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HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis. ClinicalTrials.gov NCT02164344.

HIV/AIDS may cause malnutrition, both directly and indirectly, through common infections. This systematic review and meta-analysis aim to evaluate the effects of nutritional interventions on nutritional status, immunological status, adherence to antiretroviral treatment (ART), and food security among people living with HIV/AIDS (PLWHA) in low- and middle-income countries (LMICs). Five databases-MEDLINE, Embase, Scopus, Web of Science, and CENTRAL-were searched for articles on August 17, 2021, with an updated search conducted on September 30, 2023 to identify new records. Studies were considered eligible if they included adults living with HIV/AIDS who recently initiated ART, if they were controlled trials that provided nutritional interventions, and if they assessed the relevant nutritional, immunological and adherence outcomes. The effects of nutritional interventions were analyzed using a random-effects model. The systematic review comprised 22 articles from 12 LMICs, while the meta-analysis included 19 articles. The interventions provided lipid-based nutrient supplements, corn-soy blends, food baskets, conditional cash, prepared meals, micronutrient supplementation, and functional foods to PLWHA. Compared to controls, nutritional interventions for PLWHA significantly improved their body mass index (standardized mean difference, 95% confidence interval) (SMD 0.42; 95% CI: 0.03, 0.81; p =  0.03), fat mass (SMD 0.21; 95% CI: 0.07, 0.34; p =  0.002), fat-free mass (SMD 0.33; 95% CI: 0.19, 0.46; p <  0.0001), and CD4 (SMD 0.54; 95% CI: 0.01, 1.07; p =  0.05), but had no effect on their weight, viral load, or adherence to ART. The baseline nutritional and immunological characteristics of PLWHA, as well as the intervention characteristics, further modified these effects. Nutritional interventions improved some nutritional and immunological indicators but not ART adherence among PLWHA. Additionally, their effects were modified by some baseline characteristics and the type and duration of interventions which require consideration before its scaling up.

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. 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. 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. 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.

Introduction: The present study aimed to assess the nutritional status, the dietary patterns and its associated factors in the HIV-infected population of children and adolescents on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Methods: A cross-sectional survey was carried out between December 2010 and December 2011. Socio-demographic and clinical characteristics were collected from 307 children and adolescents aged 2-18 years and receiving antiretroviral therapy. Nutritional status was assessed by height-for-age, weight-for-height and body mass index-for-age. Dietary data was collected through a 24 hour recall, and through a weekly food frequency questionnaire. Dietary patterns were identified by principal component analysis. Bivariate and multivariable statistical methods were used to assess the factors associated with “high adherence” to the “healthy diet” pattern. Results: More than a third of the study group (33.2%) were stunted, 3.3% were identified as being wasted, and 10% were overweight or obese. Their diets were predominantly based on a high consumption of cereals, beans, eggs and processed foods and a low consumption of fruits, vegetables and dairy products. Three dietary patterns were identified: “healthy diet”, “high fat/sugar diet” and “low diversity diet”. Being female (OR: 1.63; 95%CI: 0.97-2.75), younger (OR: 2.37; 95%CI: 1.28-4.36) and institutionalized (OR: 14.5; 95%CI: 5.35-39.50) increased the odds to adhere to the “healthy diet” pattern. Conclusion: Our findings reveal a high prevalence of stunting and overweight in HIV-infected children in El Salvador. Institutionalized children were more likely to adhere to a healthy dietary pattern whereas children in poverty were more likely to have less varied and healthy diets. These results highlight the need to assess the dietary patterns of HIV-infected children and adolescents in order to guide public policies to design healthy life style interventions for this population at risk.

Food insecurity is associated with negative chronic health outcomes, yet few studies have examined how providing medically appropriate food assistance to food-insecure individuals may improve health outcomes in resource-rich settings. We evaluated a community-based food support intervention in the San Francisco Bay Area for people living with HIV and/or type 2 diabetes mellitus (T2DM) to determine the feasibility, acceptability, and potential impact of the intervention on nutritional, mental health, disease management, healthcare utilization, and physical health outcomes. The 6-month intervention provided meals and snacks designed to comprise 100% of daily energy requirements and meet nutritional guidelines for a healthy diet. We assessed paired outcomes at baseline and 6 months using validated measures. Paired t tests and McNemar exact tests were used with continuous and dichotomous outcomes, respectively, to compare pre-post changes. Fifty-two participants (out of 72 initiators) had both baseline and follow-up assessments, including 23 with HIV, 24 with T2DM, and 7 with both HIV and T2DM. Median food pick-up adherence was 93%. Comparing baseline to follow-up, very low food security decreased from 59.6% to 11.5% ( p  < 0.0001). Frequency of consumption of fats ( p  = 0.003) decreased, while frequency increased for fruits and vegetables ( p  = 0.011). Among people with diabetes, frequency of sugar consumption decreased ( p  = 0.006). We also observed decreased depressive symptoms ( p  = 0.028) and binge drinking ( p  = 0.008). At follow-up, fewer participants sacrificed food for healthcare ( p  = 0.007) or prescriptions ( p  = 0.046), or sacrificed healthcare for food ( p  = 0.029). Among people with HIV, 95% adherence to antiretroviral therapy increased from 47 to 70% ( p  = 0.046). Among people with T2DM, diabetes distress ( p  < 0.001), and perceived diabetes self-management ( p  = 0.007) improved. Comprehensive, medically appropriate food support is feasible and may improve multiple health outcomes for food-insecure individuals living with chronic health conditions. Future studies should formally test the impact of medically appropriate food support interventions for food-insecure populations through rigorous, randomized controlled designs.

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.

HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.

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. 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. 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. 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.

HLA-B*52:01-C*12:02, which is found in approximately 20% of all Japanese persons, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be protective in individuals infected with human immunodeficiency virus (HIV) type 1. Recent studies showed that HLA-B*52:01–restricted HIV-1–specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in natural killer cell–mediated control of HIV-1. However, the role of HLA-C*12:02–restricted cytotoxic T lymphocytes (CTLs) in suppressing HIV-1 replication remains unknown. In the present study, we demonstrated that HLA-C*12:02–restricted CTLs specific for 2 immunodominant epitopes, Pol IY11 and Nef MY9, contributed to the suppression of HIV-1 replication in HIV-1–infected individuals. Further analysis demonstrated that these 2 HLA-C*12:02–restricted CTLs together with 4 HLA-B*52:01–restricted ones effectively suppressed HIV-1 in individuals with the HLA-B*52:01-C*12:02 haplotype. Thus, both HLA-C*12:02 and HLA-B*52:01 alleles contribute to HIV-1 suppression via both HIV-1–specific CTLs and natural killer cells in individuals with this haplotype.

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-1β. 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.