Optimal antiretroviral therapy for aging

Sexual Health ◽  
2011 ◽  
Vol 8 (4) ◽  
pp. 534 ◽  
Author(s):  
Damien V. Cordery ◽  
David A. Cooper

The introduction of highly active antiretroviral therapy (HAART) has irrevocably changed the nature of the HIV epidemic in developed countries. Although the use of HAART does not completely restore health in HIV-infected individuals, it has dramatically reduced morbidity and mortality. Increases in life expectancy resulting from effective long-term treatment mean that the proportion of older people living with HIV has increased substantially in the past 15 years. Increasing age is associated with many complications including cardiovascular disease, neurological complications, kidney and liver dysfunction, and metabolic complications such as dyslipidaemia and diabetes. HIV infection and antiretroviral drugs have also been associated with similar complications to those seen with increasing age. The increase in HIV prevalence in older age groups has not been accompanied by the development of treatment guidelines or recommendations for appropriate antiretroviral therapy or clinical management in these patients.

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajpushpa Labh ◽  
Rachna Gupta

: Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of People Living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in fight against HIV. Few long acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, longacting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. LongActing Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 578
Author(s):  
Win-Long Lu ◽  
Yuan-Ti Lee ◽  
Gwo-Tarng Sheu

Treatment of HIV infection is a lifelong process and associated with chronic diseases. We evaluated the prevalence and predictors of metabolic syndrome (MetS) and cardiovascular diseases (CVDs) with individual antiretroviral drugs exposure among HIV-infected men in Taiwan. A total of 200 patients’ data were collected with a mean age of 32.9. Among them, those who had CD4 positive cell number less than 350/mL were eligible to have highly active antiretroviral therapy (HAART). Patients were divided into group-1 that contains 45 treatment-naïve participants, and group-2 that includes 155 HAART treatment-experienced participants. MetS prevalence between group-1 and group-2 was 18% and 31%, respectively. The Framingham Risk Score (FRS) for the naïve and experienced groups were 4.7 ± 4.2 and 3.87 ± 5.92, respectively. High triglyceride (TG > 150 mg/dL) in group-1 and group-2 were 15.6% and 36.6% (p < 0.05), whereas, lower high-density lipoprotein (HDL < 39 mg/dL) in group-1 and group-2 presented as 76.7% versus 51% (p < 0.05), respectively. In group-2, treatment with protease inhibitors (PIs) resulted in higher TG levels when compared with non-nucleotide reverse transcriptase inhibitors (NNRTIs) and integrase inhibitors (InSTIs). The prevalence of MetS in the treatment-naïve group was lower than that of the treatment-experienced group; high TG level resulted in higher MetS prevalence in the treatment-experienced group. In contrast, the cardiovascular risk of FRS in the treatment-naïve group was higher than that of the treatment-experienced group, which may result from the low HDL level. Although group-1 participants have a higher risk of developing CVDs, in group-2, an increasing TG level in PIs user indicated higher CVDs risk. TG and HDL are two significant biofactors that required regular evaluation in HIV-positive individuals.


2010 ◽  
Vol 84 (20) ◽  
pp. 10765-10772 ◽  
Author(s):  
Nonhlanhla N. Mkhize ◽  
Pamela P. Gumbi ◽  
Lenine J. Liebenberg ◽  
Yuan Ren ◽  
Peter Smith ◽  
...  

ABSTRACT Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.


2020 ◽  
Author(s):  
Abere Woretaw Azagew ◽  
Chilot Kassa Mekonnen ◽  
Abebaw Jember Ferede ◽  
Kassahun Gebeyehu Yazew ◽  
Zewdu Baye Tezera

Abstract Background: Adherence to highly active antiretroviral therapy (HAART) is a public health challenge worldwide. Non-adherence to HAART leads to treatment, immunologic, and virological failure. Despite different interventions made, adherence to HAART among adult people living with HIV (PLWHIV) is still inconsistent across studies, and the effect of serostatus disclosure on adherence to HAART was not studied in Ethiopia. Therefore, the study is aimed to determine the pooled prevalence of adherence to HAART and its relationship with serostatus disclosure among adult PLWHIV in Ethiopia.Methods: We searched 3247 original articles, both published and unpublished on Ethiopia dated from January 2016 to November 2019 by using different search engines. Data were extracted using Microsoft excel. New Castle Ottawa Scale quality assessment tool was used. STATA software version 11 was used for analysis. A random-effects model for meta-analysis was computed. Cochran Q statistics and I2 were used to estimate heterogeneity. Egger’s and Begg’s test was used to assess the publication bias.Results: A total of fifteen articles for systematic review and four articles for meta-analysis were used. The pooled prevalence of adherence to HAART is found to be 81.19% (80.1, 82.3). In the subgroup analysis, the pooled prevalence of adherence to HAART was 79.82% (73.19, 86.45) in the Oromia region, 82.51 %( 73.14, 91.87) in the Amhara region, and 72.7% (63.78, 81.61) in the Southern Nations Nationalities and Peoples’ Region (SNNPR). The serostatus disclosure improves adherence to HAART by nearly three times compared to non-serostatus disclosed PLWHIV (AOR=2.99, 95 %CI: 1.88, 4.77).Conclusions: The pooled prevalence of adherence to HAART among adult PLWHIV in Ethiopia was found to be low compared to WHO antiretroviral treatment recommendations. Having serostatus disclosure improved adherence to HAART.


2018 ◽  
Vol 9 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Swatantra Kumar ◽  
Vimal K Maurya ◽  
Himanshu R Dandu ◽  
Madan LB Bhatt ◽  
Shailendra K Saxena

AbstractAmong Human immunodeficiency virus (HIV) infected individuals, around two-thirds of patients present with neuroAIDS, where HIV-associated neurocognitive disorders (HAND), and HIV-associated dementia (HAD) are the most prevailing neurological complications. The neuropathology of neuroAIDS can be characterized by the presence of HIV infected macrophages and microglia in the brain, with the formation of multinucleated giant cells. Global predominant subtypes of HIV-1 clade B and C infections influence the differential effect of immune and neuronal dysfunctions, leading to clade-specific clinical variation in neuroAIDS patient cohorts. Highly active antiretroviral therapy (HAART) enhances the survival rate among AIDS patients, but due to the inability to cross the Blood-Brain-Barrier (BBB), incidence of neuroAIDS during disease progression may be envisaged. The complex structure of blood-brain-barrier, and poor pharmacokinetic profile coupled with weak bio-distribution of antiretroviral drugs, are the principle barriers for the treatment of neuroAIDS. In the combined antiretroviral therapy (cART) era, the frequency of HAD has decreased; however the incidence of asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorder (MND) remains consistent. Therefore, several effective novel nanotechnology based therapeutic approaches have been developed to improve the availability of antiretroviral drugs in the brain for the management of neuroAIDS.


Author(s):  
Jennifer Jao ◽  
Lauren C Balmert ◽  
Shan Sun ◽  
Grace A McComsey ◽  
Todd T Brown ◽  
...  

Abstract Context Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. Objective We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Methods Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Results Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. Conclusion Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.


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