Evaluating virological outcomes in people with HIV on stable antiretroviral therapy with reduced frequency of HIV viral load monitoring during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, HIV outpatient attendances were restricted from March 2020, resulting in reduced frequency of HIV viral load (VL) monitoring (previously 6-monthly) in clinically stable and virologically suppressed people living with HIV (PLWH). We investigated virological outcomes during this period of reduced monitoring and compared with the previous year, prior to the COVID-19 pandemic. METHODS: People living with HIV with undetectable VL (<200 HIV RNA copies /mL) on antiretroviral therapy (ART) were identified from March 2018 to February 2019. We determined VL outcomes during the pre-COVD-19 period (March 2019-February 2020) and the COVID-19 period (March 2020-February 2021) when monitoring was restricted. Frequency and longest durations between VL tests in each period were evaluated, and virological sequelae in those with detectable VL were determined. RESULTS: Of 2677 PLWH virologically suppressed on ART (March 2018-February 2019), VLs were measured and undetectable in 2571 (96.0%) and 2003 (77.9%) in the pre-COVID and COVID periods, respectively. Mean (SD) numbers of VL tests were 2.3 (1.08) and 1.1 (0.83) and mean longest duration between VL tests was 29.5 weeks (SD 8.25, 3.1% were ≥12 months) and 43.7 weeks (12.64, 28.4% were ≥12 months), in the pre-COVID and COVID periods, respectively. Of 45 individuals with one or more detectable VL during the COVID-19 period, two developed new drug resistance mutations. CONCLUSION: Reduced VL monitoring was not associated with poorer virological outcomes in the majority of stable individuals receiving ART. One in 20 individuals had not returned for VL testing after ≥31 months and the risk of harm in these individuals is unknown.

COMMUNITY-BASED, PEER-LED SRH SERVICES INCREASE COVERAGE in AYP (YATHU YATHU TRIAL)

Background: Ensuring adolescents and young people (AYP) have access to comprehensive sexual and reproductive health services (SRHS), including HIV testing and prevention, is critical if we are to reduce HIV incidence and improve wellbeing. Following HPTN 071 (PopART) in Zambia, AYP stated that they needed improved access to SRHS and that these services should be provided from locations other than the health facility. The Yathu Yathu ("For us, by us") trial was co-developed from this request. We report on a secondary outcome of this trial, coverage of 6 predefined key SRHS (HIV testing, ART initiation, PrEP initiation, condom collection, VMMC and hormonal contraception) by trial arm Methods: Yathu Yathu is a cluster randomized trial conducted 2019-2021 in 2 urban communities in Lusaka, Zambia. The communities were divided into 20 zones which were randomly allocated to the Yathu Yathu intervention (YY) or standard of care (SoC) arms. In intervention zones, a YY hub, staffed by supervised peers, provided SRHS. In both arms, a census was conducted in 2019 where AYP (15-24 years) were invited to participate in the trial. Each was offered a Yathu Yathu card, which allowed them to collect "prevention points" for accessing SRHS at the health facility (SoC arm) or at the hub and health facility (YY arm). In both arms, points could be exchanged for health rewards, thus acting as an incentive to access services and as a tool to record service use. We use this YY card data to assess coverage of key SRHS Results: Of the 40,864 AYP enumerated, 29,370 (71.9%) consented to participate and accepted a Yathu Yathu card (14, 872, 71.6% YY arm, 14,498, 72.2% SoC arm). In the YY arm, 9493/14878 (63.8%) accessed at least one key service compared to 775/14498 (5.4%) in the SoC arm (adj RR 12.5;95%CI 9.9-15.8, p<0.001). Results were similar by age and sex (Table 1). The median number of visits in the YY arm was 1 (IQR 0-31) compared to 0 (IQR 0-0) in SoC. Of those accessing any service, HIV testing was the most common service in both arms (8841/9493 (93.1%) and 568/775 (73.3%), respectively) followed by collection of condoms (4701/9493 (49.5%) and 386/775 (49.8%) respectively) Conclusion: The Yathu Yathu intervention increased uptake of key SRHS, especially HIV testing. While YY hubs closed for 3months during COVID-19, health facility attendance may have also decreased thus affecting the difference in coverage. Nonetheless, our findings demonstrate the potential of peer-led community hubs to increase coverage of SRHS.

ChAdOx1 nCoV-19 VACCINATION in PWH: IMMUNE RESPONSES to SARS-CoV-2, VOCs, and HCoVs

Background: People living with HIV (PWH) may represent a high-risk group for adverse clinical outcomes from SARS-CoV-2. The duration of protection from SARS-CoV-2 and emerging variants of concern (VOC) infection in PWH following vaccination is unclear. Furthermore, the role of preexisting SARS-CoV-2 immune responses, likely acquired from prior exposure to circulating human coronaviruses (HCoVs), on vaccine-mediated immunity remains to be determined. Understanding the kinetics of immune responses to SARS-CoV-2 and VOCs, and the impact of preexisting SARS-CoV-2 immunity on vaccine-mediated immune responses will be critical in informing COVID-19 vaccination policies in PWH. Methods: In this sub-study of the Phase II/III COV002 trial (open-label, non-randomised clinical trial ID: NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) and 50 HIV-sex and age-matched controls received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Immune responses to vaccination were determined by ELISA (standard and MSD assay), neutralisation, ACE-2 inhibition, IFNγ ELISpot, activation-induced marker (AIM) assay and T cell proliferation assays. Results: 6 months after vaccination, antibody IgG levels to SARS-CoV-2 S and RBD proteins, ACE-2 inhibition and T cell responses to S protein were significantly higher than baseline (Table 1). Both humoral and cell-mediated immunity waned over time, but with no significant difference compared with HIV-individuals vaccinated with the same regimen. T and B cell-mediated immune responses to VOCs α, β, γ, and δ were detectable, although at lower magnitudes than wild type. Prior exposure to circulating β coronavirus HKU1 and OC43 was associated with measurable proliferative SARS-CoV-2 T cell response at baseline and a higher magnitude of post-vaccine T cell responses. Conclusion: Our data demonstrate no significant difference in ChAdOx1 nCoV-19 vaccine-mediated immune responses by HIV status. For all groups, we show waning but detectable immune responses against SARS-CoV-2 and VOCs 6 months after vaccination supporting the on-going policy to vaccinate against SARS-CoV-2 and reinforces the argument for long-term monitoring of responses.

Sexual and reproductive health needs for young women living with perinatally acquired HIV through the pandemic

Background: Lockdown and reconfiguration of NHS services imposed to limit the spread of SARS-CoV- 2 led to significantly reduced uptake of routine NHS care including access to cervical screening, contraceptive and sexual health services. We describe female sexual and reproductive health of a cohort of young women living with perinatally acquired HIV (YWLPaHIV) over the time-period covering SARS-CoV- 2 restrictions. Method: Single-centre observational cohort review of sexual and reproductive health for YWLPaHIV attending HIV services 01.07.2020 to 01.01.2021. Data collected included demographics, age of menarche/coitarche, Human papillomavirus (HPV) and Hepatitis B virus (HBV) vaccination, contraception, past sexually transmitted infections (STIs), cervical screening and obstetric history. Analysis was descriptive, with categorical analysis of qualitative data. Primary aim was to identify individuals in need of contraception, cervical screening and HBV vaccination/boosting. Results: 71 YWLPaHIV median age 23 years (IQR 21-27), 87% of black ethnicity, average body mass index 25.9kg/m2 (SD 5.6) with 58/71 (82%) latest viral load <200 copies/ml. Median age at menarche 13 years (IQR 12-14) with 5/64 (8%) reporting delayed puberty (menarche316 years). 51/71 (72%) reported coitarche, average age 17.6 years. 24 women reported 45 pregnancies;16/45 (36%) live births (all infants HIV-negative), 19(42%) terminations, 7(16%) miscarriages and 3(7%) current pregnancies. Excluding pregnant women;31/48 (65%) reported current contraception;10 (32%) condoms, 8(26%) intrauterine systems, 7(23%) Depo-Provera, 4(13%) implant and 3(10%) oral contraceptive pill. 18/51 (35%) reported previous STIs;HPV (11), chlamydia (9), Herpes Simplex (2). 27/71 (38%) reported ever having a cervical smear including 20/28 (71%) women aged 25 or older, 15(54%) within 3.5 years (national average 69%). Abnormal findings reported in 7/27 (26%) included 5 CIN1 and 3/27 (11%) were HPV positive. 59/71 (83%) recalled prior HPV vaccination. Excluding four YWPaHIV with HBV coinfection, 41/63 (71%) demonstrated HBV surface antibodies >10mIU. Conclusion: In this small cohort cervical smear uptake was below the national average despite high levels of previous abnormal findings. Given the high rates of prior STIs and pregnancy terminations, addressing the contraceptive and sexual health needs including vaccination for young women, may require accessible face-2- face services despite the pandemic.

HIV and COVID-19 inpatient outcomes: A matched retrospective multicentre analysis

Background: Clinical outcomes for people living with HIV (PLWH) hospitalized with COVID-19 infections have shown mixed outcomes. We conducted a multicentre, UK retrospective matched cohorts' analysis. Methods: Index cases were HIV+ COVID-19 PCR+ patients hospitalized between dates 1st February - 31st May 2020. HIV-negative patients were matched to PLWH up to a 3:1 ratio across 6 sites in England, by hospital site, test date +/- 7 days, age +/- 5 years, gender, index of multiple deprivation decile (IMDD) +/- 1. The primary outcome was patients achieving ≥2-point improvement on a 7-point ordinal scale or discharge from hospital by day 28, whichever was earlier. Follow up was right-censored at day 28 for patients still in hospital. Baseline characteristics and outcomes were analysed by Coxproportional hazards regression stratified by matching clusters using multiple imputation for missing data. The model adjusted for ethnicity, clinical frailty score, body mass index, baseline hypoxia, duration of symptoms, hypertension, diabetes, malignancy, cardiac, lung and renal disease. Results: 68 PLWH and 181 HIV-negative patients were included. PLWH had an HR of 0.57 (95%CI 0.39, 0.85;p=0.005) of achieving 2-point improvement or discharge compared to HIV-negative patients. The effect size of HIV-status was attenuated (aHR 0.70;0.43, 1.17;P=0.18) after adjustment in the multivariable model (Table 1), with baseline frailty (aHR=0.79;95%CI 0.65, 0.95;p=0.011 ), malignancy (aHR=0.37;95%CI 0.17, 0.82;p=0.014) having a greater impact on the primary outcome. Proportion of deaths (19.1% vs 19.3%, p=0.266) and patients requiring ventilation (23.5% vs 17.1%, p=0.25) were similar between PLWH and HIV-negative patients. Sensitivity analyses adjusting for age and excluding missing data, remained consistent with main findings. PLWH were frailer (median clinical frailty score 3 vs 2, p=0.0069), and had higher proportion of malignancies (14.7% vs 9.9%, p=0.29) although not statistically significant. Number of non-HIV co-morbidities (2 vs 2, p=0.16) and median BMI (27.7 vs 29.4, p=0.19) were similar. The median CD4 count of PLWH was 352cells/ μL (IQR 235, 619), and 63/68 (92.3%) were taking antiretroviral therapy. Conclusion: Although PLWH were less likely to achieve improvement or discharge, after adjustment the effect of HIV-status was attenuated. Increased baseline frailty and active malignancies remain associated with poorer COVID-19 outcomes.

HIV cure research in the time of COVID-19 - Antiretroviral therapy treatment interruption trials: A discussion paper.

This discussion paper addresses the safety of HIV cure studies, particularly those involving stopping antiretroviral therapy, known as an analytic treatment interruption (ATI) in the context of the SARS-CoV-2 pandemic. More than 30 studies listed on ClinicalTrials.gov include an ATI and many others were planned to begin over the next 12 months but most were halted due to the COVID-19 pandemic. We consider the ethics, risks and practical considerations to be taken into account before re-opening HIV cure clinical trials, noting the specific risks of ATI in the context of circulating SARS-CoV-2.