Reported Side Effects and Adherence of Daily HIV Pre-Exposure Prophylaxis Users in Ontario, Canada: An Analysis of the Ontario Pre-Exposure Prophylaxis Cohort Study.

Side effects are a common concern of current and potential HIV pre-exposure prophylaxis (PrEP) users, potentially leading to missed doses. We examined the relationship between reported side effects and adherence in the Ontario PrEP Cohort Study (ON-PrEP). In total, 600 predominantly gay (87.3%), White (65.8%), and male (95.0%) participants completed questionnaires assessing the presence and severity of five side effect categories (nausea, diarrhea, headache, abdominal pain, and "other") as well as their adherence to daily PrEP (any missed doses in the previous 4 days). In total, 175 participants (29%) ever reported experiencing side effects: most commonly diarrhea (7.5% of study visits), and most were of mild severity. Lower incomes (p = 0.01), identifying as bisexual (p = 0.04), and baseline concern about side effects (p < 0.001) were associated with ever reporting side effects. The odds of reporting any side effects decreased by a factor of 0.44 (95% confidence interval 0.25-0.80) with each additional year of PrEP use, however 1 in 10 participants still reported side effects after 1 year of use. The odds of reporting optimal adherence were 0.48 (0.28-0.83) times lower for participants reporting any side effects, 0.67 (0.51-0.89) times lower per additional side effect category reported, and 0.78 (0.65-0.97) times lower per incremental increase in side effect severity ratings. We found some evidence of interaction between side effect measures and duration of PrEP use, suggesting that these relationships were stronger for participants taking PrEP for longer. Clinicians should make efforts to ascertain patients' experience of side effects and consider risk counseling and alternative PrEP regimens to promote adherence.

Lower PrEP Retention among Young and Black Clients Accessing PrEP at a Cluster of Safety Net Clinics for Gay and Bisexual Men.

Young men of color who have sex with men are vulnerable to HIV and experience poor PrEP uptake and retention. We conducted a secondary data analysis and calculated adjusted Prevalence Odds Ratios (aPORs) for PrEP retention along with 95% CIs at 90, 180, and 360 days at an organization running safety net clinics in Texas for gay and bisexual men. We found statistically significant association with age, race, in-clinic versus telehealth appointments, and having healthcare insurance. White clients had an aPOR of 1.29 [1.00, 1.67] as compared to Black clients at 90 days. Age group of 18-24 had a lower aPOR than all other age groups except 55 or older at all three time periods. Clients who met providers in person had an aPOR of 2.6 [2.14, 3.19] at 90, 2.6 [2.2, 3.30] at 180 days and 2.84 [2.27, 3.54] at 360 days. Our findings highlight the need for population-specific targeted interventions.

Lower PrEP retention for black and young MSM in TexasOur study findings suggest that of all clients who start PrEP, Black clients and younger clients had a higher chance of not continuing PrEP as compared to White clients and older clients respectively. This analysis was done for a clinic that pre-dominantly offers services to gay and bisexual men. We also found that those who were attending clinic in person had higher chances of continuing. Further those who are insured also had higher chances of continuing.

Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting.

BACKGROUND: Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). METHODS: This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. RESULTS: Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by - 0.04 mg/dL (95% confidence interval [CI]: - 0.07 to - 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV. CONCLUSIONS: Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important.

Knowledge and Attitudes About HIV Pre-Exposure Prophylaxis Among Sexually Active Black and Latina Cisgender Women: Findings from the 2017 and 2018 New York City Sexual Health Survey.

Pre-exposure prophylaxis (PrEP) is a highly effective tool to prevent HIV, yet it is underutilized among women. The current study aims to evaluate the awareness, attitudes, and perceptions of PrEP among a large survey sample of Black and Latina women in New York City (NYC). Interviewer-administered surveys were conducted in high HIV incidence neighborhoods in NYC among Black, Latina, and Afro-Latina women who reported recent sex with a man in 2017 (n = 398) and 2018 (n = 405). About 40% of participants were aware of PrEP, whereas 30.4% indicated interest in using it. The top reason for not utilizing it was low HIV risk perception. However, most participants supported the idea that using PrEP meant asserting control over their health (94.1%). Primary care providers and obstetricians/gynecologists were participants' preferred sources for PrEP (91.6%). Across survey cycles, compared to non-Black Latina participants, Black participants had significantly higher PrEP awareness (44.4% vs. 29.1%). PrEP awareness was also significantly higher among survey participants in 2018 (45.2%) than in 2017 (34.3%). Less than half of the participants were aware of PrEP, but those who were aware expressed largely positive attitudes toward the medication. Our findings may inform future PrEP implementation strategies to optimize awareness and access to PrEP among women disproportionately affected by HIV, like focusing on personal empowerment instead of risk-based messaging and training women's sexual health care providers in PrEP provision.

A qualitative study on reasons for women's loss and resumption of Option B plus care in Ethiopia.

Loss to follow-up (LTFU) from Option B plus, a lifelong antiretroviral therapy (ART) for pregnant women living with human immunodeficiency virus (HIV), irrespective of their clinical stage and CD4 count, threatens the elimination of vertical transmission of the virus from mothers to their infants. However, evidence on reasons for LTFU and resumption after LTFU to Option B plus care among women has been limited in Ethiopia. Therefore, this study explored why women were LTFU from the service and what made them resume or refuse resumption after LTFU in Ethiopia. An exploratory, descriptive qualitative study using 46 in-depth interviews was employed among purposely selected women who were lost from Option B plus care or resumed care after LTFU, health care providers, and mother support group (MSG) members working in the prevention of mother-to-child transmission unit. A thematic analysis using an inductive approach was used to analyze the data and build subthemes and themes. Open Code Version 4.03 software assists in data management, from open coding to developing themes and sub-themes. We found that low socioeconomic status, poor relationship with husband and/or family, lack of support from partners, family members, or government, HIV-related stigma, and discrimination, lack of awareness on HIV treatment and perceived drug side effects, religious belief, shortage of drug supply, inadequate service access, and fear of confidentiality breach by healthcare workers were major reasons for LTFU. Healthcare workers' dedication to tracing lost women, partner encouragement, and feeling sick prompted women to resume care after LTFU. This study highlighted financial burdens, partner violence, and societal and health service-related factors discouraged compliance to retention among women in Option B plus care in Ethiopia. Women's empowerment and partner engagement were of vital importance to retain them in care and eliminate vertical transmission of the virus among infants born to HIV-positive women.

Provider Perspectives on Rapid Treatment Initiation Among People Newly Diagnosed With HIV: A New Message of "Urgency"?

BACKGROUND: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. METHODS: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. RESULTS: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. CONCLUSION: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.

Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIVTreating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately.

Courier delivery of antiretroviral therapy: a cohort study of a South African private-sector HIV programme.

INTRODUCTION: Courier delivery has become a popular antiretroviral therapy (ART) distribution method in some HIV care settings, yet data on ART courier delivery and how it relates to ART outcomes are scarce. We studied the differences in viral suppression rates between individuals from a South African private sector HIV programme receiving ART by courier delivery and those receiving ART through traditional retail dispensing. METHODS: Individuals aged 15 years or older who were actively enrolled in the Aid for AIDS programme between January 2011 and July 2022 were eligible for the analysis. The outcome of interest was viral suppression defined as a viral load (VL) <400 copies per ml. We calculated adjusted odds ratios (OR) for the association between the ART distribution method and viral suppression, comparing those receiving refills through courier pharmacies versus retail dispensing at the time of the VL testing. We used generalized estimating equations to account for repeated VL testing of the same individual. The models were adjusted for age, sex, calendar year, ART regimen, history of mental illness and medical insurance scheme. We computed adjusted ORs for the calendar periods 2011-2013, 2014-2016, 2017-2019, 2020-2022 and overall. RESULTS: We extracted 442,619 VL measurements from 68,720 eligible individuals, 39,406 (57.3%) were women. The median number of VL measurements per individual was 6 (IQR 3-10). VL suppression was detected in 398,901 (90.1%) tests, and 185,701 (42.0%) of the tests were taken while the individual was receiving ART by courier delivery. Overall, courier delivery was associated with 5% higher odds of viral suppression than retail dispensing (adjusted OR 1.05, 95% CI 1.02-1.08). The strength and direction of this association varied by calendar period, with an adjusted OR of 1.37 (95% CI 1.27-1.48) in 2011-2013 and 1.02 (95% CI 0.97-1.07) in 2020-2022. CONCLUSIONS: Courier delivery of ART is a viable alternative to retail dispensing in the South African private sector, as it was associated with higher viral suppression until 2016 and similar suppression rates in recent years. Further research is needed to investigate the potential benefits and drawbacks of courier delivery of ART in both private and public healthcare settings.

Adaptation and validation of the Adherence Barriers Questionnaire for HIV Patients on Antiretroviral Therapy (ABQ-HIV) for the Brazilian context.

Despite significant advancements in antiretroviral therapy (ART) for HIV, adherence remains a challenge. While Brazil has validated scales for treatment adherence, few assess treatment adherence barriers. This underscores the necessity for validated questionnaires on adherence barriers to identify patient-specific challenges and enhance strategies for ART adherence. This study aimed to adapt and validate the Adherence Barriers Questionnaire for HIV Patients on Antiretroviral Therapy (ABQ-HIV), a 17-item questionnaire assessing the adherence barriers to ART, for the Brazilian context and to evaluate its psychometric properties in HIV patients. A methodological study on the psychometric properties and factorial structure of ABQ-HIV was conducted. The study followed seven steps: consent of the original authors, two translations, synthesis of the translations, expert committee, back-translation, pre-test, and reliability test. A high content validity index (0.93) was achieved with the expert committee. The study sample consisted of 230 adults with HIV, with 37.0 (29.3-45.0) years as the median age (IQR), and 52.2% were male. The exploratory factor analysis with a three subscales structure of 17 items showed good interpretability (Bartlett's sphericity (1167.2 [136]; p < 0.001) and Kaiser-Meyer-Olkin = 0.602) and internal consistency (α = 0.76; Ω = 0.76). The fit indicators were satisfactory (χ2 = 89.931; df = 88; p > 0.005; RMSEA = 0.010; RMSR = 0.07; CFI = 0.996; GFI = 0.940; AGFI = 0.907; NNFI = 0.995). The Brazilian version of ABQ-HIV is a potential instrument for identifying specific barriers to adherence to ART in adults living with HIV in Brazil.

Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.

BACKGROUND: People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence. METHODS: A5314 was a phase 2 randomized, double-blind, multicenter trial in 176 adult people with HIV-1 on virally suppressive antiretroviral therapy. LDMTX (5-15 mg/wk) was administered for 24 weeks with an additional 12 weeks of participant follow-up. The current analyses of HIV-1 persistence were restricted to 60 participants (30 LDMTX and 30 placebo) randomly selected from the total population. Plasma HIV-1 RNA, total HIV-1 DNA, and cell-associated HIV-1 RNA (CA HIV-1 RNA) were measured by sensitive quantitative PCR assays. RESULTS: LDMTX treatment had no significant effect on sensitive measures of plasma HIV-1 RNA, HIV-1 DNA, CA HIV-1 RNA, or CA HIV-1 RNA/DNA ratio at any time point or from baseline to week 24. As observed in the main study, absolute peripheral CD4+ and CD8+ T-cell numbers decreased from baseline to week 24 among the 30 participants receiving LDMTX compared with placebo (median decrease of -31.5 CD4+ T cells/µL, -83.5 CD8+ T cells/µL). CONCLUSIONS: LDMTX had no significant effect on any measure of HIV-1 persistence in plasma or peripheral blood mononuclear cells. Further studies are needed to determine whether other immunosuppressive and/or immunoreductive interventions are safe and capable of affecting HIV-1 persistence.

Brief Report: Group-Based Trajectory Modeling to Determine Long-Term HIV Viral Load Trends Among Children With HIV in Kenya.

BACKGROUND: Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of nonadherence among children. METHODS: Children under 12 months old who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV therapy cohort (NCT00428116) from 2007 to 2010. Children initiated antiretroviral therapy at enrollment, and VL was assessed every 3 months for 24 months post-antiretroviral therapy and every 6 months thereafter up to 8 years old. VL trajectory groups were defined using GBTM. Fisher's exact and Kruskal-Wallis tests were used to determine the correlates of each trajectory group compared with the sustained-low VL group. RESULTS: Five VL trajectory groups were identified among 89 children with 522 VL visits from 6 to 24 months: sustained-low (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; P = 0.03) and had younger caregivers (median: 22 vs 28 years; P = 0.02). Among 54 children with 560 VL visits followed from 48 to 96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; P = 0.01). CONCLUSIONS: GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of nonsuppression. Younger caregivers may benefit from tailored counseling to help them support child antiretroviral therapy adherence. Palatable regimens are necessary for viral suppression among children with HIV.

Exploring Co-Amorphous Formulations Of Nevirapine: Insights From Computational, Thermal, And Solubility Analyses.

This study aimed to assess the formation of nevirapine (NVP) co-amorphs systems (CAM) with different co-formers (lamivudine-3TC, citric acid-CAc, and urea) through combined screening techniques as computational and thermal studies, solubility studies; in addition to develop and characterize suitable NVP-CAM. NVP-CAM were obtained using the quench-cooling method, and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and polarized light microscopy (PLM), in addition to in vitro dissolution in pH 6.8. The screening results indicated intermolecular interactions occurring between NVP and 3TC; NVP and CAc, where shifts in the melting temperature of NVP were verified. The presence of CAc impacted the NVP equilibrium solubility, due to hydrogen bonds. DSC thermograms evidenced the reduction and shifting of the endothermic peaks of NVP in the presence of its co-formers, suggesting partial miscibility of the compounds. Amorphization was proven by XRD and PLM assays. In vitro dissolution study exhibited a significant increase in solubility and dissolution efficiency of NVP-CAM compared to free NVP. Combined use of screening studies was useful for the development of stable and amorphous NVP-CAM, with increased NVP solubility, making CAM promising systems for combined antiretroviral therapy.

PREVALENCE OF DIDANOSINE-RELATED RETINAL TOXICITY AT AN URBAN ACADEMIC CENTER AS DIAGNOSED WITH ULTRA-WIDEFIELD IMAGING.

PURPOSE: Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. METHODS: This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. RESULTS: Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. CONCLUSION: This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.

An optimized strategy triggered at the 2nd immunization visit to prevent HIV acquisition by breastfeeding: a phase 2 trial in Burkina Faso (PREVENIR-PEV).

BACKGROUND: Mother-to-child transmission of HIV during breastfeeding remains a challenge in low- and middle-income countries (LMIC). A prevention package was initiated during the highly attended 2nd visit of the Expanded Program of Immunisation (EPI-2) to identify the undiagnosed infants living with HIV and reduce the postnatal transmission of infant exposed to HIV. METHODS: PREVENIR-PEV is a non-randomized phase II clinical trial conducted at two health centres in Bobo Dioulasso (Burkina Faso). The study recruited mothers living with HIV aged 15 years and older with their singleton breastfed infants. During EPI-2 (at 8 weeks) and upon signature of the informed consent, a point-of-care early infant diagnosis (EID) was performed. HIV exposed uninfected (HEU) infants were followed-up until 12 months of age. High risk HEU infants (i.e., whose maternal viral load ≥ 1000 cp/mL at EPI-2 or M6) received an extended postnatal prophylaxis (PNP) with lamivudine until end of follow-up or the end of breastfeeding. RESULTS: Between 4 December 2019 and 4 December 2020, 118 mothers living with HIV-1 were identified, and 102 eligible mother/infant pairs had their infants tested for HIV EID. Six infants were newly diagnosed with HIV, and 96 HEU infants were followed-up for 10 months. Among the participants followed-up, all mothers were prescribed antiretrovirals. All 18 infants eligible for PNP at either EPI-2 or 6 months (M6) were initiated on lamivudine. No HIV transmission occurred, and no serious adverse events were reported in infants receiving lamivudine. CONCLUSIONS: The PREVENIR-PEV prevention package integrated into existing care is safe and its implementation is feasible in a LMIC with a low HIV prevalence. More research is needed to target mother/infant pairs not adhering to the intervention proposed in this trial. TRIAL REGISTRATION: NCT03869944; first registered on 11/03/2019.

Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.

Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta-analysis.

INTRODUCTION: Among many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta-analysis evaluates the relationship between tenofovir alafenamide use and lipid-profile alterations in people living with HIV. METHODS: We searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated. RESULTS: Sixty-five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low-density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low-density lipoprotein cholesterol (-9.31 mg/dl) and total cholesterol (-8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92-1.84), which became more pronounced over time. Meta-regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide. CONCLUSIONS: Tenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.

Oral HIV pre-exposure prophylaxis use and resistance-associated mutations among men who have sex with men and transgender persons newly diagnosed with HIV in the Netherlands: results from the ATHENA cohort, 2018 to 2022.

BackgroundIn the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known.AimWe assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands.MethodsData on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree.ResultsData on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs.ConclusionThe prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.

A randomised control trial of BIC/F/TAF vs DRV/c/F/TAF in context of HIV test-and-treat, BicTnT.

BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.

Switching to Low Neurotoxic Antiretrovirals to Improve Neurocognition Among People Living With HIV-1-Associated Neurocognitive Disorder: The MARAND-X Randomized Clinical Trial.

BACKGROUND: The pathogenesis of HIV-associated neurocognitive (NC) impairment is multifactorial, and antiretroviral (ARV) neurotoxicity may contribute. However, interventional pharmacological studies are limited. METHODS: Single-blind, randomized (1:1), controlled trial to assess the change of NC performance (Global Deficit Score, GDS, and domain scores) in PLWH with NC impairment randomized to continue their standard of care treatment or to switch to a less neurotoxic ARV regimen: darunavir/cobicistat, maraviroc, emtricitabine (MARAND-X). Participants had plasma and cerebrospinal fluid HIV RNA< 50 copies/mL, R5-tropic HIV, and were on ARV regimens that did not include efavirenz and darunavir. The change of resting-state electroencephalography was also evaluated. The outcomes were assessed at week 24 of the intervention through tests for longitudinal paired data and mixed-effect models. RESULTS: Thirty-eight participants were enrolled and 28 completed the follow-up. Global Deficit Score improved over time but with no difference between arms in longitudinal adjusted models. Perceptual functions improved in the MARAND-X, while long-term memory improved only in participants within the MARAND-X for whom the central nervous system penetration-effectiveness (CNS penetration effectiveness) score increased by ≥3. No significant changes in resting-state electroencephalography were observed. CONCLUSIONS: In this small but well-controlled study, the use of less neurotoxic ARV showed no major beneficial effect over an unchanged regimen. The beneficial effects on the memory domain of increasing CNS penetration effectiveness score suggest that ARV neuropenetration may have a role in cognitive function.

Induced abortion incidence and associated factors in a cohort of women living with HIV in Rio De Janeiro, Brazil, 1996-2016.

BACKGROUND: Abortion is a public health problem in Latin America and is more common among women living with HIV. OBJECTIVE: to verify the incidence and factors associated with induced abortion in a cohort of women living with HIV assisted in a reference service for care for individuals with HIV/AIDS in Rio de Janeiro/Brazil. METHODS: Prospective cohort during the period 1996-2016. We estimated the incidence of induced abortions during follow-up in the cohort by calculating person-time incidence rates [per 100 persons-years (PY)] and investigated the factors associated with the outcome "induced abortion" using a generalized linear mixed model. RESULTS: 753 women and 210 pregnancies were included in the present analysis. We estimated an induced abortion incidence rate of 0.68/100 persons-years (95% confidence interval [CI]: 0.47; 0.94) in the study period, with a significant reduction after 2006. The main factors associated with an induced abortion were currently living with a partner (adjusted OR [AdjOR] 0.32 95% CI: 0.10-0.98), number of children (2 children AdjOR 0.12, 95% CI: 0.02-0.95) and the type of antiretroviral treatment used (regimen without Efavirenz: AdjOR: 0.11, 95% CI 0.02-0.70). CONCLUSIONS: We showed a significant reduction in the incidence of induced abortions in a cohort of women living with HIV in Rio de Janeiro, Brazil, probably due to a decrease in the incidence of pregnancies observed in the same period. The factors associated with a lower occurrence of induced abortion suggest a good integration between the clinical and reproductive assistance offered to those women.