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1.
Prevention of Mother-to-Child Human Immunodeficiency Virus Transmission in Resource-Limited Countries.
Knapp, KM
Pediatric clinics of North America. 2022;(1):1-18
Abstract
The first pediatric AIDS cases were reported in 1982. A decade later, the World Health Organization estimated there were more than 500,000 pediatric AIDS cases resulting from mother-to-child transmission, 90% of which were in sub-Saharan Africa. Although the rate of new infections globally has been cut in half since the peak of the pandemic, human immunodeficiency virus (HIV) remains a public health threat, and rates of new infections continue to increase in some regions. Mother-to-child transmission of HIV has now been virtually eliminated in many parts of the world but remains an issue in resource-limited countries.
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2.
Inflammatory Myositis Secondary to Anti-Retroviral Therapy in a Child; Case Report and Review of the Literature.
Monaghan, M, Loh, C, Jones, S, Oware, A, Urankar, K, Roderick, M, Majumdar, A
Journal of neuromuscular diseases. 2021;(6):1089-1095
Abstract
Here, we describe a five year old girl with congenital HIV who had a six-week onset of rapidly deteriorating mobility and progressive proximal muscle weakness, associated with a raised Creatine Kinase (CK) level of 4330 U/L [25-200 U/L], subsequently diagnosed with an inflammatory myositis. Potential causes were investigated by paediatric neurology and immunology teams. Her viral load had been undetectable over the preceding two years, excluding a primary HIV myositis. While MRI scanning did not show evidence of definite myositis, a muscle biopsy showed evidence of an inflammatory process, comprising a moderate endomysial, perimysial and perivascular mononuclear (CD8 + T cell) infiltrate with increased MHC expression. No particular features of dermatomyositis or immune-mediated necrotising myopathy were identified and there were no features of an inclusion body myositis.Given the absence of active HIV infection, the role of anti-retroviral medications was considered. She had had a recent switch in medication, from twice daily Raltegravir (an Integrase Strand Transfer Inhibitor, INSTI) to once daily Dolutegravir (an INSTI) while continuing on an established daily protocol of Abacavir and Lamivudine (Nucleoside Reverse Transcriptase Inhibitors). Changing the Dolutegravir back to Raltegravir, in combination with continuing Lamivudine and Abacavir for two months made no difference to her weakness or CK levels. Moreover, this drug regimen had been well-tolerated over the preceding 19 month period. Changing the anti-retroviral regime completely to a single drug class (Protease Inhibitors) of Ritonavir and Darunavir, resulted in a dramatic improvement in her symptomatology. Within ten days she regained the ability to stand and walk, with a reduction in her CK from 1700 U/L at time of switch to 403 U/L [25-200]. This case highlights the potential risk of developing inflammatory myositis from anti-retrovirals even 19 months into treatment.
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3.
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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4.
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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5.
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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6.
Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities.
Nachman, S, Townsend, CL, Abrams, EJ, Archary, M, Capparelli, E, Clayden, P, Lockman, S, Jean-Philippe, P, Mayer, K, Mirochnick, M, et al
The lancet. HIV. 2019;(8):e552-e558
Abstract
Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10-19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.
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7.
Lipid Abnormalities in Persons Living With HIV Infection.
Waters, DD, Hsue, PY
The Canadian journal of cardiology. 2019;(3):249-259
Abstract
Lipid abnormalities are prevalent among persons living with HIV infection and contribute to increasing the risk of cardiovascular events. Antiretroviral therapy (ART) is associated with lipid abnormalities, most commonly hypertriglyceridemia, but also increases in low-density lipoprotein cholesterol and total cholesterol. Different classes of ART, and different drugs within classes, have differing effects on lipid levels, but in general newer drugs have more favourable effects compared with older ones. Low-level inflammation and chronic immune activation act on lipids through a variety of mechanisms to make them more atherogenic. As a consequence, risk is higher than would be expected for any given cholesterol level. Clinical outcome trials of cholesterol-lowering therapies have not yet been completed in people living with HIV, so that treatment decisions depend on extrapolation from studies in uninfected populations. Traditional risk assessment tools underestimate cardiovascular risk in individuals with HIV. Statins are the mainstay of lipid-lowering drug treatment; however, drug-drug interactions with ART must be considered. Simvastatin and lovastatin are contraindicated in patients taking protease inhibitors, and the dose of atorvastatin and rosuvastatin should be limited to 40 mg and 10 mg/d with some ART combinations. Switching from older forms of ART to lipid-friendly newer ones is a useful strategy as long as virologic suppression is maintained, but adding a statin lowers low-density lipoprotein cholesterol more effectively. Studies indicate that lipid abnormalities are not treated as aggressively in individuals living with HIV as they are in uninfected people, making this an opportunity to improve care.
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8.
Liver Disease in Human Immunodeficiency Virus Infection.
Oikonomou, KG, Tsai, E, Sarpel, D, Dieterich, DT
Clinics in liver disease. 2019;(2):309-329
Abstract
Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.
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9.
Treatment of Central Nervous System Manifestations of HIV in the Current Era.
Handoko, R, Spudich, S
Seminars in neurology. 2019;(3):391-398
Abstract
Treatment of neurological, neurocognitive, and neuropsychiatric impairment in the setting of human immunodeficiency virus (HIV) infection remains a complex problem, given several possible mechanisms of pathogenesis. The etiology must be determined based on clinical judgment and objective evidence, including cerebrospinal fluid (CSF) data from lumbar puncture and neuroimaging information from magnetic resonance imaging, when available and indicated. Other neuroinfectious etiologies must be ruled out, including central nervous system (CNS) opportunistic infections. HIV replication in the CNS (including CSF escape) should be evaluated for and excluded. If CSF HIV is detected, we recommend a treatment switch to antiretrovirals (ARVs) targeted to address any CSF HIV resistance mutations identified, or empiric treatment intensification using ARVs with high CNS penetration. If CSF HIV is not detected, treatment intensification with CCR5 inhibitors may be considered as an adjunct to reduce neuroinflammation. Finally, the current ARV regimen must be examined for possible neurotoxicity. Efavirenz has been well-recognized for its neuropsychiatric adverse effects and potential for causing sleep disturbances. Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV.
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10.
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.