Produce Prescriptions Sound Good, but Data to Support Them Are Lacking-That Could Soon Change.

This Medical News article discusses research initiatives to support produce prescriptions and other "food is medicine" nutrition programs in health care settings.

High frequency of memory stem cells with a distinct gene signature in HIV patients with treatment interruption.

Reservoirs of HIV remain a major obstacle to the complete eradication of virus despite regular anti-retroviral therapy (ART). Memory stem cells (Tscm), one of the major reservoirs, are relatively less studied owing to their presence in lower numbers and inaccessible anatomical locations. We have evaluated the molecular characteristics of Tscms in patients with ART interruption (n = 15) versus patients on uninterrupted ART (n = 12) using flow cytometry. RNA sequencing was done in the sorted Tscms to study the differential gene expression. Patients with ART interruption had significantly lower baseline CD4+T-cell counts and high viral loads as compared to patients on ART. The former group had significantly higher frequency of CD4+ and CD8+Tscms with a higher expression of PD-1 on CD8+Tscms. The transcriptome profile of Tscm was significantly different among the patient groups. The main pathways were cellular and metabolic pathways, cellular development pathways, cell differentiation and negative regulation of cellular migratory pathways. An increased yet dysfunctional CD8+ memory stem cells describe HIV-1-infected patients with break-in ART and a distinct transcriptional signature of CD4+ Tscm as compared to those of patients on ART. A more detailed understanding of the biology and dynamics of Tscm in future studies is warranted. Strategies to improve the functionality of the CD8+ Tscm will help these patients to tackle the outburst of viral replication that occurs after the cessation of therapy.

Anti-HIV Activity of Cucurbitacin-D against Cigarette Smoke Condensate-Induced HIV Replication in the U1 Macrophages.

Chemodietary agents are emerging as promising adjuvant therapies in treating various disease conditions. However, there are no adjuvant therapies available to minimize the neurotoxicity of currently existing antiretroviral drugs (ARVs). In this study, we investigated the anti-HIV effect of a chemodietary agent, Cucurbitacin-D (Cur-D), in HIV-infected macrophages using an in-vitro blood-brain barrier (BBB) model. Since tobacco smoking is prevalent in the HIV population, and it exacerbates HIV replication, we also tested the effect of Cur-D against cigarette smoke condensate (CSC)-induced HIV replication. Our results showed that Cur-D treatment reduces the viral load in a dose-dependent (0-1 µM) manner without causing significant toxicity at <1 µM concentration. Further, a daily dose of Cur-D (0.1 µM) not only reduced p24 in control conditions, but also reduced CSC (10 µg/mL)-induced p24 in U1 cells. Similarly, Cur-D (single dose of 0.4 µM) significantly reduced the CSC (single dose of 40 µg/mL)-induced HIV replication across the BBB model. In addition, treatment with Cur-D reduced the level of pro-inflammatory cytokine IL-1ß. Therefore, Cur-D, as an adjuvant therapy, may be used not only to suppress HIV in the brain, but also to reduce the CNS toxicity of currently existing ARVs.

Telemedicine as a tool for dietary intervention in NAFLD-HIV patients during the COVID-19 lockdown: A randomized controlled trial.

BACKGROUND & AIMS: Given reports of changes in dietary habits during covid-19 lockdown, our aim was to assess weight changes, over a 3-month Covid-19 national lockdown in a cohort of NAFLD-HIV patients on a dietary intervention trial. METHODS: After NAFLD screening in an outpatient Infectious Diseases Clinic, NAFLD patients were randomly allocated to general dietary recommendations (SC group) or to a structured dietary intervention based on the Mediterranean diet (intervention group). During lockdown, follow-up consultations in the intervention group were done by video and/or phone. After 3 months of lockdown, all patients (intervention and SC group) consented to a telephone interview which aimed to characterize eating habits and lifestyle changes and evaluate stress and depression. Biochemical data when available, was compared between the peri-period of confinement. RESULTS: One hundred and twelve patients were screened. From the 55 NAFDL identified, 27 were allocated to dietary intervention and 28 to SC and were followed before lockdown for a mean period of 5.0 ± 1.5 months in which SC group gained a median of 0.65 kg vs. a median loss of 1.5 kg in the intervention group (p < 0.001). During lockdown, 93.3% of patients in the SC group referred that "diet got worse" vs. 6.7% in the intervention group p < 0.01), and 35.3% vs. 15.7% (p = 0.014) reported increase in appetite, respectively. Both groups gained weight, SC group vs. 0.7 ± 1.7 kg in the intervention group, p < 0.001). Higher weight gain was associated with changes in the dietary pattern (3.8 ± 2.1 kg vs. 2.0 ± 1.3 kg in "no change in dietary pattern"; p = 0.002). Glucose blood levels increased after lockdown in the SC group, with a mean increase of 15 mg/dl (p = 0.023). The remaining metabolic parameters remained unchanged. CONCLUSION: The maintenance of dietary intervention, using telemedicine, can mitigate the adverse change in dietary habits and physical activity pattern, preventing a substantial increase in body weight.

Adherence to a Supplemented Mediterranean Diet Drives Changes in the Gut Microbiota of HIV-1-Infected Individuals.

OBJECTIVE: The health effects of a supplemented Mediterranean diet (SMD) with extra-virgin olive oil (EVOO) and nuts are well documented in non-HIV-infected individuals. We hypothesised that the benefits of an SMD could be mediated by changes in the gut microbiota, even in those with an altered intestinal microbiota such as people living with HIV. DESIGN: Individuals living with HIV (n = 102) were randomised to receive an SMD with 50 g/day of EVOO and 30 g/day of walnuts (SMD group) or continue with their regular diet (control group) for 12 weeks. METHODS: Adherence to the Mediterranean diet was assessed using the validated 14-item MD-Adherence-Screener (MEDAS) from the PREDIMED study. A sub-study classifying the participants according to their MEDAS scores was performed. RESULTS: The lipid profile was improved in the SMD group vs. that in the control group (delta-total cholesterol and delta-B-lipoprotein). The immune activation (CD4+HLADR+CD38+ and CD8+HLADR+CD38+ cells) and IFN-γ-producing T-cells significantly decreased at week 12 compared to the baseline in the SMD group but not in the control group. The gut microbiota in those from the high-adherence group presented significantly high diversity and richness at the end of the intervention. Succinivibrio and Bifidobacterium abundances were influenced by the adherence to the MD and significantly correlated with Treg cells. CONCLUSION: The Mediterranean diet improved metabolic parameters, immune activation, Treg function, and the gut microbiota composition in HIV-1-infected individuals. Further, Mediterranean diet increased the Bifidobacterium abundances after the intervention, and it was associated to a beneficial profile.

Long-acting injectable HIV therapies: the next frontier.

PURPOSE OF REVIEW: There has been significant development of long-acting injectable therapy for the management of HIV in recent years that has the potential to revolutionise HIV care as we know it. This review summarises the data and outlines the potential challenges in the field of long-acting antiretroviral therapy (ART). RECENT FINDINGS: In recent years, monthly and two monthly long-acting injectable ART in the form of cabotegravir and rilpivirine has shown safety and efficacy in large-scale phase 3 randomised control trials. Also, agents with novel mechanisms of action, such as Lenacapavir, have been tested in early-phase studies and are currently being tested in phase 2-3 clinical trials; if successful, this may allow six-monthly dosing schedules. SUMMARY: However, despite evidence that suggests that these therapies are efficacious and acceptable to patients, the challenge of integrating these agents into our current healthcare infrastructure and making these novel agents cost-effective and available to the populations most likely to benefit remains. The next frontier for long-acting therapy will be to introduce these agents in a real-world setting ensuring that the groups most in need of long-acting therapy are not left behind.

Increased Frequencies of Myeloid-Derived Suppressor Cells Precede Immunodiscordance in HIV-Infected Subjects.

Background: We have previously observed increased levels of inflammatory biomarkers and Th17 as well as Treg cells, but not other T-cell specific alterations, preceding immunodiscordance of successfully-treated HIV-infected subjects. Our hypothesis is that this could be related with potential alterations in myeloid-derived suppressor cells (MDSCs) and/or monocyte subsets. Methods: We determined the frequencies of MDSCs and monocyte subsets and the expression of several functional markers (CCR2, ß7-integrin, IDO, PDL1, CD11b) in HIV-infected subjects before treatment. We additionally analyzed follow-up samples after 24 months of suppressive cART in a subgroup of subjects. Bivariate regressions were performed, and correlations with soluble proinflammatory and bacterial translocation biomarkers, as well as with Th17/Treg ratio and anti-CMV titers were explored. Results: Increased frequencies of MDSCs, but normal distribution of monocyte subsets, preceded immunodiscordance. The expression of several functional markers, such as CCR2, CD16, CD11b and PDL1, on MDSCs and monocyte subsets was altered in this scenario. MDSC and monocyte-related functional markers were associated with soluble biomarkers and T-cell parameters. Several of these cellular alterations were not restored after 24 months of suppressive cART. Conclusion: An early immunosuppressive environment, characterized by the expansion of MDSCs and Tregs, precedes immunodiscordance and is related with a highly inflammatory status.

The effects of omega-3 fatty acid supplementation on inflammatory factors in HIV-infected patients: A systematic review and meta-analysis of randomized clinical trials.

High concentrations of C-reactive protein (CRP) and inflammatory markers are common in human immunodeficiency virus (HIV)-infected patients and are associated with non-HIV related comorbidity and mortality. Data on the benefits of omega-3 fatty acid (omega-3 FA) supplementation for improving inflammation status in HIV-infected patients are controversial. Thus, we conducted a systematic review and meta-analysis on the beneficial effects of omega-3 FAs on controlling inflammation in HIV-infected patients. We conducted a comprehensive search of the major biomedical databases, including PubMed, EMBASE, Scopus, Web of Science and Cochrane library, for all potentially relevant studies published without restriction from the beginning of time to June 2020. Overall, nine RCTs were included comprising a total of 427 participants. A random-effects model was used to calculate 95% confidence intervals (CI) and the effect was measured as standardized mean difference (SMD). Supplementation of omega-3 FAs showed a significant reduction of CRP (SMD: -0.27, 95% CI: -0.48 to -0.07, P = 0.007). There was no significant difference in levels of TNF-α (SMD: 0.03, 95% CI: -0.79 to 0.85, P = 0.94, I2 = 87%) and IL-6 (SMD: -0.13, 95% CI: -0.59 to 0.32, P = 0.57, I2 = 73%, Fig. 3). The results indicate that the supplementation of omega-3 FAs in HIV-infected patients significantly decreases serum CRP levels when compared to the control group, however has no significant effect on IL-6 and TNF-α levels.

Marginal structural models for repeated measures where intercept and slope are correlated: An application exploring the benefit of nutritional supplements on weight gain in HIV-infected children initiating antiretroviral therapy.

BACKGROUND: The impact of nutritional supplements on weight gain in HIV-infected children on antiretroviral treatment (ART) remains uncertain. Starting supplements depends upon current weight-for-age or other acute malnutrition indicators, producing time-dependent confounding. However, weight-for-age at ART initiation may affect subsequent weight gain, independent of supplement use. Implications for marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) are unclear. METHODS: In the ARROW trial, non-randomised supplement use and weight-for-age were recorded monthly from ART initiation. The effect of supplements on weight-for-age over the first year was estimated using generalised estimating equation MSMs with IPTW, both with and without interaction terms between baseline weight-for-age and time. Separately, data were simulated assuming no supplement effect, with use depending on current weight-for-age, and weight-for-age trajectory depending on baseline weight-for-age to investigate potential bias associated with different MSM specifications. RESULTS: In simulations, despite correctly specifying IPTW, omitting an interaction in the MSM between baseline weight-for-age and time produced increasingly biased estimates as associations between baseline weight-for-age and subsequent weight trajectory increased. Estimates were unbiased when the interaction between baseline weight-for-age and time was included, even if the data were simulated with no such interaction. In ARROW, without an interaction the estimated effect was +0.09 (95%CI +0.02,+0.16) greater weight-for-age gain per month's supplement use; this reduced to +0.03 (-0.04,+0.10) including the interaction. DISCUSSION: This study highlights a specific situation in which MSM model misspecification can occur and impact the resulting estimate. Since an interaction in the MSM (outcome) model does not bias the estimate of effect if the interaction does not exist, it may be advisable to include such a term when fitting MSMs for repeated measures.

Stigma and discrimination: barriers to the utilisation of a nutritional program in HIV care services in the Tigray region, Ethiopia.

BACKGROUND: In Ethiopia, stigmatising attitudes towards people living with HIV have reduced over time. This is mainly due to improved HIV knowledge and the expansion of access to HIV care and support services. However, HIV stigma and discrimination remain a key challenge and have negative impacts on access to and utilisation of HIV services including nutritional programs in the HIV care setting. A small number of studies have examined the experience of stigma related to nutritional programs, but this is limited. This study explored HIV status disclosure and experience of stigma related to a nutritional program in HIV care settings in Ethiopia and impacts on nutritional program utilisation. METHODS: As part of a larger study, qualitative in-depth interviews were conducted with 20 adults living with HIV, 15 caregivers of children living with HIV and 13 program staff working in the nutritional program in three hospitals in the Tigray region of Northern Ethiopia. Framework thematic analysis was employed to analyse the data and NVivo 11 was used to analyse the qualitative interview data. This study is presented based on the consolidated criteria for reporting of qualitative research (COREQ). RESULTS: The study found varying levels of positive HIV status disclosure, depending on who the target of disclosure was. Disclosing to family members was reported to be less problematic by most participants. Despite reported benefits of the nutritional program in terms of improving weight and overall health status, adults and caregivers of children living with HIV revealed experiences of stigma and discrimination that were amplified by enrolment to the nutritional program and concerns about unwanted disclosure of positive HIV status. This was due to: a) transporting, consuming and disposing of the nutritional support (Plumpynut/sup) itself, which is associated with HIV in the broader community; b) required increased frequency of visits to HIV services for those enrolled in the nutritional program and associated greater likelihood of being seen there. CONCLUSION: There was evidence of concerns about HIV-related stigma and discrimination among individuals enrolled in this program and their family members, which in turn negatively affected the utilisation of the nutritional program and the HIV service more broadly. Stigma and discrimination are a source of health inequity and undermine access to the nutritional program and other HIV services. Nutritional programs in HIV care should include strategies to take these concerns into account by mainstreaming stigma prevention and mitigation activities. Further research should be done to identify innovative ways of facilitating social inclusion to mitigate stigma and improve utilisation.

Serum Trimethylamine-N-oxide Concentrations in People Living with HIV and the Effect of Probiotic Supplementation.

BACKGROUND: The incidence of cardiovascular disorders in people living with HIV (PLWH) is higher than that in non-infected individuals. Traditional and specific risk factors have been described but the role of the gut microbiota-dependent choline metabolite, trimethylamine-N-oxide (TMAO) is still unclear. METHODS: A cross-sectional analysis and a longitudinal analysis (with high-dose probiotic supplementation) were performed to measure serum TMAO concentrations through UHPLC-MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non-parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used. RESULTS: A total of 175 participants were enrolled in the study. Median serum TMAO concentrations were 165 (103-273) ng/mL. An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed; at linear logistic regression analysis, multimorbidity was the only independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 (0.71-1.21) mm, with a trend towards higher TMAO concentrations observed in patients with IMT >0.9 mm (P=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significantly change after 24 weeks (Wilcoxon paired P=0.220). CONCLUSION: Serum TMAO levels in PLWH were associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis and were not affected by 6 months of high-dose probiotic supplementation.

Effect of vitamin D3 supplementation on HIV-infected adults: a systematic reviewVitamin D? Supplementation on HIV-Infected Adults: A Systematic Review / Efecto de la suplementación con vitamina D3 en adultos infectados por el VIH: una revisión sistemática

Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections

Introducción: muchas evidencias ratifican que la vitamina D puede estar asociada con la mejora de los niveles de células CD4 en individuos infectados por el VIH, tratados con terapia antirretroviral (ART) que se asocia a la disminución de los niveles de 25(OH)D. Objetivo: realizar una revisión sistemática sobre el efecto de la suplementación de vitamina D en pacientes adultos infectados con VIH. Métodos: la investigación fue realizada en las bases de datos Science Direct, PubMed, BVS, Scielo Cochrane y periódicos, de febrero a abril de 2018, con límite de publicación de 2000 a 2018, sin restricción de género, etnicidad y que involucra a individuos con edad mayores de 18 años. Para la evaluación de la calidad de los estudios, se utilizó el protocolo Preferred Reporting Items for Systematic Reviews y Meta-Analyzes (PRISMA) y la escala de Jadad. Resultados: la encuesta inicialmente resultó en 198 artículos. Después del proceso de selección, 5 artículos fueron identificados como elegibles, donde ponen de manifiesto que la suplementación con vitamina D puede ser una intervención asociada y eficaz para reducir la hipovitaminosis. La ART reduce niveles de la vitamina D3 y altera su metabolismo, estando asociada al riesgo de mortalidad. Sin embargo, los niveles adecuados de 25(OH)D están asociados positivamente al número de células CD4 + y la reducción de los niveles de infecciones. Conclusión: la suplementación de vitamina D promueve la recuperación inmunológica. Sin embargo, los casos analizados fueron pocos, insuficientes para confirmar totalmente los beneficios y recomendar la suplementación. Por lo tanto, estudios de intervención son necesarios para elucidar la actuación de la vitamina D en la protección humana contra las infecciones por el VIH

Use of Dolutegravir for Antiretroviral Therapy for Women of Childbearing Age.

The purpose of this article is to offer an update on the use of antiretroviral therapy (ART) for HIV among women of childbearing age. We focus specifically on the use of dolutegravir (DTG) because of a recently identified potential safety issue related to neural tube defects in the fetuses of women who used DTG at the time of conception. Nurses and advanced practice registered nurses should engage in shared decision-making processes for reproductive life planning with women of childbearing age who are living with or are at risk for HIV. During these processes, exploration of the full range of ART regimens is essential. Consistent and reliable contraception is necessary with the use of DTG because it is not recommended in the first trimester of pregnancy.

The effect of HIV infection, antiretroviral therapy on carotid intima-media thickness: A systematic review and meta-analysis.

AIMS: We performed a systematic review and meta-analysis on the effect of HIV infection and antiretroviral therapy (ART) on carotid intima-media thickness (cIMT) to elucidate the role of HIV infection and ART. Also, an analysis on the role of ethnicity and gender on cIMT in HIV-infected populations was performed. MAIN METHODS: We searched the PubMed, Web of Science, the WHO websites and International AIDS Society for published observational studies were conducted by two independent reviewers for studies comparing HIV-infected antiretroviral-experienced patients and/or inexperienced with healthy controls on cIMT. The primary outcome was the standardized mean difference (SMD) of cIMT. FINDINGS: Twenty studies (five cohort, 15 cross-sectional, and two both cohort and cross-sectional studies) were identified comprising 7948 subjects (4656 HIV-infected; 3292 controls). In cohort studies, the standardized mean 1-year change in cIMT between HIV-infected patients and uninfected controls was not significantly different (0.16 mm/yr; 95% CI, -0.16, 0.49; p = 0.326). In 17 cross-sectional studies, the SMD in cIMT was significantly higher in HIV-infected than uninfected persons (0.27 mm; 95% CI, 0.04, 0.49; p = 0.027). HIV-infected patients on ART exhibited significantly higher SMD in cIMT compared to those not on ART (0.75 mm; 95% CI, 0.30, 1.19; p = 0.001). No confounding effect of gender and ethnicity could be established using meta-regression p > 0.05. SIGNIFICANCE: HIV infection itself and ART appear to influence the progression of cIMT and hence may be risk factors for cardiovascular events. No firm conclusions could be drawn on the effect of ethnic/race and gender differences on cIMT in HIV-infected populations.

Nutrition support for HIV-TB co-infected adults in Senegal, West Africa: A randomized pilot implementation study.

BACKGROUND: Food insecurity can contribute to poor adherence to both tuberculosis treatment and HIV antiretroviral therapy (ART). Interventions that target food insecurity have the potential to increase treatment adherence, improve clinical outcomes, and decrease mortality. The goals of this study were to compare the feasibility, acceptability, and potential impact of implementing two different forms of nutrition support for HIV-TB co-infected adults in the Casamance region of Senegal. METHODS: We conducted a randomized pilot implementation study among HIV-TB co-infected adults initiating treatment for TB (ClinicalTrials.gov Identifier: NCT03711721). Subjects received nutrition support in the form of a local food basket or Ready-to-Use Therapeutic Food (RUTF), distributed on a monthly basis for six months. RESULTS: A total of 178 monthly study encounters were completed by 26 HIV-TB co-infected adults; 14 received food baskets and 12 received RUTF. For both the food basket and RUTF, 100% of subjects obtained the supplement at every study encounter, transferred the supplement from the clinic to their household, and consumed the supplement. The food basket had greater acceptability and was more likely to be shared with members of the household. Adherence to TB treatment and ART exceeded 95%, and all outcomes, including CD4 cell count, hemoglobin, nutritional status, and food security, improved over the study period. All subjects completed TB treatment and were smear negative at treatment completion. The total cost of the local food basket was approximately $0.68 per day versus $0.99 for the RUTF. CONCLUSION: The implementation of nutrition support for HIV-TB co-infected adults in Senegal is feasible and may provide an effective strategy to improve adherence, treatment completion, and clinical outcomes for less than 1 USD per day. Further studies to determine the impact of nutrition support among a larger population of HIV-TB co-infected individuals are indicated.

Modulation of Saliva Microbiota through Prebiotic Intervention in HIV-Infected Individuals.

Human immunodeficiency virus (HIV) infection is characterized by an early depletion of the mucosal associated T helper (CD4+) cells that impair the host immunity and impact the oral and gut microbiomes. Although, the HIV-associated gut microbiota was studied in depth, few works addressed the dysbiosis of oral microbiota in HIV infection and, to our knowledge, no studies on intervention with prebiotics were performed. We studied the effect of a six-week-long prebiotic administration on the salivary microbiota in HIV patients and healthy subjects. Also, the co-occurrence of saliva microorganisms in the fecal bacteria community was explored. We assessed salivary and feces microbiota composition using deep 16S ribosomal RNA (rRNA) gene sequencing with Illumina methodology. At baseline, the different groups shared the same most abundant genera, but the HIV status had an impact on the saliva microbiota composition and diversity parameters. After the intervention with prebiotics, we found a drastic decrease in alpha diversity parameters, as well as a change of beta diversity, without a clear directionality toward a healthy microbiota. Interestingly, we found a differential response to the prebiotics, depending on the initial microbiota. On the basis of 100% identity clustering, we detected saliva sequences in the feces datasets, suggesting a drag of microorganisms from the upper to the lower gastrointestinal tract.

Sustained Effect of a Community-based Behavioral and Nutrition Intervention on HIV-related Outcomes Among Women Living With HIV in Rural India: A Quasi-experimental Trial.

BACKGROUND: Women living with HIV (WLH) in rural communities face challenges to obtaining treatment and accurate disease-related information. Nutritional deficits exacerbate disease progression. SETTING: WLH were recruited from primary health centers in rural India. METHOD: A quasi-experimental trial of a comprehensive Accredited Social Health Activist (Asha)-supported intervention compared 4 distinct Asha-based programs [(1) standard education (SE) alone; (2) nutrition education (+NE); (3) nutrition supplements (+NS); or (4) nutrition education and nutrition supplements (+NENS)] on key disease and nutrition-related outcomes [CD4 count, body mass index (BMI), serum albumin, and hemoglobin]. Assessments occurred at baseline, and months 6 (immediately after intervention), 12, and 18. Multilevel modeling examined effects of program (group) over time. FINDINGS: Among 600 WLH enrolled (n = 150 per arm), mean age, CD4 count, and BMI (kg/m) were 34.31, 447.42, and 20.09, respectively, at baseline. At 18-month follow-up, program 4 (+NENS) experienced greatest improvements in CD4 counts compared with program 1 (+SE) [adjusted difference = 223.81, 95% confidence interval (CI): 170.29 to 277.32]. For BMI, programs 3 (+NS; adjusted difference = 2.33, 95% CI: 1.39 to 3.26) and 4 (+NENS; adjusted difference = 2.14, 95% CI: 1.17 to 3.12) exhibited greater gains compared with program 1 (+SE). Programs 3 and 4 were not significantly different from each other (adjusted difference = -0.18, 95% CI: -1.12 to 0.76). Hemoglobin and serum albumin also improved over time; program 4 (+NENS) exhibited the greatest gains. CONCLUSIONS: A low-cost Asha-supported behavioral and nutritional intervention improved outcomes for WLH. Gains were sustained at 18-month follow-up. Similar approaches may help improve HIV and other infectious disease-related outcomes in vulnerable populations.

"I do my best to eat while I'm using": Mapping the foodscapes of people living with HIV/AIDS who use drugs.

Food insecurity can have negative health impacts on people who use drugs and are living with HIV/AIDS (PLHIV). These include both physical effects, including poorer health outcomes and morbidity, and also behaviors that can increase the risk of physical or psychological harm. This study used a semi-structured survey of 60 PLHIV who use drugs and service access mapping (SAM) interviews of a 20-person subset. The mapping helped to illustrate the daily routines used to access food and how food provision may contribute to both spaces of risk and care for a cohort of PLHIV who use drugs in Vancouver, BC. Study participants mapped the daily routes used to access food and discussed whether they felt that these routines increased their risk of physical harm. Additionally, study participants noted which food provision spaces provide social and health supports, which may protect against the nutritional and other harms of drug use. This study revealed that having access to space providing stable and reliable sources of food may protect individuals from experiencing certain risks associated with accessing food, including violence in food line-ups, having to enter areas of the city they considered unsafe or 'triggering' and engaging in risky behaviors in order to access food. These "spaces of care" not only provide nutrition but also social support and connections.

The Use of the Restricted Mean Survival Time as a Treatment Measure in HIV/AIDS Clinical Trial: Reanalysis of the ACTG A5257 Trial.

BACKGROUND: The restricted mean survival time (RMST) measures have not been used as primary measure of efficacy in HIV/AIDS clinical trials. In this work, we aim to compare analysis based on the difference in RMST (Δ-RMST) measure and 2 other treatment-effect measures in a recent HIV equivalence trial, and to investigate the performance and characteristics of Δ-RMST-based analysis in a simulation study. SETTING AND METHODS: We reanalyzed a recent HIV equivalence trial (ACTG A5257 trial) with hazard ratio and Δ-RMST, and then compared the results with the original analysis based on risk difference estimated by Kaplan-Meier curves (RDKM). In a simulation study, we investigated the performance and operating characteristics of Δ-RMST-based analysis in the setting of non-proportional hazards (PH) ratio. RESULTS: In the ACTG A5257 trial, analyses based on Δ-RMST globally led to similar conclusions as the published finding based on RDKM. By contrast, analyses based on hazard ratio provided some discordant equivalence conclusions compared both with the initial analyses based on RDKM and the Δ-RMST. Results of simulation study indicate that the violation of the PH assumption has an impact on Δ-RMST-based analysis regarding the probability of declaring equivalence. CONCLUSIONS: Although the RMST-based analysis is an alternative measure of efficacy in HIV/AIDS, clinical trials such an analysis can be strongly impacted by departures from the PH assumption.