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1.
Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment.
Lagathu, C, Béréziat, V, Gorwood, J, Fellahi, S, Bastard, JP, Vigouroux, C, Boccara, F, Capeau, J
Expert opinion on drug safety. 2019;(9):829-840
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Abstract
Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.
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Current Strategies for Elimination of HIV-1 Latent Reservoirs Using Chemical Compounds Targeting Host and Viral Factors.
Jean, MJ, Fiches, G, Hayashi, T, Zhu, J
AIDS research and human retroviruses. 2019;(1):1-24
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Abstract
Since the implementation of combination antiretroviral therapy (cART), rates of HIV type 1 (HIV-1) mortality, morbidity, and newly acquired infections have decreased dramatically. In fact, HIV-1-infected individuals under effective suppressive cART approach normal life span and quality of life. However, long-term therapy is required because the virus establish a reversible state of latency in memory CD4+ T cells. Two principle strategies, namely "shock and kill" approach and "block and lock" approach, are currently being investigated for the eradication of these HIV-1 latent reservoirs. Actually, both of these contrasting approaches are based on the use of small-molecule compounds to achieve the cure for HIV-1. In this review, we discuss the recent progress that has been made in designing and developing small-molecule compounds for both strategies.
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Health Characteristics Associated With Hot Flashes in Women With HIV During Menopause: An Integrative Review.
Rivard, C, Philpotts, LL, Flanagan, J, Looby, SE
The Journal of the Association of Nurses in AIDS Care : JANAC. 2019;(1):87-97
Abstract
Hot flashes (HFs) are a prominent symptom of menopause known to unfavorably influence mood, sleep, and quality of life. More women living with HIV are entering menopause and may experience a greater prevalence of HFs and more severe HFs compared with uninfected women. This integrative review evaluated existing evidence on potential health characteristics associated with HFs in women living with HIV during menopause. A search strategy was conducted within 6 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guided the review, and the Johns Hopkins Nursing Evidence-Based Practice model was used to evaluate methodological quality and appraisal of the evidence. Five articles met the review eligibility criteria. Three content categories emerged from the key findings of the 5 articles: HIV-specific characteristics, mental health and cognitive characteristics, and quality of life and social characteristics. Implications for research and clinical care were identified.
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Comorbid HIV infection and alcohol use disorders: Converging glutamatergic and dopaminergic mechanisms underlying neurocognitive dysfunction.
Giacometti, LL, Barker, JM
Brain research. 2019;:146390
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Abstract
Alcohol use disorders (AUDs) are highly comorbid with human immunodeficiency virus (HIV) infection, occurring at nearly twice the rate in HIV positive individuals as in the general population. Individuals with HIV who consume alcohol show worse long-term prognoses and may be at elevated risk for the development of HIV-associated neurocognitive disorders. The direction of this relationship is unclear, and likely multifactorial. Chronic alcohol exposure and HIV infection independently promote cognitive dysfunction and further may interact to exacerbate neurocognitive deficits through effects on common targets, including corticostriatal glutamate and dopamine neurotransmission. Additionally, drug and alcohol use is likely to reduce treatment adherence, potentially resulting in accelerated disease progression and subsequent neurocognitive impairment. The development of neurocognitive impairments may further reduce cognitive control over behavior, resulting in escalating alcohol use. This review will examine the complex relationship between HIV infection and alcohol use, highlighting impacts on dopamine and glutamate systems by which alcohol use and HIV act independently and in tandem to alter corticostriatal circuit structure and function to dysregulate cognitive function.
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Transmission of CMV, HTLV-1, and HIV through breastmilk.
Prendergast, AJ, Goga, AE, Waitt, C, Gessain, A, Taylor, GP, Rollins, N, Abrams, EJ, Lyall, EH, de Perre, PV
The Lancet. Child & adolescent health. 2019;(4):264-273
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Abstract
Breastfeeding is a crucial child survival intervention. However, the potential for transmission of viral infections from mother to child presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. In this Review, we compare the transmission dynamics, risk factors, and outcomes of infection with three chronic viruses transmitted through breastmilk: cytomegalovirus, human T-cell lymphotropic virus type 1, and HIV. We provide an overview of intervention approaches and discuss scientific, policy, and programming gaps in the understanding of these major global infections.
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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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Erythema elevatum diutinum: a case report and review of literature.
Doktor, V, Hadi, A, Hadi, A, Phelps, R, Goodheart, H
International journal of dermatology. 2019;(4):408-415
Abstract
Erythema elevatum diutinum (EED) is a rare cutaneous leukocytoclastic vasculitis thought to be related to increased levels of circulating antibodies. It has been shown to be associated with HIV infection, tuberculosis, as well as various autoimmune diseases. A retrospective review of all cases of EED indexed in PubMed between 1990 and 2014 was performed. Inclusion criteria for articles was availability of full text in English and a biopsy-confirmed diagnosis of EED. All other articles were excluded. Cases were stratified by age and anatomic location of the lesions. Treatment response was coded as "complete," "partial," and "none." A total of 133 cases of EED with 381 lesions detailed in case reports and case series were included. Twenty-one cases were associated with HIV. Of 47 patients with reported paraproteinemias, IgA paraproteinemia was found in 57.45%, IgG paraproteinemia in 29.8%, IgM paraproteinemia in 10.6%, and IgD paraproteinemia in 2.1% of cases. Of 40 (30.1%) patients with reported comorbid autoimmune disease, rheumatoid arthritis was associated with 10 cases. Cancer was found to be associated with 9.77% of cases. Seventy-five patients were treated with dapsone, with 36 (48%) achieving complete treatment response, 24 (32%) achieving partial response, and seven (9.3%) achieving no response. Keeping the clinical associations of EED in mind, especially malignancy, is critical in management of the disease. More structured studies need to take place in order to fully define the mechanisms and strength of these associations.
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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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Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors.
Yang, LL, Li, Q, Zhou, LB, Chen, SQ
International journal of antimicrobial agents. 2019;(5):547-555
Abstract
Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. A meta-analysis of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients was performed. Odds ratios (ORs) of efficacy outcome data favouring INSTI use in different clinical settings demonstrated that INSTIs have higher efficacy compared with drugs of other classes. For combination antiretroviral therapy-naïve patients and virologically-suppressed patients who switched to INSTI-based therapy, the OR was 1.484 (95% CI 1.229-1.790) and 1.341 (95% CI 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virological failure than to non-INSTIs (OR = 0.081, 95% CI 0.004-1.849), whereas the opposite was observed for raltegravir (RAL) (OR = 3.137, 95% CI 1.827-5.385) and elvitegravir (EVG) (OR = 1.886, 95% CI 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir was rare, whereas EVG and RAL had low genetic barriers to resistance and the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring the emergence of resistance to INSTIs and the development of drugs with high genetic barriers are clear paths for future research.
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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.