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Health status, food insecurity, and time allocation patterns of patients with AIDS receiving antiretroviral treatment in South Africa.
Bhargava, A, Booysen, FLR, Walsh, CM
AIDS care. 2018;(3):361-368
Abstract
For patients with AIDS receiving antiretroviral treatment (ART) in South Africa via public clinics, improvements in nutritional status and economic productivity are likely to depend on adherence to drug regimen and quality of diet reflected in protein and micronutrient intakes. This study randomized 643 patients receiving ART from public clinics in the Free State Province into a Control group, a treatment group receiving adherence support, and a treatment group receiving adherence support and a nutritious food supplement. The data on food insecurity levels and time spent on various activities were analyzed for assessing the impact of the intervention programs. The main results were, first, changes between survey rounds 1 and 3 were significant at the 5% level for outcomes such as food insecurity levels and CD4 cell counts. Moreover, there was a significant reduction in food insecurity levels of patients with BMI less than 25 who received the nutritious food supplement. Second, the estimated parameters from models for patients' food insecurity levels showed that household incomes were significantly associated with lower food insecurity levels. Third, patients' BMI was a significant predictor of time spent on sedentary, moderate and overall activity levels, and it was important to separately evaluate the effects of BMI for under-weight and over-weight patients. Overall, the results indicated the need for reducing food insecurity levels, and for designing different interventions for under-weight and over-weight patients with AIDS for enhancing their labor productivity.
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Non-Alcoholic Fatty Liver Disease in Patients with HIV Infection.
Papagianni, M, Tziomalos, K
AIDS reviews. 2018;(3):171-173
Abstract
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with HIV infection and appears to be more severe than in HIV-uninfected patients. Both metabolic (e.g., obesity and insulin resistance) and HIV-related factors (e.g., antiretroviral treatment and inflammation) play a role in the pathogenesis of NAFLD in this population. Accordingly, all patients with HIV infection should be evaluated for the presence of NAFLD. Ultrasound is the first-line diagnostic procedure, but non-alcoholic steatohepatitis has to be diagnosed with liver biopsy. However, non-invasive methods, including serological markers and transient elastography, might also be useful in this population. Lifestyle changes represent the cornerstone of treatment. Bariatric surgery, pioglitazone, and vitamin E can be considered in patients with significant fibrosis or at high risk for progression of NAFLD, including those with type 2 diabetes mellitus, metabolic syndrome, elevated transaminases, or pronounced necroinflammation. However, there are no studies that evaluated the safety of efficacy of diet, exercise, or pharmacotherapy in this population. Therefore, research is needed to identify safe and effective pharmacological treatments for NAFLD in patients with HIV infection.
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Gut microbiota and plasma metabolites associated with diabetes in women with, or at high risk for, HIV infection.
Moon, JY, Zolnik, CP, Wang, Z, Qiu, Y, Usyk, M, Wang, T, Kizer, JR, Landay, AL, Kurland, IJ, Anastos, K, et al
EBioMedicine. 2018;:392-400
Abstract
BACKGROUND Gut microbiota alteration has been implicated in HIV infection and metabolic disorders. The relationship between gut microbiota and diabetes has rarely been studied in HIV-infected individuals, who have excess risk of metabolic disorders. METHODS Our study during 2015-2016 enrolled predominantly African Americans and Hispanics in the Women's Interagency HIV Study. We studied 28 women with long-standing HIV infection under antiretroviral therapy and 20 HIV-uninfected, but at high risk of infection, women (16 HIV+ and 6 HIV- with diabetes). Fecal samples were analyzed by sequencing prokaryotic16S rRNA gene. Plasma metabolomics profiling was performed by liquid chromatography-tandem mass spectrometry. FINDINGS No significant differences in bacterial α- or β-diversity were observed by diabetes or HIV serostatus (all P > .1). Relative abundances of four genera (Finegoldia, Anaerococcus, Sneathia, and Adlercreutzia) were lower in women with diabetes compared to those without diabetes (all P < .01). In women with diabetes, plasma levels of several metabolites in tryptophan catabolism (e,g., kynurenine/tryptophan ratio), branched-chain amino acid and proline metabolism pathways were higher, while glycerophospholipids were lower (all P < .05). Results were generally consistent between HIV-infected and HIV-uninfected women, and no significant modification effects by HIV serostatus were observed (all Pinteraction > 0.05). Anaerococcus, known to produce butyrate which is involved in anti-inflammation and glucose metabolism, showed an inverse correlation with kynurenine/tryptophan ratio (r = -0.38, P < .01). INTERPRETATION Among women with or at high risk for HIV infection, diabetes is associated with gut microbiota and plasma metabolite alteration, including depletion of butyrate-producing bacterial population along with higher tryptophan catabolism. FUND NHLBI (K01HL129892, R01HL140976) and FMF.
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Investigating the interaction between human immunodeficiency virus, nutrition, and disability: A cross-sectional observational study.
Myezwa, H, Hanass-Hancock, J, Pautz, N
African journal of primary health care & family medicine. 2018;(1):e1-e8
Abstract
The average lifespan of people with human immunodeficiency virus (HIV) has increased because of the enhanced access to anti-retroviral treatment. This increased longevity has led to a heightened focus on the comorbidities which may arise, allowing a clearer understanding of the contextual, personal, psychological and functional problems and their interrelations. Disability (functional limitations) and insufficient nutritional intake may interact cyclically with HIV and/or acquired immunodeficiency syndrome (AIDS); however, no research to date has investigated this interaction. Aims: The objective of this article was to report on the nutritional outcomes using albumin and body mass index outcomes as a subset of a larger study among adults living with HIV and/or AIDS. Setting: This study was conducted at a large HIV clinic based in an urban area in Johannesburg, South Africa, which provides HIV treatment and support to over 6000 persons with HIV and TB. This clinic is part of a large public health regional hospital where extensive HIV research is undertaken. Methods: This study was a cross-sectional observational study. The sample composed of 278 participants between 18 and 65 years of age and had been on highly active antiretroviral therapy (HAART) for more than six months. Statistical analyses were performed using the Statistical Package for the Social Sciences. Results: The results indicated that albumin level had significant inverse associations with functional limitations and physical health symptoms. Women were significantly more likely to have lower nutritional levels. A logistic regression analysis suggested that gender and physical health symptoms were the primary predictors of albumin levels. Conclusion: The findings presented in this article can be applied to HIV and/or AIDS treatment programmes, such as HAART. It re-emphasises the importance of providing individuals on anti-retroviral therapy with affordable and adequate nutrition, education on the importance of nutritional intake and the benefits of potentially adopting supplement programmes. As females seem to be more adversely affected by low nutritional levels, with the findings showing an increased likelihood of developing physical health symptoms, focus also needs to be given to cultural or social factors that impact nutritional intake in women.
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5.
Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial.
Mallewa, J, Szubert, AJ, Mugyenyi, P, Chidziva, E, Thomason, MJ, Chepkorir, P, Abongomera, G, Baleeta, K, Etyang, A, Warambwa, C, et al
The lancet. HIV. 2018;(5):e231-e240
Abstract
BACKGROUND In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. METHODS We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5-12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] <16-18 kg/m2 or BMI-for-age Z scores <-3 for children). We did the randomisation with computer-generated, sequentially numbered tables with different block sizes incorporated within an online database. Randomisation was stratified by centre, age, and two other factorial randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8, 12, 18, 24, 36, and 48, and included nurse assessment of vital status and symptoms and dispensing of all medication including ART and RUSF. The primary outcome was mortality at week 24, analysed by intention to treat. Secondary outcomes included absolute changes in weight, BMI, and mid-upper-arm circumference (MUAC). Safety was analysed in all randomly assigned participants. Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov (NCT01825031) and the ISRCTN registry (43622374). FINDINGS Between June 18, 2013, and April 10, 2015, we randomly assigned 1805 participants to treatment: 897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10·9%, 95% CI 9·0-13·1) participants allocated to RUSF and 92 (10·3%, 8·5-12·5) to no-RUSF died within 24 weeks (hazard ratio 1·05, 95% CI 0·79-1·40; log-rank p=0·75), with no evidence of interaction with the other randomisations (both p>0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). INTERPRETATION In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. FUNDING Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).
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Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals.
Mora-Peris, B, Bouliotis, G, Ranjababu, K, Clarke, A, Post, FA, Nelson, M, Burgess, L, Tiraboschi, J, Khoo, S, Taylor, S, et al
AIDS (London, England). 2018;(8):1007-1015
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Abstract
BACKGROUND Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed. RESULTS Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/μl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17). CONCLUSION Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.
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Gut microbial diversity in HIV infection post combined antiretroviral therapy: a key target for prevention of cardiovascular disease.
El-Far, M, Tremblay, CL
Current opinion in HIV and AIDS. 2018;(1):38-44
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Abstract
PURPOSE OF REVIEW Although the HIV-infected population is living longer and getting older under current treatment regimens, significant challenges arise for health management as the infection is associated with various premature aging phenotypes, particularly increased incidence of cardiovascular diseases (CVDs). Here we review the current understanding of HIV-related gut dysbiosis in association with CVD and advances in clinical trials aiming to restore gut microbial diversity. RECENT FINDING Identification of a unique signature for gut dysbiosis in HIV infection between different cohorts remains challenging. However, low diversity of microbiota combined with the outgrowth of pathogenic bacterial species together with dysregulated metabolic pathways have been linked to compromised gut immunity, bacterial translocation and systemic inflammation, hence higher CVD risk among different cohorts. Data from recent clinical trials aiming to evaluate the tolerability and efficacy of probiotics in treated HIV+ patients are promising and support a significant increase in microbiota diversity and reduction of systemic inflammation. However, the impact of these microbial and immunological corrections on the prevalence of CVD in HIV+ patients remains unclear. SUMMARY Positive immunological outcomes following enrichment of the gut microbial diversity have been documented, and further trials are in progress to evaluate the range of patients, with different immunological backgrounds, who might benefit from these treatments.
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Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants.
Koay, WLA, Lindsey, JC, Uprety, P, Bwakura-Dangarembizi, M, Weinberg, A, Levin, MJ, Persaud, D
The Journal of infectious diseases. 2018;(7):1085-1089
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Abstract
Intestinal fatty acid binding protein (iFABP) levels did not differ between human immunodeficiency virus type 1 (HIV-1)- infected infants and uninfected infants exposed to HIV-1, but those who breastfed had substantially lower levels. Zonulin levels increased from 3 to 5.3 months of age with perinatal acquisition of HIV-1 despite early antiretroviral treatment. Biomarkers of intestinal integrity (ie, iFABP and zonulin) were compared in 56 HIV-1-positive African infants who received early antiretroviral treatment and 53 HIV-1-exposed but uninfected (HEU) controls. Despite heightened inflammation and immune activation in HIV-positive infants, iFABP and zonulin levels at 3 months of age were not different from those in HEU infants and largely were not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased and became significantly higher in HIV-positive infants as compared to HEU infants by 5 months of age, despite viral suppression due to antiretroviral treatment. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.
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Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial.
Kityo, C, Szubert, AJ, Siika, A, Heyderman, R, Bwakura-Dangarembizi, M, Lugemwa, A, Mwaringa, S, Griffiths, A, Nkanya, I, Kabahenda, S, et al
PLoS medicine. 2018;(12):e1002706
Abstract
BACKGROUND In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. METHODS AND FINDINGS In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) <100 cells/mm3, from eight urban/peri-urban HIV clinics at regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe were randomised 1:1 to initiate standard triple-drug ART, with or without 12-week raltegravir intensification, and followed for 48 weeks. The primary outcome was 24-week mortality, analysed by intention to treat. Of 2,356 individuals screened for eligibility, 1,805 were randomised between 18 June 2013 and 10 April 2015. Of the 1,805 participants, 961 (53.2%) were male, 72 (4.0%) were children/adolescents, median age was 36 years, CD4 count was 37 cells/mm3, and plasma viraemia was 249,770 copies/mL. Fifty-six participants (3.1%) were lost to follow-up at 48 weeks. By 24 weeks, 97/902 (10.9%) raltegravir-intensified ART versus 91/903 (10.2%) standard ART participants had died (adjusted hazard ratio [aHR] = 1.10 [95% CI 0.82-1.46], p = 0.53), with no evidence of interaction with other randomisations (pheterogeneity > 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76-1.28], p = 0.91); in serious (aHR = 0.99 [0.81-1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71-1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63-1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76-1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. CONCLUSIONS Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. TRIAL REGISTRATION ClinicalTrials.gov NCT01825031. TRIAL REGISTRATION International Standard Randomised Controlled Trials Number ISRCTN 43622374.
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Effect of a Structured Pharmaceutical Care Intervention Versus Usual Care on Cardiovascular Risk in HIV Patients on Antiretroviral Therapy: INFAMERICA Study.
Morillo-Verdugo, R, Robustillo-Cortés, MLA, Martín-Conde, MT, Callejón-Callejón, G, Cid-Silva, P, Moriel-Sánchez, C, Tortajada-Goitia, B, Almeida-González, CV
The Annals of pharmacotherapy. 2018;(11):1098-1108
Abstract
BACKGROUND HIV+ patients have increased their life expectancy with a parallel increase in age-associated comorbidities. OBJECTIVE To determine the effectiveness of an intensive pharmaceutical care follow-up program in comparison to a traditional model among HIV-infected patients with moderate/high cardiovascular risk. METHOD This was a multicenter, prospective, randomized study of a structured health intervention conducted between January-2014 and June-2015 with 12 months of follow-up at outpatient pharmacy services. The selected patients were randomized to a control group (usual care) or intervention group (intensive pharmaceutical care). The interventional program included follow-up of all medication taken by the patient to detect and work toward the achievement of pharmacotherapeutic objectives related to cardiovascular risk and making recommendations for improving diet, exercising, and smoking cessation. Individual motivational interview and periodic contact by text messages about health promotion were used. The primary end point was the percentage of patients who had reduced the cardiovascular risk index, according to the Framingham-score. RESULTS A total of 53 patients were included. As regards the main variable, 20.7% of patients reduced their Framingham-score from high/very high to moderate/low cardiovascular risk versus 12.5% in the control group ( P=0.016). In the intervention group, the number of patients with controlled blood pressure increased by 32.1% ( P=0.012); 37.9% of patients overall stopped smoking ( P=0.001), and concomitant medication adherence increased by 39.4% at the 48-week follow-up ( P=0.002). Conclusion and Relevance: Tailored pharmaceutical care based on risk stratification, motivational interviewing, and new technologies might lead to improved health outcomes in HIV+ patients at greater cardiovascular risk.