ViiV Healthcare (Spain)

BackgroundOlder persons living with human immunodeficiency virus (PLHIV) have more age-related comorbidities than the general population of PLHIV and greater potential for polypharmacy and drug-drug interactions with antiretroviral treatment (ART). Data comparing the real-world effectiveness of the two-drug dolutegravir/lamivudine (DTG/3TC) and three-drug bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is limited in older PLHIV.MethodsTo assess the real-world effectiveness of switching to DTG/3TC versus BIC/FTC/TAF in older PLHIV, we conducted a retrospective chart review among people aged ≥50 years on ART who were virologically suppressed with ≥24 weeks of follow-up across 7 countries. Index date was defined as DTG/3TC or BIC/FTC/TAF initiation date.ResultsAmong 1144 PLHIV (326 United States, 221 China, 189 Spain, 140 Germany, 113 France, 100 Korea, 55 Taiwan), 593 were on DTG/3TC and 551 were on BIC/FTC/TAF. Demographic and clinical characteristics were similar between groups at index date (Table 1). Among PLHIV on DTG/3TC and BIC/FTC/TAF, 24.6% and 18.7%, were >65 years and 74.5% and 69.7% reported a non-ART comedication, respectively. Prior virological failure was reported in 6.2% of DTG/3TC and 7.7% of PLHIV on BIC/FTC/TAF. Total follow-up was 1463.3 and 1481.9 person-years among DTG/3TC and BIC/FTC/TAF groups, respectively. Approximately 25% of PLHIV had 240 weeks of follow-up. Virological failure was reported for 1 person in each group. The incidence rate of virological failure was 0.07 (95% confidence interval: 0.00-0.14) per 100 person-years for both groups. No resistance was reported.ConclusionIn older, virologically suppressed PLHIV with age-related comorbidities and comedications, switching to either two-drug DTG/3TC or three-drug BIC/FTC/TAF maintained long-term viral suppression without resistance.DisclosuresJeremy Fraysse, MS, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Stocks/Bonds (Private Company) Jennifer Kuretski, DNP, APRN, NP-C, AAHIVS, Gilead Sciences: Speaker|ViiV: Speaker Emilio Letang, MD, MPH, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Maria Jesus Perez Elías, MD, PhD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen Cilag: Advisor/Consultant|Janssen Cilag: Grant/Research Support|Janssen Cilag: Honoraria|ViiV healthcare: Advisor/Consultant|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria Gustavo Verdier, BSc, BPharm, MBA, ViiV Healthcare: Employee Eva Fernvik, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Stocks/Bonds (Private Company) Richard Grove, BSc, MSc, GSK: Stocks/Bonds (Public Company) Cynthia Firnhaber, MD, MS, DTM&H, MERCK: Advisor/Consultant|MERCK: Grant/Research Support Axel Baumgarten, MD, Abbvie: Board Member|Astra Zeneca: Board Member|Gilead: Advisor/Consultant|Gilead: Board Member|Gilead: Honoraria|GSK/ViiV Healthcare: Board Member|Janssen: Board Member|MSD: Board Member|Pfizer: Board Member Bryn Jones, MBChB, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Julie Priest, MSPH, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee

An average time to diagnosis of 7 years is commonly described for endometriosis; diagnostic delay for adenomyosis is unknown. This cross-sectional study aimed to describe diagnostic delay for endometriosis and adenomyosis and to investigate the factors associated with this delay. Community of Patients for Research (ComPaRe)-Endometriosis is a prospective e-cohort of women with endometriosis and/or adenomyosis in France. About 6,949 participants were included. We used linear regression modeling to assess factors associated with diagnostic delay, after adjustment for age, education level, body mass index, number of comorbidities, and family history of the disease or of chronic pelvic pain (CPP). The average diagnostic delay was 10 years for endometriosis and 11 years for adenomyosis. Factors associated with a significantly longer diagnostic delay were year of diagnosis (+0.34 years, p < 0.0001), unemployment (+0.7 years, p = 0.01), number of comorbidities (+0.3 years, p < 0.0001), family history of the disease or of CPP (+1.1 years, p < 0.0001), severe dysmenorrhea before diagnosis (numeric-rating scale: +0.8 years, p < 0.0001), number of health professionals consulted before diagnosis (+0.3 years, p < 0.0001), and presence of multiple symptoms leading to first consultation (+1.6 years, p < 0.0001). In contrast, factors associated with a shorter delay were a financial position perceived as comfortable (-1.4 years, p < 0.0001), age at menarche (-0.6 years, p < 0.0001), and age at first symptoms (-0.8 years, p < 0.0001). This study highlights several factors associated with diagnostic delay among women with self-reported endometriosis and/or adenomyosis and provides new insights to improve care by informing both clinicians and patients. Attention to these profiles may improve disease management.

Dolutegravir (DTG) + lamivudine (3TC) has demonstrated efficacy and safety in phase 3 clinical trials; however, most published data are from people with HIV-1 in North America and Europe. To investigate outcomes from other regions, we summarized real-world outcomes with DTG + 3TC in cohorts from Asia and South America. In this systematic literature review, relevant databases and congresses (2013-2023) were searched to identify non-interventional studies reporting DTG + 3TC use; materials reporting effectiveness, safety, or tolerability outcomes were eligible. Post hoc targeted literature searches explored newer and non-English-language materials. From 218 publications identified, 42 representing 23,512 people using DTG + 3TC (naive to antiretroviral therapy (ART), n = 731; switching ART, n = 3159; unspecified, n = 19,622) in China, Japan, Türkiye, Brazil, Taiwan, Russia, Argentina, and South Korea were included. Most virologic effectiveness outcomes were reported at week 48, with virologic suppression rates ranging from 82% to 100% in people naive to ART and 86% to 100% in those switching ART. Among people initiating DTG + 3TC with very high (≥500,000 copies/mL) baseline viral loads, 64% to 95% achieved virologic suppression at week 48. Virologic failure was infrequent. No treatment-emergent resistance was reported. Serious adverse events (1%) and discontinuations due to adverse events (2%) were infrequent. In real-world cohorts across Asia and South America, initiating or switching to DTG + 3TC resulted in high proportions of people achieving or maintaining virologic suppression and demonstrated a good safety profile at multiple time points, consistent with clinical trial and real-world data in North America and Europe.

Stigma remains a major barrier to accessing HIV care. We analysed the association between stigma and failed pillbox return, and described factors associated with stigma among adults living with HIV in rural Tanzania. From the Kilombero and Ulanga Antiretroviral Cohort we included newly diagnosed adults ≥15 years enrolled between June 2019 and September 2022 with a stigma assessment at 6-12 months and a clinical visit within 7 days. We assessed stigma using the adapted 7-item Berger questionnaire. Logistic and linear regression models were used to identify factors associated with stigma and to determine the association between stigma and depression with failed pillbox return. Among 241 participants (median age 37 years (IQR, 30-44) at enrolment), most were female (n = 170, 71%), WHO stage I (n = 132, 55%), had no pillbox at the clinical visit (n = 188, 78%), and remained in care at 2 years (n = 167, 69%). Participants with no pillbox had slightly higher stigma levels (9, IQR, 5-14) versus those who did (7, IQR, 4-13); this difference was not observed after adjustment (adjusted Odds Ratio 1.02 [95% CI 0.97, 1.07]; p = 0.38). Higher stigma was associated with higher depression (95% CI 0.48, 1.33, p < 0.01), HIV non-disclosure (95% CI 2.58, 8.33, p < 0.01) and higher education (p < 0.01). Higher Body Mass Index (p < 0.01) and advanced WHO stage (p < 0.01) were associated with lower stigma. Failed pillbox return was not associated with stigma. However, stigma was associated with depression, HIV non-disclosure and higher education. Stigma-reduction interventions focused on mental health and disclosure are urgently needed in rural areas.

Longer-term outcome data following second-line antiretroviral therapy initiation in resource-limited settings is limited, especially in regions where genotypic resistance is inaccessible. This analysis evaluated extended efficacy and tolerability data from the D2EFT study. D2EFT is a completed, multicenter, phase IIIB/IV, randomized, open-label trial in 14 low- and middle-income countries. People with human immunodeficiency virus (HIV) who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to 1 of ritonavir-boosted darunavir plus 2 nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r), or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC), with or without pre-switch genotyping. Here we report virological suppression at 96 weeks, defined as HIV RNA <50 copies/mL in a modified intention-to-treat population. Between November 2017 and January 2022, 1190 participants were screened, 828 were randomized, and 826 were included in the analysis. At week 96, the proportions of participants with HIV RNA <50 copies/mL were 191/251 (76.1%) in DRV/r + 2NRTIs, 215/251 (85.7%) in DTG + DRV/r, and 231/283 (81.6%) in DTG + TDF/XTC. The treatment differences (95% confidence intervals [CIs]) in proportions achieving virological suppression were 9.6% (2.7, 16.4) in DTG + DRV/r and 9.0% (1.4, 16.6) in DTG + TDF/XTC, compared to DRV/r + 2NRTIs. Intermediate or high-level dolutegravir resistance was identified in 3/27 (13%) of virological failures in individuals taking DTG + TDF/XTC but in no one taking DTG + DRV/r. No darunavir resistance was observed. After 96 weeks of follow-up, DTG + DRV/r and DTG + TDF/XTC demonstrated virological superiority over DRV/r + 2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG + TDF/XTC, requires ongoing global surveillance.

Switching to dolutegravir plus lamivudine has been associated with weight gain. We aimed to assess factors associated with weight gain and changes in body composition in people with HIV switching to dolutegravir plus lamivudine in the DOLAM trial (EudraCT 201500027435). People with HIV on suppressive triple therapy were randomized to switch to dolutegravir plus lamivudine or to continue triple therapy. Weight and height were measured, and dual X-ray absorptiometry (DXA) scans were performed at baseline and 48 weeks. Factors associated with 48 week weight change were estimated using linear regression models adjusted for weight at baseline. DXA-derived changes were assessed using age- and sex-adjusted linear or log-linear mixed-effects regression models. One hundred and eighty (68% of the DOLAM trial participants) (dolutegravir plus lamivudine, n = 88; triple therapy, n = 92) participants contributed with paired baseline and 48 week DXA scans. Mean (95% CI) weight changes were 1. 362 kg (0.437-2.287) in the dolutegravir plus lamivudine arm and 0.199 kg (-0.742 to 1.140) in the triple therapy arm. Treatment with dolutegravir plus lamivudine and age were independently associated with greater weight change at 48 weeks. DXA-derived changes in body fat mass (<0.5% in both arms), lean mass (<7% in both arms) and bone mineral density scans (<0.5% in both arms) did not differ between arms. Although weight at 48 weeks increased with dolutegravir plus lamivudine but not with triple therapy in the DOLAM study, we did not detect any significant DXA-derived changes in body fat, lean mass or bone mineral density between arms.

BackgroundThe impact of long-term virological suppression (VS) and CD4 count recovery on non–AIDS-defining cancers (NADCs) is unclear. We determined whether poor immune recovery was associated with incident cancer risk in people with human immunodeficiency virus (HIV) with VS.MethodsParticipants from the Data-Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) and International Cohort Consortium of Infectious Disease (RESPOND) collaborations in Europe and Australia who achieved ≥2 years of VS on antiretroviral therapy (ART) between December 1999 and December 2022 were included. Follow-up was from baseline (date of VS for 2 years) until the earliest of a first cancer event, virological failure, final follow-up, or administrative censoring date. Multivariable Poisson regression was used to assess associations between cancer incidence (overall, AIDS-defining cancer, NADC, infection-related cancer, infection-unrelated cancer) and time-updated CD4 count stratified by pre-ART nadir CD4 counts.ResultsOverall, 48 343 people with VS were included (median [interquartile range] baseline age, 43 years [37–50]; CD4 count, 540 cells/µL [380–730]; nadir CD4 count, 245 cells/µL [121–394]; 74% male). There were 1933 incident cancers (median follow-up, 6.2 years [2.9–9.5]; incidence rate [IR], 6.43; 95% confidence interval [CI]: 6.15–6.73/1000 person-years). Higher time-updated CD4 count was associated with a reduced risk of overall cancer (adjusted incidence rate ratio for time-updated CD4 count 350–499 cells/µL: 0.45 [95% CI: 0.39–0.51]; 500–749 cells/µL: 0.30 [95% CI: 0.27–0.34]; and ≥750 cells/µL: 0.26 [95% CI: 0.23–0.30] vs <350 cells/µL; P < .0001). There was a significant reduction in all cancer risk by higher time-updated CD4 count, regardless of nadir CD4 count, with higher pre-ART nadir CD4 count exhibiting lower risk.ConclusionsDespite VS on ART for more than 2 years, people with poorer immune recovery experienced a significantly higher incidence of cancer. This highlights the importance of early HIV diagnosis and ART initiation, and appropriate cancer screening strategies for those with poor immune recovery.