Age-related experiences of diverse older women living with HIV: A scoping review protocol informed by intersectionality.

INTRODUCTION: Older women living with HIV often go unnoticed due to societal biases and stigmas. Despite a rise in cases among older women, there is limited research on the psychosocial factors impacting their experiences. Aging complexities compounded by HIV and menopause affect these women's health, while factors like mental health impact, changing support networks, and ageism with HIV stigma influence their well-being. Existing studies mostly compare older HIV-positive individuals without considering gender and intersectional identities, limiting understanding of their unique experiences. The scarcity of research addressing age-related differences from diverse perspectives delays the development of tailored treatments and interventions. OBJECTIVES: The study aims to comprehensively explore the age-related experiences of older women with HIV through three sub-questions that address (1) Key experiences, medical and social challenges, and strengths; (2) Impact of intersectional identities on their experiences; and (3) Gaps and limitations in current research. METHODS: Utilizing a scoping review approach, the study seeks to map existing literature, employing a theoretical framework rooted in Sex- and Gender-Based Analysis Plus (SGBA+). Articles focusing on the age-related experiences of older women living with HIV aged 50 and above will be included. The study selection process will involve two independent reviewers screening articles based on pre-established inclusion criteria. Data extraction and synthesis will follow, analyzing the influence of sex, gender, and other identities on experiences. DISCUSSION: The study's comprehensive approach aims to bridge gaps in understanding older women's HIV experiences, emphasizing intersectionality. While limited to English-language peer-reviewed articles, this review seeks to offer valuable insights for healthcare, policy, and research, potentially fostering positive change in the lives of diverse older women living with HIV.

Declining Levels of Neutralizing Antibodies to SARS-CoV-2 Omicron Variants Are Enhanced by Hybrid Immunity and Original/Omicron Bivalent Vaccination.

We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15-19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the proportion with detectable neutralizing antibodies to the Omicron variants was decreased, and the levels were lower. Individuals with hybrid immunity at the baseline visit and those receiving the Original/Omicron bivalent vaccine between the two sampling times demonstrated increased neutralizing antibodies to all strains. Both a higher baseline neutralizing antibody titer to Omicron BA.5 and hybrid immunity were associated with protection against a breakthrough SARS-CoV-2 infection during a 4-month period of follow up during the Omicron BA.5 wave. Neither were associated with protection from a breakthrough infection at 10 months follow up. Receipt of an Original/Omicron BA.4/5 vaccine was associated with protection from a breakthrough infection at both 4 and 10 months follow up. This work demonstrates neutralizing antibody escape with the emerging Omicron variants and supports the use of additional vaccine doses with components that match circulating SARS-CoV-2 variants. A threshold value for neutralizing antibodies for protection against reinfection cannot be determined.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Results: Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Conclusions: Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. Clinical trial number: NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

Non-AIDS-defining comorbidities impact health related quality of life among older adults living with HIV.

Introduction: The life expectancy of people living with HIV receiving effective combination antiretroviral therapy is approaching that of the general population and non AIDS-defining age-related comorbidities are becoming of greater concern. In order to support healthy aging of this population, we set out to explore the association between multimorbidity (defined as presence of 2 or more non AIDS-defining comorbidities) and quality of life (QoL). Methods: We performed a cross-sectional analysis using data from the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV age 65 years and older. Study participants completed two QoL modules, the general QoL and health related QoL (HR-QoL). Results: 433 participants were included in the analysis with a median age of 69 years (interquartile range, IQR 67-72). The median number of comorbidities among study participants was 3 (IQR 2-4), with 78% meeting the definition of multimorbidity. General QoL scores (median 66, IQR 58-76) were lower than HR-QoL scores (median 71, IQR 61-83) and were not associated with multimorbidity after adjusting for age, sex, relationship status, household income, exercise, tobacco smoking history, malnutrition, time since HIV diagnosis, and HIV-related stigma. In contrast, multimorbidity was associated with lower HR-QoL (adjusted ß = -4.57, 95% CI -8.86, -0.28) after accounting for the same variables. Several social vulnerabilities (not having a partner, low household income), health behaviours (lower engagement in exercise, smoking), and HIV-related factors (HIV stigma, longer time since HIV diagnosis) were also associated with lower QoL. Discussion: Overall, our study demonstrated a high burden of multimorbidity among older adults living with HIV in Canada, which has a negative impact on HR-QoL. Interventions aimed at preventing and managing non-AIDS-defining comorbidities should be assessed in people living with HIV to determine whether this can improve their HR-QoL.

Frequent Disengagement and Subsequent Mortality Among People With HIV and Hepatitis C in Canada: A Prospective Cohort Study.

Background: The cascade of care, commonly used to assess HIV and hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals' engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people with HIV and HCV. Methods: We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers biannually. Markov multistate models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) reengaged (reentry into cohort after being LTFU); (3) withdrawn from the study (ie, moved); (4) death; otherwise remained (5) engaged-in-care. Results: A total of 1809 participants met the eligibility criteria and contributed 12 591 person-years from 2003 to 2022. LTFU was common, with 46% experiencing at least 1 episode, of whom only 57% reengaged. One in 5 (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (adjusted hazards ratio [aHR], 1.37; 95% confidence interval [CI], 1.13-1.67), evidence of HCV treatment but no sustained virologic response result (aHR, 1.99; 95% CI, 1.56-2.53), and recent incarceration (aHR, 1.94; 95% CI, 1.58-2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Interpretation: Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial.

BACKGROUND: Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). METHODS: This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. FINDINGS: Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per µL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per µL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Correlates of Breakthrough SARS-CoV-2 Infections in People with HIV: Results from the CIHR CTN 328 Study.

COVID-19 breakthrough infection (BTI) can occur despite vaccination. Using a multi-centre, prospective, observational Canadian cohort of people with HIV (PWH) receiving ≥2 COVID-19 vaccines, we compared the SARS-CoV-2 spike (S) and receptor-binding domain (RBD)-specific IgG levels 3 and 6 months post second dose, as well as 1 month post third dose, in PWH with and without BTI. BTI was defined as positivity based on self-report measures (data up to last study visit) or IgG data (up to 1 month post dose 3). The self-report measures were based on their symptoms and either a positive PCR or rapid antigen test. The analysis was restricted to persons without previous COVID-19 infection. Persons without BTI remained COVID-19-naïve until ≥3 months following the third dose. Of 289 participants, 92 developed BTI (31.5 infections per 100 person-years). The median days between last vaccination and BTI was 128 (IQR 67, 176), with the most cases occurring between the third and fourth dose (n = 59), corresponding to the Omicron wave. In analyses adjusted for age, sex, race, multimorbidity, hypertension, chronic kidney disease, diabetes and obesity, a lower IgG S/RBD (log10 BAU/mL) at 1 month post dose 3 was significantly associated with BTI, suggesting that a lower IgG level at this time point may predict BTI in this cohort of PWH.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Predictors of Breakthrough SARS-CoV-2 Infection after Vaccination.

The initial two-dose vaccine series and subsequent booster vaccine doses have been effective in modulating SARS-CoV-2 disease severity and death but do not completely prevent infection. The correlates of infection despite vaccination continue to be under investigation. In this prospective decentralized study (n = 1286) comparing antibody responses in an older- (≥70 years) to a younger-aged cohort (aged 30-50 years), we explored the correlates of breakthrough infection in 983 eligible subjects. Participants self-reported data on initial vaccine series, subsequent booster doses and COVID-19 infections in an online portal and provided self-collected dried blood spots for antibody testing by ELISA. Multivariable survival analysis explored the correlates of breakthrough infection. An association between higher antibody levels and protection from breakthrough infection observed during the Delta and Omicron BA.1/2 waves of infection no longer existed during the Omicron BA.4/5 wave. The older-aged cohort was less likely to have a breakthrough infection at all time-points. Receipt of an original/Omicron vaccine and the presence of hybrid immunity were associated with protection of infection during the later Omicron BA.4/5 and XBB waves. We were unable to determine a threshold antibody to define protection from infection or to guide vaccine booster schedules.