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Factors associated with antiretroviral therapy adherence in adults: an integrative review of literature.
Carvalho, PP, Barroso, SM, Coelho, HC, Penaforte, FRO
Ciencia & saude coletiva. 2019;(7):2543-2555
Abstract
AIDS is an advanced clinical manifestation of HIV infection. It generates severe immunodeficiency and associated infections that may lead to death. The antiretroviral therapy (ART) has reduced the morbimortality of HIV/AIDS, but its benefits depend on ART adherence. This integrative review followed the PICO method to identify factors associated with adult adherence to ART. Empirical papers published between January 2010 and December 2016 in the Medline, SciELO, Lilacs and PePSIC databases were included. We analyzed 125 papers regarding the characteristics of studies, adherence measures and associated factors. Results showed a wide variety in the definition of adherence and the use of measures for its monitoring, as well as several adherence-associated factors. These were categorized as follows: 1- Individual variables; 2- Treatment characteristics; 3- HIV/aids infection characteristics; 4- Relationship with the health services; 5- Social support. Health services should characterize the users' profiles, systematize adherence measures and regionally assess adherence-associated factors for the early detection of non-adherence to ART and implementation of effective intervention plans.
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Pre-exposure prophylaxis for HIV prevention during pregnancy and lactation: forget not the women and children.
Horgan, L, Blyth, CC, Bowen, AC, Nolan, DA, McLean-Tooke, AP
The Medical journal of Australia. 2019;(6):281-284
Abstract
Pregnancy is known to be a time of increased susceptibility to acquiring to human immunodeficiency virus (HIV) infection and this increased maternal risk places the unborn child at risk of vertical transmission. Pre-exposure prophylaxis (PrEP) involves the provision of antiretroviral therapy to an HIV-negative individual with ongoing risk of HIV exposure to limit the likelihood of HIV transmission. The inclusion of PrEP as part of a comprehensive strategy is recognised as an effective and safe means of reducing HIV infection in serodiscordant couples, thereby reducing the risk of vertical transmission of HIV. Current data suggest that PrEP is safe to continue during pregnancy and breastfeeding in HIV-negative women who remain vulnerable to acquiring HIV. The recent Pharmaceutical Benefits Scheme subsidisation of PrEP has reduced the financial and practical obstacles of PrEP provision, and a subsequent increase in patient awareness and acceptance of PrEP is expected. The framework for appropriately identifying and managing at-risk pregnant and lactating women requiring PrEP is poorly defined and warrants further clarification to better support clinicians and this patient group. This review discusses the current recommendations highlighting the gaps in the guidelines and makes some recommendations for future guideline development.
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Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV.
Hodel, EM, Marzolini, C, Waitt, C, Rakhmanina, N
Current pharmaceutical design. 2019;(5):556-576
Abstract
BACKGROUND Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants. METHODS We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively. RESULTS We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs. CONCLUSIONS Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter's role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.
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NCp7: targeting a multitask protein for next-generation anti-HIV drug development part 2. Noncovalent inhibitors and nucleic acid binders.
Iraci, N, Tabarrini, O, Santi, C, Sancineto, L
Drug discovery today. 2018;(3):687-695
Abstract
Nucleocapsid protein 7 (NCp7) represents a viable target not yet reached by the currently available antiretrovirals. It is a small and highly basic protein, which is essential for multiple stages of the viral replicative cycle, with its structure preserved in all viral strains, including clinical isolates. NCp7 can be inhibited covalently, noncovalently and by shielding the nucleic acid (NA) substrates of its chaperone activity. Although covalent NCp7 inhibitors have already been detailed in the first part of this review series, the focus here is based on noncovalent and NA-binder inhibitors and on the analysis of the NCp7 3D structure to deliver fruitful insights for future drug design strategies.
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Does U=U for breastfeeding mothers and infants? Breastfeeding by mothers on effective treatment for HIV infection in high-income settings.
Waitt, C, Low, N, Van de Perre, P, Lyons, F, Loutfy, M, Aebi-Popp, K
The lancet. HIV. 2018;(9):e531-e536
Abstract
Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice.
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Naturally occurring Vpr inhibitors from medicinal plants of Myanmar.
Win, NN, Ngwe, H, Abe, I, Morita, H
Journal of natural medicines. 2017;(4):579-589
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Abstract
Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.
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Renal effects of novel antiretroviral drugs.
Milburn, J, Jones, R, Levy, JB
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(3):434-439
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Abstract
Chronic kidney disease (CKD) is a critical comorbidity for patients living with HIV, with an estimated prevalence between 2.4 and 17%. Such patients are increasingly affected by diseases associated with ageing, including cardiovascular disease and CKD, and the prevalence of risk factors such as smoking and dyslipidaemia is increased in this population. Proteinuria is also now recognized as a common finding in individuals living with HIV. While combination antiretroviral (ARV) treatments reduce CKD in the HIV-infected population overall, some ARV drugs have been shown to be nephrotoxic and associated with worsening renal function. Over the last few years, several highly efficacious new ARV agents have been introduced. This brief review will look at the novel agents dolutegravir, raltegravir, elvitegravir, cobicistat, tenofovir alafenamide fumarate and atazanavir, all of which have been licensed relatively recently, and describe issues relevant to renal function, creatinine handling and potential nephrotoxicity. Given the prevalence of CKD, the wide range of possible interactions between HIV, ARV therapy, CKD and its treatments, nephrologists need to be aware of these newer agents and their possible effect on kidneys.
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Second- and Third-line Antiretroviral Therapy for Children and Adolescents: A Scoping Review.
Lazarus, E, Nicol, S, Frigati, L, Penazzato, M, Cotton, MF, Centeno-Tablante, E, Violari, A, Nicol, L
The Pediatric infectious disease journal. 2017;(5):492-499
Abstract
BACKGROUND The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. RESULTS The search retrieved 1982 records. Eighteen studies provided efficacy data: 1 randomized controlled trial, 7 phase II trials, 5 prospective and 5 retrospective cohorts. Five studies evaluated regimens in children failing first-line ART, 4 in children with multidrug resistance and 9 in children with variable treatment experience. Only 10/18 studies reported week 48 or month 12 outcomes. The overall proportion of children with virologic suppression defined by study at week 48 was 61.8%. Although the randomized controlled trial had low risk of bias, outcomes were similar between groups because of highly active optimized background regimens. All phase II and prospective studies were judged to have moderate to high risk of bias. No study compared currently recommended lopinavir-based second-line regimens for nonnucleoside reverse transcriptase inhibitor failures to other non-nonnucleoside reverse transcriptase inhibitor regimens head-to-head. CONCLUSIONS We found no evidence comparing current World Health Organization-recommended second- and third-line ART regimens with regimens including drugs of interest: raltegravir, darunavir, etravirine and atazanavir. Randomized controlled trials or prospective cohort studies with comparator arms, and bridging studies, ideally conducted in resource-limited settings, are required to guide future recommendations.
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Barriers to HIV remission research in low- and middle-income countries.
Rossouw, T, Tucker, JD, van Zyl, GU, Sikwesi, K, Godfrey, C
Journal of the International AIDS Society. 2017;(1):21521
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Abstract
INTRODUCTION HIV eradication and remission research has largely taken place in high-income countries. In low- and middle-income countries (LMIC), there may be factors that have a substantial impact on the size of the latent HIV reservoir and the immunological response to infection. If a curative strategy is to be available to all HIV-infected individuals, these factors must be understood. METHODS We use a scoping review to examine the literature on biological factors that may have an impact on HIV persistence in LMIC. Three databases were searched without date restrictions. RESULTS Uncontrolled viral replication and higher coinfection prevalence may alter the immunological milieu of individuals in LMIC and increase the size of the HIV reservoir. Differences in HIV subtype could also influence the measurement and size of the HIV reservoir. Immune activation may differ due to late presentation to care, presence of chronic infections, increased gut translocation of bacterial products and poor nutrition. CONCLUSIONS Research on HIV remission is urgently needed in LMIC. Research into chronic immune activation in resource poor environments, the immune response to infection, the mechanisms of HIV persistence and latency in different viral clades and the effect of the microbiological milieu must be performed. Geographic differences, which may be substantial and may delay access to curative strategies, should be identified.
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Renal manifestations of HIV during the antiretroviral era in South Africa: a systematic scoping review.
Assaram, S, Magula, NP, Mewa Kinoo, S, Mashamba-Thompson, TP
Systematic reviews. 2017;(1):200
Abstract
BACKGROUND It is estimated that 650,000 patients may develop human immunodeficiency virus (HIV)-related renal disease in South Africa. South Africa has recently adopted WHO policy, stipulating that all HIV-infected patients have access to antiretroviral treatment (ART) irrespective of CD4 cell count. METHODS We searched Google Scholar, PubMed, Medline, Cochrane Library, Worldcat.org and EBSCO host databases from July 2015 to December 2015. Eligibility criteria included articles pertaining to renal manifestations of HIV in South Africa from 2004 to 2015 in adult patients (≥ 18 years). We independently reviewed the articles for quality. Thematic content analysis was performed to identify patterns of renal manifestations from the included studies. The risk of bias (e.g. internal validity) in the included studies was evaluated using the mixed methods appraisal tool. RESULTS Eleven out 21 studies were eligible for data extraction. The prevalence of urine abnormalities on urine dipsticks was high but had poor sensitivity and specificity for detecting renal impairment. Normal renal function occurred in 28.4 to 79% of patients, mild renal impairment occurred in 19 to 57.1% and moderate renal impairment in 2 to 14.4%. Severe renal impairment occurred in 1.3% of patients. Both the Cockcroft-Gault equation (after correcting for bias) and the 4-variable Modification of Diet in Renal Disease equation (without the ethnicity factor for African Americans) have been validated for the estimation of glomerular filtration rate (eGFR) in Black South Africans. HIV-associated nephropathy was the most prevalent histology seen (57.2%). Older age, a lower CD4 count, a low haemoglobin and a detectable viral load were associated with renal impairment. Renal function improved in the first year of commencing ART as evidenced by the regression of proteinuria and the increase in eGFR. CONCLUSION The findings of the review have implications to the recently adopted 'test and treat' approach to HIV prevention and management. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016039270.