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1.
Impact of HIV and antiretroviral drug exposure on lung growth and function over 2 years in an African Birth Cohort.
Gray, DM, Wedderburn, CJ, MacGinty, RP, McMillan, L, Jacobs, C, Stadler, JAM, Hall, GL, Zar, HJ
AIDS (London, England). 2020;(4):549-558
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Abstract
OBJECTIVE To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. DESIGN Prospective observational study of an African birth cohort, Drakenstein Child Health Study. METHOD Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. RESULTS Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P = 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (-2.7 ml, -5.31 to -0.10, P = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (-11.1 ml, -18.58-3.58, P = 0.004). CONCLUSION HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.
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Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation.
Rentsch, KM
Therapeutic drug monitoring. 2020;(2):255-263
Abstract
The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.
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Women living with HIV in high-income settings and breastfeeding.
Moseholm, E, Weis, N
Journal of internal medicine. 2020;(1):19-31
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Abstract
Guidelines in high-income settings recommend breastfeeding avoidance amongst women living with HIV (WLWH). Increasingly, WLWH in high-income settings, who are well-treated with fully suppressed viral loads, are choosing to breastfeed their infants, even with these recommendations. The purpose of this article is to review existing research and guidance on infant feeding amongst WLWH in high-income countries and to identify gaps in this evidence that require further investigation. Current evidence on the risk of HIV transmission through breastfeeding in the context of antiretroviral therapy (ART), the significance of cell-associated virus, transmission risk factors, retention in care and adherence postpartum, infant prophylaxis and antiretroviral exposure, and monitoring of the breastfeeding WLWH are summarized. A latent HIV reservoir is persistently present in breast milk, even in the context of ART. Thus, suppressive maternal ART significantly reduces, but does not eliminate, the risk of postnatal transmission of HIV. There are currently limited data to guide the optimal frequency of virologic monitoring and the clinical actions to take in case of maternal detectable viral load whilst breastfeeding. Moreover, retention in care and adherence to ART in the postpartum period may be difficult and more research is needed to understand what clinical and psychosocial support would benefit these mothers so that successful engagement in care can be achieved. The long-term effects of antiretroviral drug exposure in the infants also need further exploration. Thus, there is a need for collecting enhanced surveillance data on WLWH who breastfeed and their infants to augment clinical guidance in high-income settings.
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FGF21 and its Relationship with Inflammatory and Metabolic Parameters in HIV Patients after Antiretroviral Treatment.
Ruiz-Padilla, AJ, Ruiz-Noa, Y, Del Rocio Ibarra-Reynoso, L, Lazo-de-la-Vega-Monroy, ML, Alonso-Castro, AJ, Sánchez-Barajas, M, Alvarez-Alvarez, RM, Del Carmen Preciado-Puga, M
Current HIV research. 2020;(5):308-314
Abstract
BACKGROUND Fibroblast Growth Factor 21 (FGF21) serum levels are associated with insulin resistance and metabolic syndrome in HIV patients. OBJECTIVE To quantify FGF21 levels in HIV patients using antiretroviral therapy (ART) and to analyze a possible association between serum FGF21 levels and lipid profile, levels of proinflammatory cytokines, and atherogenic risk factors. MATERIALS AND METHODS Twenty patients with HIV infection, who received ART in a scheme consisting of Tenofovir/Emtricitabine+Lopinavir/Ritonavir, were enrolled in this study. The serum levels of FGF21, inflammatory parameters (IL-6 and IL-1β), glucose, cholesterol, triglycerides, and insulin were determined at baseline and after 36 weeks of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) and the atherogenic risk factor were also calculated. RESULTS After 36 weeks, serum FGF21 levels decreased significantly (p=0.011), whereas IL-6 levels (r=0.821, p=0.0001) and the CD4+ T cell count (r=0.446, p=0.048), showed a positive correlation with the decrease in FGF21 levels. There was an increase in total cholesterol (r=-0.483, p=0.031), LDL (r=-0.496, p=0.026), VLDL (r=-0.320, p=0.045), and the atherogenic index factor (r=-0.539, p=0.014), these values showed a negative correlation with FGF21 levels. CONCLUSION The decrease of serum FGF21 levels due to ART is associated with the alteration in lipid profile and an increased risk for cardiovascular diseases. These variations are predictors of inflammatory status in HIV patients using antiretroviral therapy.
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Co-medications and Drug-Drug Interactions in People Living with HIV in Turkey in the Era of Integrase Inhibitors.
Yeşilbağ, Z, Şengül, Eİ, Şenoğlu, S, Aydın, ÖA, Karaosmanoğlu, HK
Current HIV research. 2020;(6):415-425
Abstract
BACKGROUND Long life expectancy in people living with human immunodeficiency virus (PLWH) caused an increase in comorbidities and co-medications. We aimed to analyse comedications and drug-drug interactions (DDIs) in antiretroviral therapy (ART)-naive PLWH in the era of integrase inhibitors. METHODS A retrospective observational study was conducted between January 2016-August 2019. Patients' characteristics and chronic co-medications were recorded. The University of Liverpool HIV drug interaction database was used for DDIs. RESULTS Among 745 patients, the chronic co-medication rate was 30.9%. Older age (p<0.001, OR:6.66, 95% CI: 3.86-11.49) and female gender (p=002, OR:2.25, 95%:1.14-4.44) were independently associated with co-medication. Cardiovascular system (CVS) and central nervous system (CNS) drugs were the most common co-medications. Older age patients (p<0.001, OR:12.04, 95% CI:4.63-36.71), having heterosexual (HS) contact (p=0.003, OR:3.8, 95% CI:1.57-9.22) were independently associated with CVS drugs use, while being men who have sex with men (MSM) (p=0.03, OR:2.59, 95% CI:1.11-6.03) were associated with CNS drugs use. DDIs were seen in 37.4% of patients with co-medications. Antidiabetics (23.3%), CNS (22.1%) and CVS drugs (19.8%) most commonly had DDIs. Contraindication was most commonly seen between inhaled corticosteroids and elvitegravir/cobicistat. A number of non-ART drugs, elvitegravir/cobicistat, antidiabetics, vitamins were independently associated with the presence of DDIs. CONCLUSION Results suggested the need for attention about co-medication in PLWH regardless of whether they are young or older. CNS drugs should be questioned more detailed in MSM, as well as CVS drugs in older HS patients. Elvitegravir/cobicistat is significantly associated with DDIs and switching to an unboosted INSTI should be considered in patients with multiple comorbidities.
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Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV.
Gonçalves, JL, Silva, MCA, Roma, EH, Grinsztejn, B, Lemos, ADS, Gorni, N, Cruz, AM, Almeida, CF, Quintana, MSB, Bonecini-Almeida, MDG, et al
Memorias do Instituto Oswaldo Cruz. 2020;:e190350
Abstract
BACKGROUND Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.
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Management of oral antiretroviral administration in patients with swallowing disorders or with an enteral feeding tube.
San, C, Lê, MP, Matheron, S, Mourvillier, B, Caseris, M, Timsit, JF, Wolff, M, Yazdanpanah, Y, Descamps, D, Peytavin, G
Medecine et maladies infectieuses. 2020;(7):537-544
Abstract
HIV infection has evolved into a chronic disease with comorbidities since the combination antiretroviral therapy era. Complications still occur and patients may need to be admitted to an intensive care unit. Acute respiratory failure is the first cause of these admissions, questioning the administration of solid oral dosage formulations. This issue is also observed in geriatric units where the prevalence of dysphagia is high and underestimated. The problem of antiretroviral administration is critical: altered solid oral dosage formulations and/or administration via enteral feeding tubes are sometimes the only option. The aim is to help manage antiretroviral treatment in unconscious or intubated patients and those with swallowing disorders who are hospitalized in intensive care units or geriatric units. This review provides information on the main antiretroviral regimens and on practical and legal aspects of manipulating solid oral dosage formulations and administration via enteral feeding tubes. Alternatives to the solid formulation are available for most of the 27 oral antiretrovirals available, or manufacturers provide recommendations for patients who are unable to swallow. Manipulation of solid oral dosage formulations such as crushing tablets or opening capsules and administration via feeding tubes are frequently reported but should be the last option for safety and liability issues. Before any off-label administration of a drug, physicians should consider alternatives to the solid oral dosage formulation and check whether the drug can be altered. Therapeutic monitoring is important in this particular setting as the pharmacokinetic profile of drugs is difficult to predict.
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The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection.
Alvarez, N, Aguilar-Jimenez, W, Rugeles, MT
Frontiers in immunology. 2019;:2291
Abstract
HIV infection remains a global and public health issue with the incidence increasing in some countries. Despite the fact that combination antiretroviral therapy (cART) has decreased mortality and increased the life expectancy of HIV-infected individuals, non-AIDS conditions, mainly those associated with a persistent inflammatory state, have emerged as important causes of morbidity, and mortality despite effective antiviral therapy. One of the most common comorbidities in HIV-1 patients is Vitamin D (VitD) insufficiency, as VitD is a hormone that, in addition to its physiological role in mineral metabolism, has pleiotropic effects on immune regulation. Several reports have shown that VitD levels decrease during HIV disease progression and correlate with decreased survival rates, highlighting the importance of VitD supplementation during infection. An extensive review of 29 clinical studies of VitD supplementation in HIV-infected patients showed that regardless of cART, when VitD levels were increased to normal ranges, there was a decrease in inflammation, markers associated with bone turnover, and the risk of secondary hyperparathyroidism while the anti-bacterial response was increased. Additionally, in 3 of 7 studies, VitD supplementation led to an increase in CD4+ T cell count, although its effect on viral load was inconclusive since most patients were on cART. Similarly, previous evidence from our laboratory has shown that VitD can reduce the infection of CD4+ T cells in vitro. The effect of VitD supplementation on other HIV-associated conditions, such as cardiovascular diseases, dyslipidemia or hypertension, warrants further exploration. Currently, the available evidence suggests that there is a potential role for VitD supplementation in people living with HIV-1, however, comprehensive studies are required to define an adequate supplementation protocol for these individuals.
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Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study.
Hompe, ED, Jacobson, DL, Eudailey, JA, Butler, K, Edwards, W, Pollara, J, Brummel, SS, Fouda, GG, Chinula, L, Kamanga, M, et al
mSphere. 2019;(5)
Abstract
To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibody-dependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk.IMPORTANCE Each year, >150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.
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Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohort (SCOLTA).
Taramasso, L, Ricci, E, Cascio, A, Valsecchi, L, Menzaghi, B, Squillace, N, Maggi, P, De Socio, GV, Dentone, C, Madeddu, G, et al
AIDS research and therapy. 2019;(1):21
Abstract
BACKGROUND Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. METHODS Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. RESULTS A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13-20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. CONCLUSIONS DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.