-
1.
Adherence to a Supplemented Mediterranean Diet Drives Changes in the Gut Microbiota of HIV-1-Infected Individuals.
Pastor-Ibáñez, R, Blanco-Heredia, J, Etcheverry, F, Sánchez-Palomino, S, Díez-Fuertes, F, Casas, R, Navarrete-Muñoz, MÁ, Castro-Barquero, S, Lucero, C, Fernández, I, et al
Nutrients. 2021;(4)
Abstract
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.
-
2.
Brief Report: Improvement in Metabolic Health Parameters at Week 48 After Switching From a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen to the 2-Drug Regimen of Dolutegravir/Lamivudine: The TANGO Study.
van Wyk, J, Ait-Khaled, M, Santos, J, Scholten, S, Wohlfeiler, M, Ajana, F, Jones, B, Nascimento, MC, Tenorio, AR, Smith, DE, et al
Journal of acquired immune deficiency syndromes (1999). 2021;(2):794-800
-
-
Free full text
-
Abstract
BACKGROUND In TANGO, switching to dolutegravir/lamivudine was noninferior at 48 weeks to continuing 3-/4-drug tenofovir alafenamide-based regimens in virologically suppressed individuals with HIV-1. Antiretroviral agents have been associated with weight gain and metabolic complications. SETTING One hundred thirty-four centers; 10 countries. METHODS We assessed weight; fasting lipids, glucose, and insulin; and prevalence of insulin resistance and metabolic syndrome at baseline and week 48 in TANGO participant subgroups by boosting agent use in baseline regimens (boosted and unboosted). RESULTS In each treatment group, 74% of participants used boosted regimens at baseline. In boosted and unboosted subgroups, weight and fasting glucose changes at week 48 were small and similar between treatment groups. Overall and in the boosted subgroup, greater decreases from baseline were observed with dolutegravir/lamivudine in fasting total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), total cholesterol/high-density lipoprotein cholesterol ratio (overall, P = 0.017; boosted, P = 0.007), and insulin (boosted, P = 0.005). Prevalence of HOMA-IR ≥2 was significantly lower at week 48 with dolutegravir/lamivudine overall [adjusted odds ratio (aOR), 0.59; 95% confidence interval (CI), 0.40 to 0.87; P = 0.008] and in the boosted subgroup [aOR, 0.56; 95% CI, 0.36 to 0.88; P = 0.012] but not in the unboosted subgroup [aOR, 0.70; 95% CI, 0.31 to 1.58; P = 0.396]. Prevalence of metabolic syndrome at week 48 was low and consistent between treatment groups overall, with differences trending to favor dolutegravir/lamivudine in the unboosted subgroup [aOR, 0.41; 95% CI, 0.15 to 1.09; P = 0.075]. CONCLUSION Generally, switching from 3-/4-drug tenofovir alafenamide-based regimens to dolutegravir/lamivudine improved metabolic parameters, particularly when switching from boosted regimens. Because of smaller sample size in the unboosted subgroup, results warrant further investigation.
-
3.
Impact of postpartum tenofovir-based antiretroviral therapy on bone mineral density in breastfeeding women with HIV enrolled in a randomized clinical trial.
Stranix-Chibanda, L, Tierney, C, Sebikari, D, Aizire, J, Dadabhai, S, Zanga, A, Mukwasi-Kahari, C, Vhembo, T, Violari, A, Theron, G, et al
PloS one. 2021;(2):e0246272
Abstract
OBJECTIVES We set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV. DESIGN IMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858). METHODS IMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented. RESULTS Among 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value <0.001). Similarly, maternal hip bone mineral density declined significantly more through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference -2.29% (-3.20, -1.39) (p-value <0.001). Adjusting for covariates did not change the treatment effect. CONCLUSIONS Bone mineral density decline through week 74 postpartum was greater among breastfeeding HIV-infected women randomized to receive maternal TDF-ART during breastfeeding compared to those mothers whose infants received nevirapine prophylaxis.
-
4.
Combination of resistance and aerobic exercise for six months improves bone mass and physical function in HIV infected individuals: A randomized controlled trial.
Ghayomzadeh, M, Earnest, CP, Hackett, D, SeyedAlinaghi, S, Navalta, JW, Gholami, M, Hosseini Rouzbahani, N, Mohraz, M, Voltarelli, FA
Scandinavian journal of medicine & science in sports. 2021;(3):720-732
Abstract
To evaluate the effect of combined resistance and aerobic training (RT+AT) on regional bone mineral density (BMD) and physical performance in people living with HIV (PLWH). Forty PLWH (20 men and 20 women) were randomized into RT+AT group (n = 20; age = 38.3 ± 4.9) or non-exercise control group (n = 20; age = 37.9 ± 5.1). The RT+AT group was required to perform a nonlinear periodized resistance training program targeting large muscle groups followed by 20 min aerobic exercise at 65-80% of maximal heart rate. Participants in RT+AT performed three supervised sessions per week for 6-months, whereas participants in the control group were instructed to continue with their current lifestyle habits. The primary outcome was bone mineral density (lumbar spine (L2-L4), femoral neck, and distal 1/3 radius). Secondary outcomes included physical function, anthropometry, inflammatory markers, and growth factors. The RT+AT group demonstrated a significant increase in BMD at follow-up for the Lumbar spine (L2-L4), femoral neck, and 1/3 radius (all, P < .05), and There were no gender differences in the training response between men and women for any of the BMD regions. Similar findings were also observed for lean body mass, IGF1and Adiponectin (P < .001). We observed a decrease in percent body fat, fat mass, IL-6, TNF-α, and myostatin in the RT+AT group (P < .001). Finally, there was a significant increase in handgrip strength and gait speed for both women and men in the RT+AT group (P < .001). A combination of resistance and aerobic training appears to be a feasible and effective means for counteracting bone loss and improving various inflammatory markers, physical function, and growth hormones in PLWH.
-
5.
Brief Report: Impact of ART on Maternal Health After Cessation of Breastfeeding.
Brummel, SS, Taha, TE, Angelidou, KN, Saidi, F, Atuhaire, P, Dula, D, Moodley, D, Matubu, A, Chareka, G, Nevrekar, N, et al
Journal of acquired immune deficiency syndromes (1999). 2021;(4):450-454
-
-
Free full text
-
Abstract
IMPAACT PROMISE 1077BF/FF was a sequentially randomized study of pregnant and postpartum women living with HIV to investigate the efficacy and safety of antiretroviral therapy (ART). This Maternal Health Component investigated efficacy for the risk of developing AIDS or death; and safety among women randomized to continue ART (CTART N = 289) or discontinue ART (N = 268) after cessation of breastfeeding or after confirmation of infant infection. No AIDS-defining illnesses were reported during follow-up in either arm. Adverse events of grade 3 or higher were more frequent in the CTART arm [hazard ratio = 1.78, 95% confidence interval: (1.05 to 3.02), P-value = 0.03]. The difference in adverse events in the 2 groups was mostly driven by moderate weight loss for women on the CTART arm.
-
6.
Effects of selenium supplementation on pregnancy outcomes and disease progression in HIV-infected pregnant women in Lagos: A randomized controlled trial.
Okunade, KS, Olowoselu, OF, John-Olabode, S, Hassan, BO, Akinsola, OJ, Nwogu, CM, Ugwu, AO, Moses, OE, Rabiu, KA, Ajepe, A, et al
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021;(3):533-541
-
-
Free full text
-
Abstract
OBJECTIVE To examine the effects of selenium supplementation on pregnancy outcomes and disease progression among HIV-infected pregnant women in Lagos. METHODS A randomized, placebo-controlled trial conducted among HIV-positive pregnant women between September 2018 and August 2019. At enrollment, 90 women were randomly assigned into each treatment arm to receive either a daily tablet of 200 μg elemental selenium or a placebo. Relevant participants' sociodemographic and clinical data were collected at enrollment and delivery. RESULTS Women in the selenium arm had a significantly lower risk of preterm delivery (relative risk [RR] 0.32, 95% confidence interval [CI] 0.11-0.96) and a non-significant reduction in the risk of delivering term neonates with a low delivery weight (RR 0.24, 95% CI 0.05-1.19). Supplemental selenium does not increase the risk of perinatal death and adverse drug events. CONCLUSION The study reported a beneficial effect of prenatal selenium supplements on the risk of preterm delivery with no further reduction in risk among HIV-infected women who used the supplements for more than 14 weeks. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201809756724274).
-
7.
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial.
Madhi, SA, Koen, AL, Izu, A, Fairlie, L, Cutland, CL, Baillie, V, Padayachee, SD, Dheda, K, Barnabas, SL, Bhorat, QE, et al
The lancet. HIV. 2021;(9):e568-e580
Abstract
BACKGROUND People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. METHODS In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. INTERPRETATION ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. FUNDING The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.
-
8.
Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals.
Nogueira Soares, R, Machado-Santos, AP, Barros-Santos, E, Vieira De Oliveira, G, Murias, JM, Alvares, TS
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(3):213-220
Abstract
Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for cardiovascular disease. Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. Thirteen HIV-infected individuals (age, 36 ± 10 years) and 18 healthy (age, 27 ± 8 years) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after BJ and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared with T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120), and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich BJ ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry no. NCT03485248. Novelty: HIV is associated with lower NO bioavailability and vascular dysfunction. Acute supplementation with nitrate-rich BJ has been shown to acutely increases NO bioavailability. We showed for the first time that BJ acutely improves endothelial function in HIV-infected patients.
-
9.
Randomized parallel-group pilot trial (Best foods for your heart) comparing the effects of a Mediterranean Portfolio diet with a low saturated fat diet on HIV dyslipidemia.
Stradling, C, Thomas, GN, Hemming, K, Taylor, S, Taheri, S
Clinical nutrition (Edinburgh, Scotland). 2021;(3):860-869
Abstract
BACKGROUND & AIMS Mediterranean diets reduce the risk of cardiovascular disease (CVD). However, the effect is unknown in people living with HIV, who have an increased risk potentially due to the additional burdens of infection, inflammation and antiretroviral treatment (ART). We examined the feasibility of a 6-month dietary intervention in adults with HIV dyslipidemia using a sample size adequate to detect differences in LDL-cholesterol. METHODS Sixty adults with stable HIV infection on ART and LDL-cholesterol >3 mmol/l were recruited. Participants were randomized (1:1) to receive dietary advice to reduce saturated fat intake to <10% of energy intake (Diet1), or supported to adopt the Mediterranean Portfolio Diet (Diet2) with additional cholesterol-lowering foods (nuts, stanols, soya, oats, beans) for 6 months. Recruitment, retention and intervention fidelity were monitored. Measurements were conducted at baseline, 6 and 12 months. A secondary analysis examined between group differences in CVD risk factors at month 6 adjusted for baseline values and potential confounders. RESULTS Rates of recruitment, participation and attrition were 35%, 91%, and 12% respectively. Reported dietary adherence was 68% to Mediterranean foods and 59% to Portfolio components. At 6 months Diet2 participants (n = 29) had a significantly lower LDL-cholesterol (mean difference adjusted for baseline -0.4 mmol/l, 95%CI -0.7 to -0.1, P = 0.01), and systolic blood pressure (-7 mmHg, 95%CI -2 to -12, P = 0.008) compared to those in Diet1 (n = 31). These effects were not sustained at 1 year (LDL-cholesterol -0.05 mmol/l, 95%CI -0.33 to 0.23, P = 0.7; systolic blood pressure -3.5 mmHg, 95%CI -9.4 to 2.5, P = 0.2). CONCLUSION We showed the feasibility of adopting a Mediterranean Portfolio diet in people living with HIV. Our findings suggest this intervention might equate to short term improvements in diet quality, blood pressure, and LDL-cholesterol. Further definitive evaluations are required to determine if this is a viable strategy to facilitate cardiovascular risk reduction. CLINICAL TRIAL REGISTRY ISRCTN32090191 Best Foods For your heart trial.
-
10.
Standard dose raltegravir or efavirenz-based antiretroviral treatment for patients co-infected with HIV and tuberculosis (ANRS 12 300 Reflate TB 2): an open-label, non-inferiority, randomised, phase 3 trial.
De Castro, N, Marcy, O, Chazallon, C, Messou, E, Eholié, S, N'takpe, JB, Bhatt, N, Khosa, C, Timana Massango, I, Laureillard, D, et al
The Lancet. Infectious diseases. 2021;(6):813-822
Abstract
BACKGROUND In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug-drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. METHODS We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration <50 copies per mL). The prespecified non-inferiority margin was 12%. The primary outcome was assessed in the intention-to-treat population, which included all randomly assigned patients (excluding two patients with HIV-2 infection and one patient with HIV-1 RNA concentration of <50 copies per mL at inclusion), and the on-treatment population, which included all patients in the intention-to-treat population who initiated treatment and were continuing allocated treatment at week 48, and patients who had discontinued allocated treatment due to death or virological failure. Safety was assessed in all patients who received at least one dose of the assigned treatment regimen. This study is registered with ClinicalTrials.gov, NCT02273765. FINDINGS Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per μL and median plasma HIV RNA concentration was 5·5 log10 copies per mL (IQR 5·0-5·8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5·2% [95% CI -14·0 to 3·6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group. INTERPRETATION In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients. FUNDING National French Agency for AIDS Research, Ministry of Health in Brazil, Merck. TRANSLATIONS For the Portuguese and French translations of the abstract see Supplementary Materials section.