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Neurological development of children who are HIV-exposed and uninfected.
Toledo, G, Côté, HCF, Adler, C, Thorne, C, Goetghebuer, T
Developmental medicine and child neurology. 2021;(10):1161-1170
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Abstract
Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV-uninfected, the increasing number of children who are HIV-exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV-specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long-term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes. What this paper adds Evidence on the neurological development of children who are human immunodeficiency virus (HIV)-exposed and uninfected (CHEU) is synthesized. Comparisons are made to children who are HIV-unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes. CHEU exposures are complex and include HIV-specific and universal risk factors which may affect development during the early years of life.
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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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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 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.
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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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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 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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Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence.
Willig, AL, Overton, ET
Current HIV/AIDS reports. 2016;(5):289-96
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HIV infection and antiretroviral therapy (ART) use are associated with perturbations in glucose and lipid metabolism. Increasing incidence of diabetes, cardiovascular disease, and obesity highlights the need for early identification and treatment of metabolic dysfunction. Newer ART regimens are less toxic for cellular function and metabolism but have failed to completely eliminate metabolic dysfunction with HIV infection. Additional factors, including viral-host interactions, diet, physical activity, non-ART medications, and aging may further contribute to metabolic disease risk in the HIV setting. We summarize the recent literature regarding the impact on metabolic function of HIV infection, ART, and pharmaceutical or lifestyle prescriptions.
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Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection.
Hunt, PW, Lee, SA, Siedner, MJ
The Journal of infectious diseases. 2016;(Suppl 2):S44-50
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Despite marked improvements in the modern treatment era, human immunodeficiency virus (HIV)-infected individuals, particularly those who initiated antiretroviral therapy (ART) at advanced disease stages, continue to have increased age-related morbidity and mortality, compared with the general population. Immune activation and inflammation persist despite suppressive ART and predict many of these morbidities. The goal of this review is to examine the evidence suggesting a link between the persistent inflammatory state and morbidity and mortality in this setting, to describe the impact of early ART initiation on these factors, and to highlight important unanswered questions for the field. We also advance a hypothesis to explain why some morbidities-and their root inflammatory drivers-may be prevented more than others by early ART initiation.
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Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials.
Jiang, J, Xu, X, Guo, W, Su, J, Huang, J, Liang, B, Chen, H, Zang, N, Liao, Y, Ye, L, et al
AIDS research and therapy. 2016;(1):30
Abstract
BACKGROUND The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. METHODS PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. RESULTS Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03-1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06, 95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.
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Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.
Borges, ÁH, Lundh, A, Tendal, B, Bartlett, JA, Clumeck, N, Costagliola, D, Daar, ES, Echeverría, P, Gisslén, M, Huedo-Medina, TB, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016;(2):268-80
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BACKGROUND Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. METHODS We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. RESULTS We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). CONCLUSIONS We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.