Does type of antiretroviral therapy pick-up point influence 12-month virologic suppression in South Africa?

We assessed the impact of community- versus clinic-based medication pick-up on rates of virologic suppression in an observational cohort of adults on ART enrolled in a decentralized antiretroviral therapy program (CCMDD) in South Africa. Participants either attended clinics where they were given the choice to pick up ART in community venues or traditional clinics, or clinics where this pathway was assigned. Among 1856 participants, 977 (53%) opted for community ART pick-up at enrollment, and 1201 (86%) were virologically suppressed at one year. Because of missing data on virologic suppression, primary results are based on a model incorporating multiple imputation. In addition to age and gender, distance from clinic and year of HIV diagnosis were included in the multivariable model. There was no difference in opting for clinic- vs. community-based pick-up with regard to achieving 12-month virologic suppression (aRR 1.02, 95% CI 0.98-1.05) in clinics offering choice. There was no impact of assigning all participants to an external pick-up point (aRR 1.00, 95% CI 0.95-1.06), but virologic suppression was reduced in the clinic that assigned participants to clinic pick-up (aRR 0.87, 95% CI 0.81-0.92). These results suggest that provision of community-based ART has not reduced continued virologic suppression in the population enrolled in the CCMDD program.

A Brief Mind-body Intervention Is Feasible and May Prevent Persistent Pain After Acute Orthopaedic Traumas: A Randomized Controlled Trial.

BACKGROUND: Approximately 20% to 50% of patients develop persistent pain after traumatic orthopaedic injuries. Psychosocial factors are an important predictor of persistent pain; however, there are no evidence-based, mind-body interventions to prevent persistent pain for this patient population. QUESTIONS/PURPOSES: (1) Does the Toolkit for Optimal Recovery after Injury (TOR) achieve a priori feasibility benchmarks in a multisite randomized control trial (RCT)? (2) Does TOR demonstrate a preliminary effect in improving pain, as well as physical and emotional function? METHODS: This pilot RCT of TOR versus a minimally enhanced usual care comparison group (MEUC) was conducted among 195 adults with an acute orthopaedic traumatic injury at risk for persistent pain at four geographically diverse Level 1 trauma centers between October 2021 to August 2023. Fifty percent (97 of 195) of participants were randomized to TOR (mean age 43 ± 17 years; 67% [65 of 97] women) and 50% (98) to MEUC (mean age 45 ± 16 years; 67% [66 of 98] women). In TOR, 24% (23 of 97) of patients were lost to follow-up, whereas in the MEUC, 17% (17 of 98) were lost. At 4 weeks, 78% (76 of 97) of patients in TOR and 95% (93 of 98) in the MEUC completed the assessments; by 12 weeks, 76% (74 of 97) of patients in TOR and 83% (81 of 98) in the MEUC completed the assessments (all participants were still included in the analysis consistent with an intention-to-treat approach). The TOR has four weekly video-administered sessions that teach pain coping skills. The MEUC is an educational pamphlet. Both were delivered in addition to usual care. Primary outcomes were feasibility of recruitment (the percentage of patients who met study criteria and enrolled) and data collection, appropriateness of treatment (the percent of participants in TOR who score above the midpoint on the Credibility and Expectancy Scale), acceptability (the percentage of patients in TOR who attend at least three of four sessions), and treatment satisfaction (the percent of participants in TOR who score above the midpoint on the Client Satisfaction Scale). Secondary outcomes included additional feasibility (including collecting data on narcotics and rescue medications and adverse events), fidelity (whether the intervention was delivered as planned) and acceptability metrics (patients and staff), pain (numeric rating scale), physical function (Short Musculoskeletal Function Assessment questionnaire [SMFA], PROMIS), emotional function (PTSD [PTSD Checklist], depression [Center for Epidemiologic Study of Depression]), and intervention targets (pain catastrophizing, pain anxiety, coping, and mindfulness). Assessments occurred at baseline, 4 and 12 weeks. RESULTS: Several outcomes exceeded a priori benchmarks: feasibility of recruitment (89% [210 of 235] of eligible participants consented), appropriateness (TOR: 73% [66 of 90] scored > midpoint on the Credibility and Expectancy Scale), data collection (79% [154 of 195] completed all surveys), satisfaction (TOR: 99% [75 of 76] > midpoint on the Client Satisfaction Scale), and acceptability (TOR: 73% [71 of 97] attended all four sessions). Participation in TOR, compared with the MEUC, was associated with improvement from baseline to postintervention and from baseline to follow-up in physical function (SMFA, baseline to post: -7 [95% CI -11 to -4]; p < 0.001; baseline to follow-up: -6 [95% CI -11 to -1]; p = 0.02), PROMIS (PROMIS-PF, baseline to follow-up: 2 [95% CI 0 to 4]; p = 0.045), pain at rest (baseline to post: -1.2 [95% CI -1.7 to -0.6]; p < 0.001; baseline to follow-up: -1 [95% CI -1.7 to -0.3]; p = 0.003), activity (baseline to post: -0.7 [95% CI -1.3 to -0.1]; p = 0.03; baseline to follow-up: -0.8 [95% CI -1.6 to -0.1]; p = 0.04), depressive symptoms (baseline to post: -6 [95% CI -9 to -3]; p < 0.001; baseline to follow-up: -5 [95% CI -9 to -2]; p < 0.002), and posttraumatic symptoms (baseline to post: -4 [95% CI -7 to 0]; p = 0.03; baseline to follow-up: -5 [95% CI -9 to -1]; p = 0.01). Improvements were generally clinically important and sustained or continued through the 3 months of follow-up (that is, above the minimum clinically important different [MCID] of 7 for the SMFA, the MCID of 3.6 for PROMIS, the MCID of 2 for pain at rest and pain during activity, the MCID of more than 10% change in depressive symptoms, and the MCID of 10 for posttraumatic symptoms). There were treatment-dependent improvements in pain catastrophizing, pain anxiety, coping, and mindfulness. CONCLUSION: TOR was feasible and potentially efficacious in preventing persistent pain among patients with an acute orthopaedic traumatic injury. Using TOR in clinical practice may prevent persistent pain after orthopaedic traumatic injury. LEVEL OF EVIDENCE: Level I, therapeutic study.

Diet, physical activity, and obesity among ART-experienced people with HIV in South Africa.

The prevalence of non-communicable diseases (NCDs) is increasing in South Africa, in part due to poor nutrition, physical inactivity, and obesity. We characterized the habits and understanding of diet, exercise, and obesity among people with HIV (PWH) taking antiretroviral therapy (ART). We conducted a cross-sectional study of ART-experienced PWH attending an HIV community health center near Cape Town, South Africa. We included PWH currently prescribed ART, older than 21y, and not pregnant. We collected demographic and clinical information and interviewed participants regarding their behaviors and knowledge related to diet, physical activity, and obesity. From March 2015 - February 2016, we enrolled 458 participants. Self-reported diets were low in nutritional diversity: 202 reported eating only starch and protein without vegetable/fruit in the prior 24 h. Although most participants (96%) acknowledged that exercise had health benefits, only 215 participants engaged in daily 30-minute walking or exercise. One quarter of participants recognized nocontributors to obesity, and almost 20% identified no health problems associated with obesity. Participants had diets low in nutritional diversity, modest exercise habits, and limited understanding of the impact of obesity on health. Further understanding of barriers to improving diet and exercise and reducing obesity are essential, especially as PWH age.

Geographic variation in 5-year mortality following HIV diagnosis: implications for clinical interventions.

Characterizing spatial distribution of HIV outcomes is vital for targeting interventions to areas most at risk. We performed spatial analysis to identify geographic clusters and factors associated with mortality in KwaZulu-Natal, South Africa. We utilized Sizanani trial (NCT01188941) data, which enrolled participants August 2010-January 2013 and obtained vital status at 5.8 (IQR 5.0-6.4) years of follow-up. We mapped geocoded addresses to 2011 Census-defined small area layer (SAL) centroids, used Kulldorff's spatial scan statistic to identify mortality clusters, and compared socio-demographic factors for SALs within and outside mortality clusters. We assigned 1,143 participants living with HIV (260 [23%] of whom died during follow-up) to 677 SALs. One lower mortality cluster (n = 90, RR = 0.23, p = 0.022) was identified near a hospital outside Durban. SALs in the cluster were younger (24y vs 25y, p < 0.001); had fewer bedrooms/household (3 vs 4, p < 0.001); had more females (52% vs 51%, p = 0.013) and residents with no schooling past age 20 (4% vs 3%, p < 0.001) or no education at all (4% vs 3%, p < 0.001); had fewer residents with income >3,200 ZAR/month (5% vs 9%, p < 0.001); and had reduced access to piped water (p < 0.001), refuse disposal (p < 0.001), and toilets (p < 0.001). Targeted interventions may improve outcomes in areas with similar characteristics.

The relationship between mindfulness and enduring somatic threat severity in long-term cardiac arrest survivors.

BACKGROUND: Cardiac arrest (CA) survivors experience continuous exposures to potential traumas though chronic cognitive, physical and emotional sequelae and enduring somatic threats (ESTs) (i.e., recurring somatic traumatic reminders of the event). Sources of ESTs can include the daily sensation of an implantable cardioverter defibrillator (ICD), ICD-delivered shocks, pain from rescue compressions, fatigue, weakness, and changes in physical function. Mindfulness, defined as non-judgmental present-moment awareness, is a teachable skill that might help CA survivors cope with ESTs. Here we describe the severity of ESTs in a sample of long-term CA survivors and explore the cross-sectional relationship between mindfulness and severity of ESTs. METHODS: We analyzed survey data of long-term CA survivors who were members of the Sudden Cardiac Arrest Foundation (collected 10-11/2020). We assessed ESTs using 4 cardiac threat items from the Anxiety Sensitivity Index-revised (items range from 0 "very little" to 4 "very much") which we summed to create a score reflecting total EST burden (range 0-16). We assessed mindfulness using the Cognitive and Affective Mindfulness Scale-Revised. First, we summarized the distribution of EST scores. Second, we used linear regression to describe the relationship between mindfulness and EST severity adjusting for age, gender, time since arrest, COVID-19-related stress, and loss of income due to COVID. RESULTS: We included 145 CA survivors (mean age: 51 years, 52% male, 93.8% white, mean time since arrest: 6 years, 24.1% scored in the upper quarter of EST severity). Greater mindfulness (ß: -30, p = 0.002), older age (ß: -0.30, p = 0.01) and longer time since CA (ß: -0.23, p = 0.005) were associated with lower EST severity. Male sex was also associated with greater EST severity (ß: 0.21, p = 0.009). CONCLUSION: ESTs are common among CA survivors. Mindfulness may be a protective skill that CA survivors use to cope with ESTs. Future psychosocial interventions for the CA population should consider using mindfulness as a core skill to reduce ESTs.

Experiences of participants in a decentralized antiretroviral therapy program in South Africa during the COVID-19 pandemic.

The COVID-19 pandemic and associated restrictions could adversely affect long-term HIV care. We evaluated the experiences of people receiving antiretroviral therapy (ART) through a decentralized delivery program in South Africa during the COVID-19 pandemic. We telephoned a random subsample of participants enrolled in a prospective cohort study in KwaZulu-Natal in April and May 2020 and administered a semi-structured telephone interview to consenting participants. We completed interviews with 303 of 638 contacted participants (47%); 66% were female, with median age 36y. The most common concerns regarding the COVID-19 pandemic were food running out (121, 40%), fear of becoming infected with COVID-19 (103, 34%), and being unable to work/losing employment or income (102, 34%). Twenty-five (8%) participants had delayed ART pick-up due to the pandemic, while 212 (70%) had new concerns about ART access going forward. Mental health scores were worse during the pandemic compared to baseline (median score 65.0 vs 80.0, p < 0.001). Decentralized ART distribution systems have the potential to support patients outside of health facilities during the COVID-19 pandemic, but economic concerns and mental health impacts related to the pandemic must also be recognized and addressed.

Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community.

BACKGROUND: People living with HIV (PLWH) may have a poorer prognosis with COVID-19 infection and are an important population for COVID-19 vaccination. We assessed the willingness and reasons for COVID-19 vaccine acceptance or hesitancy among PLWH in South Africa. METHODS: We conducted a cross-sectional study consisting of telephone interviews with a randomly selected subset of participants enrolled in a prospective observational cohort study evaluating a decentralized antiretroviral therapy (ART) delivery program in South Africa. Questions assessed willingness to accept a future COVID-19 vaccine, concerns regarding COVID-19 vaccination, and overall vaccine confidence. Interviews were conducted between September 2020 and January 2021. We evaluated participant demographics, sources of COVID-19 information, stigma and medical mistrust, uptake of non-pharmaceutical interventions, and socioeconomic impacts of the COVID-19 pandemic as potential covariates of willingness to accept vaccination. RESULTS: We completed interviews with 213 participants; 153 (72%) were female, median age 35y, and 100 (47%) had completed secondary school. Among the participants, 121 (57%) were willing to accept future vaccination, 46 (22%) were unsure, and 45 (21%) stated they did not intend to be vaccinated. Fear of side effects, reported by 42 (20%), was the most common concern about COVID-19 vaccination. Older age was associated with willingness to accept vaccination (aOR 1.75 for every 10-year increase in age, 95% CI 1.10-2.78, p = 0.02), while higher medical mistrust related to COVID-19 (aOR 0.21, 95% CI 0.093-0.45, p < 0.001) and use of social media for COVID-19 information (aOR 0.30, 95% CI 0.11-0.84, p = 0.02) were associated with lower willingness to accept vaccination. CONCLUSIONS: In this cohort of PLWH in South Africa, over half were willing to accept COVID-19 vaccination, although a substantial proportion remained unsure or were not willing to be vaccinated. Public health messaging should emphasize the safety and efficacy of COVID-19 vaccination and address misinformation and medical mistrust among PLWH. Ongoing efforts to ensure access to COVID-19 vaccines for vulnerable populations are crucial.

Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy.

BACKGROUND: The prevalence and mortality risk of depression in people with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) is higher than in the general population, yet biomarkers for therapeutic targeting are unknown. In the current study, we aimed to identify plasma metabolites associated with depressive symptoms in people with HIV receiving ART. METHODS: This is a prospective study of ART-treated HIV-infected adults with or without depressive symptoms assessed using longitudinal Beck Depression Inventory scores. Plasma metabolite profiling was performed in 2 independent cohorts (total n = 99) using liquid and gas chromatography and tandem mass spectrometry. RESULTS: Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate [DHEA-S], androstenediols, and pregnenolone sulfate) compared with those without depressive symptoms. The cortisol/DHEA-S ratio, an indicator of hypothalamic-pituitary-adrenal axis imbalance, was associated with depressive symptoms (P < .01) because of low DHEA-S levels, whereas cortisol was similar between groups. The odds of having depressive symptoms increased with higher cortisol/DHEA-S ratios (adjusted odds ratio, 2.5 per 1-unit increase in z score; 95% confidence interval, 1.3-4.7), independent of age and sex. The kynurenine-to-tryptophan ratio showed no significant associations. CONCLUSIONS: These findings suggest that altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression in ART-treated HIV-infected adults, representing a potential biological pathway for therapeutic targeting.

Medical Mistrust and Stigma Associated with COVID-19 Among People Living with HIV in South Africa.

We evaluated COVID-19 stigma and medical mistrust among people living with HIV in South Africa. We conducted telephone interviews with participants in a prospective study of a decentralized antiretroviral therapy program. Scales assessing medical mistrust, conspiracy beliefs, anticipated and internalized stigma, and stereotypes specific to COVID-19 were adapted primarily from the HIV literature, with higher scores indicating more stigma or mistrust. Among 303 participants, the median stigma summary score was 4 [interquartile range (IQR) 0-8; possible range 0-24] and 6 (IQR 2-9) for mistrust (possible range 0-28). A substantial proportion of participants agreed or strongly agreed with at least one item assessing stigma (54%) or mistrust (43%). Higher COVID-19 stigma was associated with female gender and antecedent HIV stigma, and lower stigma with reporting television as a source of information on COVID-19. Further efforts should focus on effects of stigma and mistrust on protective health behaviors and vaccine hesitancy.

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.

Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa.

Primary Care Providers' Perceived Barriers and Needs for Support in Caring for Children with Autism.

A mixed methods approach was used to examine perspectives of 114 primary care providers regarding barriers and needs for support in caring for children with autism. The most common barriers related to lack of knowledge and resources for diagnosing and treating children with autism, and inadequate visit time and reimbursement.

Individualized PEEP to optimise respiratory mechanics during abdominal surgery: a pilot randomised controlled trial.

BACKGROUND: Higher intraoperative driving pressures (ΔP) are associated with increased postoperative pulmonary complications (PPC). We hypothesised that dynamic adjustment of PEEP throughout abdominal surgery reduces ΔP, maintains positive end-expiratory transpulmonary pressures (Ptp_ee) and increases respiratory system static compliance (Crs) with PEEP levels that are variable between and within patients. METHODS: In a prospective multicentre pilot study, adults at moderate/high risk for PPC undergoing elective abdominal surgery were randomised to one of three ventilation protocols: (1) PEEP≤2 cm H2O, compared with periodic recruitment manoeuvres followed by individualised PEEP to either optimise respiratory system compliance (PEEPmaxCrs) or maintain positive end-expiratory transpulmonary pressure (PEEPPtp_ee). The composite primary outcome included intraoperative ΔP, Ptp_ee, Crs, and PEEP values (median (interquartile range) and coefficients of variation [CVPEEP]). RESULTS: Thirty-seven patients (48.6% female; age range: 47-73 yr) were assigned to control (PEEP≤2 cm H2O; n=13), PEEPmaxCrs (n=16), or PEEPPtp_ee (n=8) groups. The PEEPPtp_ee intervention could not be delivered in two patients. Subjects assigned to PEEPmaxCrs had lower ΔP (median8 cm H2O [7-10]), compared with the control group (12 cm H2O [10-15]; P=0.006). PEEPmaxCrs was also associated with higher Ptp_ee (2.0 cm H2O [-0.7 to 4.5] vs controls: -8.3 cm H2O [-13.0 to -4.0]; P≤0.001) and higher Crs (47.7 ml cm H2O [43.2-68.8] vs controls: 39.0 ml cm H2O [32.9-43.4]; P=0.009). Individualised PEEP (PEEPmaxCrs and PEEPPtp_ee combined) varied widely (median: 10 cm H2O [8-15]; CVPEEP=0.24 [0.14-0.35]), both between, and within, subjects throughout surgery. CONCLUSIONS: This pilot study suggests that individualised PEEP management strategies applied during abdominal surgery reduce driving pressure, maintain positive Ptp_ee and increase static compliance. The wide range of PEEP observed suggests that an individualised approach is required to optimise respiratory mechanics during abdominal surgery. CLINICAL TRIAL REGISTRATION: NCT02671721.

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa.

BACKGROUND: Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa. METHODS: We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health). RESULTS: Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05-1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89-0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79-9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86-1.48) at age 60. CONCLUSIONS: Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.

Voluntary Community Human Immunodeficiency Virus Testing, Linkage, and Retention in Care Interventions in Kenya: Modeling the Clinical Impact and Cost-effectiveness.

Background: In southwest Kenya, the prevalence of human immunodeficiency virus (HIV) infection is about 25%. Médecins Sans Frontières has implemented a voluntary community testing (VCT) program, with linkage to care and retention interventions, to achieve the Joint United Nations Program on HIV and AIDS (UNAIDS) 90-90-90 targets by 2017. We assessed the effectiveness and cost-effectiveness of these interventions. Methods: We developed a time-discrete, dynamic microsimulation model to project HIV incidence over time in the adult population in Kenya. We modeled 4 strategies: VCT, VCT-plus-linkage to care, a retention intervention, and all 3 interventions combined. Effectiveness outcomes included HIV incidence, years of life saved (YLS), cost (2014 €), and cost-effectiveness. We performed sensitivity analyses on key model parameters. Results: With current care, the projected HIV incidence for 2032 was 1.51/100 person-years (PY); the retention and combined interventions decreased incidence to 1.03/100 PY and 0.75/100 PY, respectively. For 100000 individuals, the retention intervention had an incremental cost-effectiveness ratio (ICER) of €130/YLS compared with current care; the combined intervention incremental cost-effectiveness ratio was €370/YLS compared with the retention intervention. VCT and VCT-plus-linkage interventions cost more and saved fewer life-years than the retention and combined interventions. Baseline HIV prevalence had the greatest impact on the results. Conclusions: Interventions targeting VCT, linkage to care, and retention would decrease HIV incidence rate over 15 years in rural Kenya if planned targets are achieved. These interventions together would be more effective and cost-effective than targeting a single stage of the HIV care cascade.

Direct Comparison of the Precision of the New Hologic Horizon Model With the Old Discovery Model.

Previous publications suggested that the precision of the new Hologic Horizon densitometer might be better than that of the previous Discovery model, but these observations were confounded by not using the same participants and technologists on both densitometers. We sought to study this issue methodically by measuring in vivo precision in both densitometers using the same patients and technologists. Precision studies for the Horizon and Discovery models were done by acquiring spine, hip, and forearm bone mineral density twice on 30 participants. The set of 4 scans on each participant (2 on the Discovery, 2 on the Horizon) was acquired by the same technologist using the same scanning mode. The pairs of data were used to calculate the least significant change according to the International Society for Clinical Densitometry guidelines. The significance of the difference between least significant changes was assessed using a Wilcoxon signed-rank test of the difference between the mean square error of the absolute value of the differences between paired measurements on the Discovery (Δ-Discovery) and the mean square error of the absolute value of the differences between paired measurements on the Horizon (Δ-Horizon). At virtually all anatomic sites, there was a nonsignificant trend for the precision to be better for the Horizon than for the Discovery. As more vertebrae were excluded from analysis, the precision deteriorated on both densitometers. The precision between densitometers was almost identical when reporting only 1 vertebral body. (1) There was a nonsignificant trend for greater precision on the new Hologic Horizon compared with the older Discovery model. (2) The difference in precision of the spine bone mineral density between the Horizon and the Discovery models decreases as fewer vertebrae are included. (3) These findings are substantially similar to previously published results which had not controlled as well for confounding from using different subjects and technologists.

Impact of Medication Adherence on Virologic Failure in A5202: A Randomized, Partially Blinded, Phase 3B Study.

In AIDS Clinical Trials Group A5202, participants who reported missing their medication within the past month or not providing adherence reports at both 8 and 24 weeks had 5 times the hazard of virological failure compared to more adherent participants. Adherence interventions should focus on such patients.

Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection.

BACKGROUND: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. METHODS: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. RESULTS: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. CONCLUSIONS: Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives.

Impact of Cigarette Smoking and Smoking Cessation on Life Expectancy Among People With HIV: A US-Based Modeling Study.

BACKGROUND: In the United States, >40% of people infected with human immunodeficiency virus (HIV) smoke cigarettes. METHODS: We used a computer simulation of HIV disease and treatment to project the life expectancy of HIV-infected persons, based on smoking status. We used age- and sex-specific data on mortality, stratified by smoking status. The ratio of the non-AIDS-related mortality risk for current smokers versus that for never smokers was 2.8, and the ratio for former smokers versus never smokers was 1.0-1.8, depending on cessation age. Projected survival was based on smoking status, sex, and initial age. We also estimated the total potential life-years gained if a proportion of the approximately 248 000 HIV-infected US smokers quit smoking. RESULTS: Men and women entering HIV care at age 40 years (mean CD4+ T-cell count, 360 cells/µL) who continued to smoke lost 6.7 years and 6.3 years of life expectancy, respectively, compared with never smokers; those who quit smoking upon entering care regained 5.7 years and 4.6 years, respectively. Factors associated with greater benefits from smoking cessation included younger age, higher initial CD4+ T-cell count, and complete adherence to antiretroviral therapy. Smoking cessation by 10%-25% of HIV-infected smokers could save approximately 106 000-265 000 years of life. CONCLUSIONS: HIV-infected US smokers aged 40 years lose >6 years of life expectancy from smoking, possibly outweighing the loss from HIV infection itself. Smoking cessation should become a priority in HIV treatment programs.

Clinical Impact and Cost-effectiveness of Diagnosing HIV Infection During Early Infancy in South Africa: Test Timing and Frequency.

BACKGROUND: Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as "early infant HIV diagnosis" [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed. DESIGN/METHODS: We simulated 4 EID testing strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness; hereafter, "no EID"), testing once (at birth alone or at 6 weeks of age alone; hereafter, "birth alone" and "6 weeks alone," respectively), and testing twice (at birth and 6 weeks of age; hereafter "birth and 6 weeks"). We calculated incremental cost-effectiveness ratios (ICERs), using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants. RESULTS: In the base case (guideline-concordant care), the no EID strategy produced a life expectancy of 21.1 years (in the HIV-infected group) and 61.1 years (in the HIV-exposed group); lifetime cost averaged $1430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (26.5 years in the HIV-infected group and 61.4 years in the HIV-exposed group), costing $1840/infant tested. The ICER of the 6 weeks alone strategy versus the no EID strategy was $1250/year of life saved (19% of South Africa's per capita gross domestic product); the ICER for the birth and 6 weeks strategy versus the 6 weeks alone strategy was $2900/year of life saved (45% of South Africa's per capita gross domestic product). Increasing the proportion of caregivers who receive test results and the linkage of HIV-positive infants to antiretroviral therapy with the 6 weeks alone strategy improved survival more than adding a second test. CONCLUSIONS: EID at birth and 6 weeks improves outcomes and is cost-effective, compared with EID at 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs.

The Cost-effectiveness and Budget Impact of 2-Drug Dolutegravir-Lamivudine Regimens for the Treatment of HIV Infection in the United States.

BACKGROUND: Recommended human immunodeficiency virus (HIV) treatment regimens in the United States contain 3 antiretroviral agents, costing >$30 000/person/year. Pilot studies are evaluating the efficacy of dual therapy with dolutegravir (DTG) and lamivudine (3TC). We examined the potential cost-effectiveness and budget impact of DTG + 3TC regimens in the United States. METHODS: Using a mathematical model, we projected the clinical and economic outcomes of antiretroviral therapy (ART)-naive patients under 4 strategies: (1) no ART (for modeling comparison); (2) 2-drug: initial regimen of DTG + 3TC; (3) induction-maintenance: 48-week induction regimen of 3 drugs (DTG/abacavir [ABC]/3TC), followed by DTG + 3TC maintenance if virologically suppressed; and (4) standard of care: 3-drug regimen of DTG/ABC/3TC. Strategy-dependent model inputs, varied widely in sensitivity analyses, included 48-week virologic suppression (88%-93%), subsequent virologic failure (0.1%-0.6%/month), and Medicaid-discounted ART costs ($15 200-$39 600/year). A strategy was considered cost-effective if its incremental cost-effectiveness ratio (ICER) was <$100 000/quality-adjusted life-year (QALY). RESULTS: The 3 ART strategies had the same 5-year survival rates (90%). The ICER was $22 500/QALY for induction-maintenance and >$500 000/QALY for standard of care. Two-drug was the preferred strategy only when DTG + 3TC 48-week virologic suppression rate exceeded 90%. With 50% uptake of either induction-maintenance or 2-drug for ART-naive patients, cost savings totaled $550 million and $800 million, respectively, within 5 years; savings reached >$3 billion if 25% of currently suppressed patients were switched to DTG + 3TC maintenance. CONCLUSIONS: Should DTG + 3TC demonstrate high rates of virologic suppression, this regimen will be cost-effective and would save >$500 million in ART costs in the United States over 5 years.