stated they would like to breastfeed and 89% said they would breastfeed if they were HIV negative. Sixty two percent had community members question why they did not breastfeed, and 66% felt forced to invent a reason why they were not breastfeeding. Current UK guidelines recommend formula feeding, proposing a harm reduction approach to support women with suppressed HIV who wish to breastfeed. Over a third of respondents said they would like to breastfeed because stigma and secrecy remain an issue for WLHs. This suggests that over time more women may choose this option.

An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well.

Association of HIV status with sexual function in women aged 45-60 in England: results from two national surveys.

Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV.

Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency.

BACKGROUND: To determine patient and treatment characteristics associated with vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort. METHODS: Two hundred twenty-seven HIV-positive patients attending prospectively for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations and other routine chemistry measured. Those with and without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50 nmol/L and >75 nmol/L, respectively. Characteristics were compared between patients with and without VDD. The effects of VDD, tenofovir use, and their interaction on chemical measures were investigated. RESULTS: VDD was found in 57% (131 of 227) of patients. Independent associations included nonwhite ethnicity [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19 (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L) than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir occurred only in the context of VDD. Tenofovir use was not associated with serum creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P = 0.08, respectively), being linked to somewhat higher creatinine and lower eGFR among patients without VDD but higher eGFR in VDD patients. CONCLUSIONS: 25(OH) VDD is associated with tenofovir-linked hyperparathyroidism and also with higher eGFR.