[Temporal evolution of antiretroviral therapy (2017-2021): analysis of treatment change and its economic impact]. / Evolución temporal de la terapia antirretroviral (2017-2021): análisis de la modificación del tratamiento y su impacto económico.

OBJECTIVE: To analyze the modifications of antiretroviral therapy (ART) and their economic impact on daily clinical practice. METHODS: Observational, retrospective study of patients who started ART between 01/2017-12/2021 (follow-up until 12/2022). Variables collected: prescribed ART, duration, the reason for the change, and treatment costs. RESULTS: A total of 280 patients initiated ART therapy. The median durability of 1st line was: 19.9 months in 2017 (95%CI 13.9-25.9), 12.2 months in 2018 (95%CI 4.7-19.7), 27.4 months in 2019 (95%CI 6.8-48.1) and the median was not reached for the years 2020 and 2021 (p<0.001). Triple therapy with protease inhibitors was changed in 63.8% (81/127) of cases, followed by integrase inhibitors 52.1% (159/305), while dual therapy (DTG/3TC) only in 8.3% (7/84). The main cause of discontinuation was simplification/optimization 47.5% (124/261), followed by adverse effects 21.8% (57/261), with 2017 being the only year where simplification/optimization was at the same level as adverse effects. The economic impact of ART changes resulted in an average cost reduction of 34.0€ [-391.4 to +431.4] per month per patient. The year 2019 stands out as the only year where these changes were associated with an increase in mean additional cost (23.4€ [-358.3 to +431.4]). CONCLUSIONS: Optimization/simplification accounts for almost half of the reasons for TAR change, with an economic impact that, despite the inflection point of 2019, each year manages to exceed the previous one, achieving a progressive cost reduction maintained over time.

Economic evaluation of doravirine/tenofovir disoproxil fumarate/lamivudine for HIV-1-infected adults in Russia: a cost-minimization and budget impact analysis.

BACKGROUND: In Russia, before 2022, the list of vital and essential drugs for HIV-infected patients previously untreated with antiretroviral drugs included the fixed-dose combination rilpivirine/tenofovir disoproxil fumarate/emtricitabine (RPV/TDF/FTC) but not doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/TDF/3TC). METHODS: An indirect comparison of the efficacy of DOR/TDF/3TC and RPV/TDF/FTC defined by virologic suppression (HIV-1 RNA of <50 copies/mL at week 48) was made. The per-patient drug costs over 1 year were compared in a cost-minimization analysis. A budget impact analysis considered the costs to the healthcare system of including DOR/TDF/3TC as a treatment option for eligible patients in Russia over a 3-year time horizon. RESULTS: The indirect treatment comparison of DOR/TDF/3TC and RPV/TDF/FTC in treatment-naïve patients with baseline HIV-1 RNA 100,000 copies/ml or less showed no statistically significant difference (RR 0.914, 95% CI 0.833-1.003). In the cost-minimization analysis, the per-patient cost of one year of treatment with RPV/TDF/FTC and DOR/TDF/3TC was, respectively, ₽320,975 and ₽151,192, for a saving of ₽169,783. In the budget impact analysis, the adoption of DOR/TDF/3TC into clinical practice is expected to reduce drug costs by ₽333 million (23.8%) in year 3. CONCLUSIONS: Fixed-dose combination DOR/TDF/3TC is equally effective and cost-saving compared to RPV/TDF/FTC from Russian vital and essential drugs list perspective.

The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies-A perspective from US Medicaid data.

BACKGROUND: People with human immunodeficiency virus (HIV)-1 face challenges with treatment adherence for various reasons, including consideration of neuropsychiatric disorders and neuropsychiatric adverse reactions associated with antiretroviral therapy (ART). METHODS: A retrospective cohort study was conducted using administrative claims data from the IBM MarketScan® Multi-State Medicaid Database (1/1/2014-12/31/2017). Adults (≥18 years) diagnosed with HIV-1 and newly initiated on antiretroviral therapy with continuous health plan enrollment were included. Primary outcome was the 6-month period prevalence of neuropsychiatric events (NPEs) of interest after ART initiation. RESULTS: Among 1971 newly treated patients included in the study, mean age (standard deviation [SD]) was 38.5 (12.7) years, and 41.4% were female. During the 6 months after ART initiation, 51.4% of patients had a claim for ≥1 NPE versus 30.3% of matched patients without HIV. Among newly treated patients, the most common (≥10%) NPE claims were for depression (42.2%), anxiety (15.8%), headache (11.9%), and bipolar/manic depression (10.1%). Also in this group, the mean (SD) total all-cause healthcare cost during the 6-month post-ART initiation was $16,632 ($33,928), of which $2914 ($18,233) was NPE-related. CONCLUSIONS: In summary, in this Medicaid study of people newly initiated on ART, there was a high prevalence of NPEs, and incremental NPE-associated costs were considerable.

Ethical issues in establishing the efficacy and safety of long-acting injectable pre-exposure prophylaxis for HIV prevention: the HPTN 083 trial.

Two multinational clinical trials have shown safety and efficacy of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis (PrEP). These results will alter the landscape of HIV prevention and related research. Nevertheless, designing and conducting this research involved several ethical issues. This Viewpoint describes how we managed ethical issues over the duration of one of these trials (HPTN 083). Specifically, we discuss the rationale for pursuing a long-acting injectable agent in the presence of effective oral PrEP, trial design choices, site selection and local standards of prevention, data monitoring and early stopping, effects of the COVID-19 pandemic, post-trial access, and assessment of long-term safety.

Assessment of the impact of HIV infection and anti-retroviral treatment on the cardiometabolic health of pregnant mothers and their offspring (ARTMOMSBABES).

BACKGROUND: The risk of cardiovascular diseases (CVDs) is becoming more prevalent in pregnant women though not much data is available for pregnant women with human immunodeficiency virus (HIV). Foetoplacental vascular endothelial dysfunction is thought to be at the origin of chronic diseases such as diabetes and obesity later on in life. Because HIV and anti-retroviral treatment (ARTs) are associated with endothelial dysfunction, children exposed in utero to these conditions may be at greater risk of developing CVDs. Despite the high prevalence of HIV in pregnant South African women, little is known about the effects of ART on the cardiovascular health of the mother and offspring. Hence, the proposed study intends to investigate how HIV/ARTs may affect the cardiovascular health of the mother and offspring at different time points during the pregnancy and up to 2 years after birth. METHODS: A longitudinal case-control study in HIV positive pregnant women on ART and HIV negative pregnant women will be conducted. All pregnant women will be assessed for cardio-metabolic risk factors and markers (lipids, anthropometric and glycaemic indies, oxidative stress), hemodynamic status (blood pressure parameters) and vascular function (arterial compliance, retinal microvasculature, uterine artery mean pulsatility index). Child health will be monitored in utero and postnatally via routine foetal health screening, placental integrity, anthropometry, blood pressure parameters, markers of oxidative stress and endothelial function in cord blood and cardiovascular epigenetic markers in urine. DISCUSSION: There is a paucity of studies in South Africa and sub-Sahara Africa as a whole that utilised a longitudinal study model to assess the effects of ARTs on vascular endothelial changes in pregnant women living with HIV and the cardiometabolic health of their offspring. This study will therefore help to monitor changes in cardiometabolic risk during pregnancy and in children exposed in utero to HIV-infection and ART use. Findings from this study will provide useful information for developing guidelines on the use of ARTs in pregnancy and management of cardiometabolic health of the offspring of HIV positive mothers.

[Effectiveness, safety, and economic impact of the bictegravir/emtricitabine/tenofovir alafenamide regimen in real clinical practice cohort of HIV-1 infected adult patients]. / Efectividad, seguridad e impacto económico del régimen de bictegravir/emtricitabina/tenofovir alafenamida en una cohorte de pacientes adultos infectados por VIH-1 en la práctica clínica real.

OBJECTIVE: Among the new antiretroviral treatment (ART) regimens, bictegravir (BIC) stands out, a recently incorporated integrase inhibitor. BIC conjugated with emtricitabine (FTC) and tenofovir alafenamide (TAF) has been shown to be non-inferior in efficacy as initiation therapy in a single daily dose regimen compared to other initiation ART. The objective of our study is to evaluate the impact of the inclusion of this new ART scheme in real clinical practice. METHODS: Observational, retrospective and descriptive study that included all adult HIV patients (age ≥18 years) who had been treated with BIC/FTC/TAF for at least 24 consecutive weeks for 1.5 year to evaluate effectiveness, safety and economic impact. RESULTS: A total of 115 patients were included. There were 28 patients without previous treatment, naive, (24.3%). The pretreated patients had a mean of 42±9 months of prior ART. The percentage of patients at week 24 after switching to BIC/FTC/TAF with suppressed plasma viral load was 88% in the naive group and 94.1% in the pretreated group. Adverse events were reported in 8 (7%) patients. The economic impact of the change to BIC/FTC/TAF for these patients was €1,202.63/patient/year, representing an increase of 9.3%. CONCLUSIONS: Our results correlate with the results of two phase 3 non-inferiority clinical trials in naive patients (88% and 84%) and those of a phase 3 non-inferiority clinical trial in pretreated patients (86%). However, we found a large difference between the high percentages of patients reporting an adverse event in three phase 3 clinical trials and our results.

Assessment of atherosclerotic cardiovascular disease risks between people living with HIV receiving first-line and second-line antiretroviral therapy in a resource-limited setting.

Cardiovascular disease has become an important health problem in people living with HIV (PLHIV) who receive antiretroviral therapy (ART). Atherosclerotic cardiovascular disease (ASCVD) risk score is a non-invasive tool to estimate the 10-year risk for ASCVD. A cross-sectional study was conducted among PLHIV receiving ART in a resource-limited setting, in order to assess the 10-year ASCVD risk between PLHIV receiving first-line and second-line ART. Of 460 participants with a mean age of 51.2 years, 262 (57.0%) were men. The mean duration of HIV infection was 14.7 years and the mean CD4 cell count was 509 cells/µL. Of all, 345 participants were receiving first-line ART and 115 were receiving second-line ART. The median 10-year ASCVD risk was 3.0% and 5.1% in the first-line and second-line ART groups, respectively (p = 0.029). The prevalence of a high 10-year ASCVD risk (≥20%) was significantly higher in the second-line ART group (3.5% vs 0.9%, p = 0.048). In multivariate analysis, receiving second-line ART was significantly associated with intermediate to high 10-year ASCVD risk (OR = 2.952; 95% CI, 1.656-6.997; p = 0.015). Atherosclerotic cardiovascular disease risk should be assessed in PLHIV, particularly those who receive second-line ART.

Vitamin D Assessment Over 48 Weeks in Treatment-Naive HIV Individuals Starting Lopinavir/Ritonavir Monotherapy.

BACKGROUND: Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status. OBJECTIVE: To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks. METHODS: Thirty-four treatment-naïve HIV individuals initiating lopinavir/ritonavir monotherapy and receiving clinical care from private practice in Houston, Texas, were included. Serum 25-hydroxyvitamin D levels from stored plasma samples collected from IMANI-2 pilot study at both baseline and 48 weeks were analyzed using LC-MS assays. Mean 25(OH)D at baseline and 48 weeks were compared using paired t-tests. Linear regression analysis was used to evaluate factors associated with changes in 25(OH)D. Logistic regression analyses were used to determine the effect of vitamin D status and covariates on CD4 cell count recovery. RESULTS: Mean 25(OH)D was significantly higher at 48 weeks (26.3 ng/mL (SD + 14.9); p=0.0003) compared to baseline (19.8 ng/mL (SD +12.1), with fewer individuals having vitamin D deficiency (41.2%) and severe deficiency (11.8%). Both body mass index and baseline CD4 cell count were significant independent covariates associated with 25(OH)D changes over 48 weeks. Baseline vitamin D status did not affect CD4 cell count recovery. However, in a 24-week multivariate analysis, current tobacco use was significantly associated with a decreased odds of CD4 cell count recovery (AOR 0.106, 95% CI 0.018-0.606; p=0.012). CONCLUSION: Individuals treated with lopinavir/ritonavir monotherapy had significantly higher 25(OH)D after 48 weeks. Current tobacco users had significantly diminished CD4 cell count recovery after starting treatment, warranting further clinical investigation.

The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women.

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir. METHODS: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. RESULTS: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. CONCLUSIONS: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.

"It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain.

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.

Effects of Antiretroviral Therapy on CD4+ Cell Count, HIV Viral Load and Death in a South African Cohort: A Modelling Study.

BACKGROUND AND OBJECTIVE: Combination antiretroviral therapy (cART) has improved the survival of HIV infected patients significantly. However, in some patients, survival is not guaranteed due to several factors that are either individual-based or cART based. This study presents an HIV, AIDS, Death (HAD) model to analyse the survival of patients on cART. MATERIALS AND METHODS: Continuous-time Markov models are fitted based on the states occupied for an HIV, AIDS and Death (HAD) model. These states are based on CD4 cell count. Factors that affect the survival of HIV-infected patients on cART are also analyzed. These, among others, include age, gender, routinely collected viral load, time on treatment, non-adherence and peripheral neuropathy. RESULTS: Patients with higher viral loads than expected are 11.1 times more likely to be at risk of HIV progression to the AIDS state and 1.1 times more likely to be at risk of mortality from a CD4 cell count state above 200 cell/mm3compared to patients with lower viral loads. Non-adherence to treatment increases the risk of transition from CD4 cell count state above 200 cell/mm3 to the AIDS state by 2.2 folds. Patients who were non-adherent to treatment are 3.8 times more likely to transit from the CD4 state above 200 cell/mm3 to death compared to patients who were adherent to treatment. Patients are expected to recover from the AIDS state after one year of treatment. CONCLUSIONS: Recovery from AIDS state by HIV infected patients on cART is likely to occur after one year of cART treatment. However, if the viral load remains higher than expected, this increases risks of immune deterioration even after having achieved normal CD4 cell counts and consequently, mortality risks are increased.

Adverse events in Chinese human immunodeficiency virus (HIV) patients receiving first line antiretroviral therapy.

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.

A discrete choice experiment to assess patients' preferences for HIV treatment in the rural population in Colombia.

Aim: To elicit patients' preferences for HIV treatment of the rural population in Colombia.Methods: A discrete choice experiment (DCE), conducted in a HIV clinic in Bogotá, was used to examine the trade-off between five HIV treatment attributes: effect on life expectancy, effect on physical activity, risk of moderate side-effects, accessibility to clinic, and economic costs to access controls. Attributes selection was based on literature review, expert consultation and a focus group with six patients. An efficient experimental design was used to define two versions of the questionnaire with each of 12 choice sets and a dominance task was added to check reliability. A mixed logit model was then used to analyse the data and sub-group analyses were conducted on the basis of age, gender, education, and sexual preference.Results: A total of 129 HIV patients were included for analysis. For all treatment attributes, significant differences between at least two levels were observed, meaning that all attributes were significant predictors of choice. Patients valued the effect on physical activity (conditional relative importance of 27.5%) and the effect on life expectancy (26.0%) the most. Sub-group analyses regard age and education showed significant differences: younger patients and high educated patients valued the effect on physical activity the most important, whereas older patients mostly valued the effect on life expectancy and low educated patients mostly valued the accessibility to clinic.Limitations: One potential limitation is selection bias, as only patients from one HIV clinic were reached. Additionally, questionnaires were partly administered in the waiting rooms, which potentially led to noise in the data.Conclusions: This study suggests that all HIV treatment characteristics included in this DCE were important and that HIV patients from rural Colombia valued short-term efficacy (i.e. effect on physical activity) and long-term efficacy (i.e. effect on life expectancy) the most.

A discrete choice experiment to assess patients' preferences for HIV treatment in the urban population in Colombia.

Aim: This study aimed to assess patients' preferences for HIV treatment in an urban Colombian population.Methods: A Discrete Choice Experiment (DCE) was conducted. Urban Colombian HIV patients were asked to repetitively choose between two hypothetical treatments that differ in regard to five attributes 'effect on life expectancy', 'effect on physical activity', 'risk of moderate side effects, 'accessibility to clinic' and 'economic cost to access controls'. Twelve choice sets were made using an efficient design. A Mixed Logit Panel Model was used for the analysis and subgroup analyses were performed according to age, gender, education level and sexual preference.Results: A total of 224 HIV patients were included. All attributes were significant, indicating that there were differences between at least two levels of each attribute. Patients preferred to be able to perform all physical activity without difficulty, to have large positive effects on life expectancy, to travel less than 2 h, to have lower risk of side-effects and to have subsidized travel costs. The attributes 'effect on physical activity' and 'effects on life expectancy' were deemed the most important. Sub-analyses showed that higher educated patients placed more importance on the large positive effects of HIV treatment, and a more negative preference for subsidized travel cost (5% level).Limitations: A potential limitation is selection bias as it is difficult to make a systematic urban/rural division of respondents. Additional, questionnaires were partly administered in the waiting rooms, which potentially led to some noise in the data.Conclusions: Findings suggests that short-term efficacy (i.e. effect on physical activity) and long-term efficacy (i.e. effect on life expectancy) are the most important treatment characteristics for HIV urban patients in Colombia. Preference data could provide relevant information for clinical and policy decision-making to optimize HIV care.

Reducing cardiovascular risk among people living with HIV: Rationale and design of the INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) randomized controlled trial.

Cardiovascular disease (CVD) is a major cause of morbidity among people living with HIV (PLWH). Statins can safely and effectively reduce CVD risk in PLWH, but evidence-based statin therapy is under-prescribed in PLWH. Developed using an implementation science framework, INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) is a stepped-wedge cluster randomized trial that addresses organization-, clinician- and patient-level barriers to statin uptake in Los Angeles community health clinics serving racially and ethnically diverse PLWH. After assessing knowledge about statins and barriers to clinician prescribing and patient uptake, we will design, implement and measure the effectiveness of (1) educational interventions targeting leadership, clinicians, and patients, followed by (2) behavioral economics-informed clinician feedback on statin uptake. In addition, we will assess implementation outcomes, including changes in clinician acceptability of statin prescribing for PLWH, clinician acceptability of the education and feedback interventions, and cost of implementation.

Prevention of cardiovascular disease among people living with HIV in sub-Saharan Africa.

As longevity has increased for people living with HIV (PLWH) in the United States and Europe, there has been a concomitant increase in the prevalence of cardiovascular disease (CVD) risk factors and morbidity in this population. Whereas the availability of HIV antiretroviral therapy has resulted in dramatic increases in life expectancy in sub-Saharan Africa (SSA), where over two thirds of PLWH reside, if and how these trends impact the epidemiology of CVD is less clear. In this review, we describe the current state of the science on how both HIV and its treatment impact CVD risk factors and outcomes among PLWH in sub-Saharan Africa, including regional factors (unique to SSA) likely to differentiate these relationships from the global North. We then outline how current regional guidelines address CVD prevention among PLWH and which clinical and structural interventions are best poised to confront the co-epidemics of HIV and CVD in the region. We conclude with a discussion of key research gaps that need to be addressed to optimally develop an actionable public health response.

Prevention of cardiovascular disease for historically marginalized racial and ethnic groups living with HIV: A narrative review of the literature.

Despite developments to improve health in the United States, racial and ethnic disparities persist. These disparities have profound impact on the wellbeing of historically marginalized racial and ethnic groups. This narrative review explores disparities by race in people living with cardiovascular disease (CVD) and the Human Immunodeficiency Virus (HIV). We discuss selected common social determinants of health for both of these conditions which include; regional historical policies, incarceration, and neighborhood effects. Data on racial disparities for persons living with comorbid HIV and CVD are lacking. We found few published articles (n = 7) describing racial disparities for persons living with both comorbid HIV and CVD. Efforts to reduce CVD morbidity in historically marginalized racial and ethnic groups with HIV must address participation in clinical research, social determinants of health and translation of research into clinical practice.

Effectiveness, Safety, and Costs of Dolutegravir/Abacavir/Lamivudine Single-Tablet Regimen in a Real-Life Cohort of HIV-1 Adult Infected Patients.

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.

Impact of immediate initiation of antiretroviral therapy on HIV patient satisfaction.

OBJECTIVES: Immediate ART (or early access to ART for all, EAAA) is becoming a national policy in many countries in sub-Saharan Africa. It is plausible that the switch from delayed to immediate ART could either increase or decrease patient satisfaction with treatment. A decrease in patient satisfaction would likely have detrimental consequences for long-term retention and adherence, in addition to the value lost because of the worsening patient experience itself. We conducted a pragmatic stepped-wedge cluster-randomized controlled trial (SW-cRCT) to determine the causal impact of immediate treatment for HIV on patient satisfaction. DESIGN: This seven-step SW-cRCT took place in 14 public-sector health facilities in Eswatini's Hhohho region, from September 2014 to August 2017. METHODS: During each step of the trial, we randomly selected days for data collection at each study facility. During these days, a random sample of HIV patients were selected for outcome assessment. In total, 2629 patients provided data on their overall patient satisfaction and satisfaction with the following four domains of the patient experience using a five-point Likert scale: wait time, consultation time, involvement in treatment decisions, and respectful treatment. Higher values on the Likert scale indicated lower patient satisfaction. We analyzed the data using a multilevel ordered logistic regression model with individuals at the first level and health facilities at the second (cluster) level. RESULTS: The proportional odds ratio (OR) comparing EAAA to control was 0.91 (95% CI 0.66-1.25) for overall patient satisfaction. For the specific domains of the patient experience, the ORs describing the impact of EAAA on satisfaction were 1.04 (95% CI 0.61-1.78) for wait time, 0.90 (95% CI 0.62-1.31) for involvement in treatment decisions, 0.86 (95% CI 0.61-1.20) for consultation time, and 1.35 (95% CI 0.93-1.96) for respectful treatment. These results were robust across a wide range of sensitivity analyses. Over time - and independent of EAAA - we observed a worsening trend for both overall patient satisfaction and satisfaction in the four domains of the patient experience we measured. CONCLUSION: Our findings support the policy change from delayed to immediate ART in sub-Saharan Africa. Immediate (versus delayed) ART in public-sector health facilities in Eswatini had no effect on either overall patient satisfaction or satisfaction with four specific domains of the patient experience. At the same time, we observed a strong secular trend of decreasing patient satisfaction in both the intervention and the control arm of the trial. Further implementation research should identify approaches to ensure high patient satisfaction as ART programs grow and mature.

Liver Fibrosis Assessment in a Cohort of Greek HIV Mono-Infected Patients by Non-Invasive Biomarkers.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) is common in HIV-infected individuals. Liver biopsy remains the gold-standard procedure for the diagnosis of liver fibrosis, but both Transient Elastography (TE) and Non-invasive Biomarkers (NIBMs) have emerged as alternatives. OBJECTIVES: Our study's aim was to validate commonly used NIBMs for the assessment of liver fibrosis in a cohort of Greek HIV-mono-infected patients. METHODS: Inclusion criteria were confirmed HIV-infection and age>18 years and exclusion criteria HBV or HCV seropositivity, liver disease other than NAFLD, alcohol abuse, ascites, transaminases levels>4xULN(upper limit of normal) and Body-Mass index(BMI)>40. Liver stiffness (LS) measurement with TE and thorough laboratory work up and medical history were acquired at study entry. FIB-4, APRI, NFS, BARD, Forns and Lok scores were calculated for each patient. RESULTS: A total of 157 patients were eligible for this study. Significant liver fibrosis, compatible with Metavir score of F3-F4, was found in only 11(7%) patients. These findings were in accordance with those of the NIBMs; the BARD score constituting the only exception, allocating 102(65%) patients as having significant liver fibrosis. In order to obtain a balance between sensitivity and specificity new cut-offs for each NIBM were calculated; FIB-4 score yielded the best results, since by changing the cut-off to 1.49 a sensitivity and specificity balanced for both close to 85% was achieved. CONCLUSION: Our findings suggest that NIBMs can be used for the evaluation of liver fibrosis in HIV mono-infected patients. New cut-offs for NIBMs should probably be calculated, to help distinguishing patients with significant from those with mild/no fibrosis.