Highly Active Antiretroviral Therapy Treatment Research Articles

Methanol Crude Peel Extract of P. granatum Prevents Oxidative Damage in Kidneys of Rats Exposed to Highly Active Antiretroviral Therapy.

Highly Active Antiretroviral Therapy (HAART) has been linked to oxidative damage to kidney cells leading to renal disease in people living with HIV/AIDS on HAART treatment. The toxic effects of HAART affect the patients' quality of life leading to poor adherence to their regimen. Therefore, the purpose of this study was to investigate the nephron-protective activity of methanol crude peel extract of Punica granatum (MPEPG) in HAART-administered Wistar rats. Thirty male albino Wistar rats weighing between 180-200g were randomly divided into six groups of five rats each. Group one served as normal control and was given distilled water only. Group two serves as a negative control and was given HAART at a dosage of 64 mg/kg. Groups 3 and 4 were given 100 and 400 mg/kg of MPEPG, respectively, while groups 5 and 6 were given MPEPG dosages of 100 and 400 mg/kg along with HAART, respectively, for 40 days. The rats were sacrificed under halothane anaesthesia, and the kidneys were removed for histological evaluation, while blood samples were analyzed for biochemical parameters. In the HAART (TLD) treated group, there was a significantly high amount of MDA and a lower level of the antioxidant enzymes SOD and CAT. Biochemical analysis revealed that animals treated with HAART (TLD) had significantly higher levels of urea and creatinine, which are biomarkers of kidney damage than the normal control animals. In contrast, all the kidney function markers were returned to normal levels in the HAART-treated group after administration of methanol crude peel extract of P. granatum. The kidney tissues of animals given HAART had considerable structural damage as revealed by histopathological studies. When HAART-exposed rats were treated with MPEPG, both the biochemical and histological results significantly improved. Methanol crude peel extract of P. granatum provided effective protection against kidney oxidative injury brought on by HAART because of its anti-oxidant and free radical scavenging properties.

Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein–Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV–BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient.

Comparison of retinochoroidal and optic nerve head microvascular circulation between HIV-positive patients and healthy subjects using optical coherence tomography angiography

To evaluate the retinal, choroidal, and optic disc head microvascular circulation in human immunodeficiency virus (HIV)-infected individuals without retinopathy receiving highly active antiretroviral therapy (HAART) using swept-source optical coherence tomography angiography (SS-OCTA). This cross-sectional study included 100eyes of 100patients with HIV infection but no HIV-related ocular disease and 108 eyes of 108 age- and sex-matched healthy subjects as the control group. SS-OCTA was used to assess foveal avascular zone (FAZ) area, retinal nerve fiber layer thickness (RNFL), choriocapillaris (CC) flow area, outer retinal (OR) thickness, radial peripapillary capillary (RPC) vessel density (VD), ONH VD, and choroidal thickness. No statistically significant difference was found between the two groups except in the foveal VD of the deep capillary plexus (DCP). The foveal VD of the DCP was lower in the HIV-positive group (P=0.011). The mean FAZ area (mm2), perimeter (mm), and CC flow area (mm) values were higher in the HIV-positive group at statistically significant levels (P=0.021, P=0.02, and P=0.039, respectively). However, no statistically significant differences were found between the two groups concerning the OR flow area, subfoveal choroidal thickness, or the VDs of the RPC or ONH. This is the first study in the literature to evaluate the microvascular circulation of the ONH in HIV-positive patients. Although retinal and choroidal microvascular circulation decreased in HIV-positive patients receiving HAART treatment, we found no effect on the microvascular circulation of the ONH or RPC microvascular circulation. Our findings suggest that retinochoroidal microvascular circulation is affected in HIV-positive patients over time.

Highly active antiretroviral therapy-related effects on morphological connectivity in HIV.

Suboptimal concentration of the antiretroviral drug is insufficient to inhibit HIV destruction on brain structure and function due to the resistance of blood brain barrier. We aimed to investigate highly active antiretroviral therapy (HAART)-related effects on the morphological connectivity in people with HIV (PWH). Case-control study. Fifty-five HAART-treated for more than 3 months and 54 untreated PWH, as well as 66 demographically matched healthy controls underwent a high-resolution 3D T1-weighted MRI. Individual-level morphological brain network based on gray matter volume of 90 brain regions was constructed and network topological properties were analyzed. Network-based statistics (NBS) was performed to identify sub-networks showing significant differences in morphological connectivity. Correlation and mediation analyses were employed to evaluate associations between the morphological properties and clinical variables of PWH. Although PWH exhibited small-world architecture in their morphological brain networks, untreated PWH demonstrated altered network properties while HAART-treated PWH showed relatively similar network properties compared to healthy controls. Furthermore, HAART-related effects were mainly involved the bilateral putamen and left thalamus. The findings of NBS further indicated the cortico-striatum-thalamic-cortical loop was involved in the therapeutic-associated morphological network. The positive correlations between the HAART treatment and nodal degree and efficiency of the putamen were mediated by the number of CD4 + T lymphocytes. The topological properties are recovered to normal in PWH after HAART and the effects induced by HAART are mostly within the cortical-subcortical circuit.

Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.

Highly active antiretroviral therapy (HAART) is an accepted treatment option for patients with virus infection. Mounting evidence indicated that persistent HAART treatment is implicated with increased morbidity of HIV-associated neurocognitive disorders (HAND) in patients. Tenofovir disoproxil fumarate (TDF), a novel nucleotide reverse transcriptase inhibitor (NRTI), was used in patients with HIV co-infected with HBV. And it is still a vital first-line antiretroviral compounds in HAART. However, whether persistent treatment with TDF is involved in HAND development remains to be further elucidated.In this study, we aimed to discuss the neurotoxicity of TDF. We used SH-SY5Y cells and primary neuronal cells to evaluate the neurotoxicity of TDF in vitro. The cytotoxicity of TDF on SH-SY5Y cells and primary neuronal cells was evaluated by the cell viability and LDH levels by MTT assay and LDH kit, respectively. Hoechst 33342 staining, TUNEL assay and flow cytometry were performed to evaluate the cells apoptosis. The intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production were measured by commercial kits. In addition, the activation level of caspase-3 was evaluated using spectrophotometry and western blotting. Our results showed that TDF treatment significantly induced cell viability and induced apoptosis of SH-SY5Y cells and primary neuronal cells. Furthermore, the ROS levels and MDA productions were significantly up-regulated in nerve cells treated with TDF. CONCLUSION: Our findings indicated that TDF may induce neuronal cell apoptosis through increasing the intracellular ROS and the expression level of caspase-3, which may be related to the increasing prevalence of HAND.

Effect of genetic variations in drug transporters, metabolizing enzyme and regulatory genes on the development of HIV-associated lipodystrophy.

Adipocytes play a crucial role in the metabolism of lipids and sugars. Their response varies depending on the circumstances or other factors influenced by physiological and metabolic stresses. People living with HIV (PLWH) experience different effects of HIV and highly active antiretroviral therapy (HAART) on their body fat. Some patients respond well to antiretroviral therapy (ART), while others taking similar regimens do not. The genetic makeup of patients has been strongly linked to the variable responses to HAART among PLWH. The cause of HIV-associated lipodystrophy syndrome (HALS) is not well understood, but it may be influenced by genetic variations in the host. The metabolism of lipid effectively modulates plasma triglyceride and high-density lipoprotein cholesterol levels in PLWH. Genes related to drug metabolism and transport play an important role in the transportation and metabolism of ART drugs. Genetic variation in metabolizing enzyme genes of antiretroviral drugs, lipid transport and transcription factor-related genes could interfere with fat storage and metabolism, contributing to the development of HALS. Hence we examined the impact of genes associated with transport, metabolism and various transcription factors in metabolic complications, and their impact on HALS. A study using databases such as PubMed, EMBASE and Google Scholar was conducted to understand the impact of these genes on metabolic complications and HALS. The present article discuss the changes in the expression and regulation of genes and their involvement in the lipid metabolism, lipolysis and lipogenesis pathways. Moreover, alteration of the drug transporter, metabolizing enzyme and various transcription factors can lead to HALS. Single-nucleotide polymorphisms in genes that play an essential role in drug metabolism and drug and lipid transportation may also contribute to individual differences in the emergence of metabolic and morphological alterations during HAART treatment.

Nutritional status and effect of highly active anti-retroviral therapy (HAART) on selected trace elements in people living with HIV in Ghana

Background and objectivesEssential trace elements obtained from our diet are crucial for the initiation and development of host defence by the immune system. Trace elements such as selenium (Se), zinc (Zn) and copper (Cu) are important for immune competence, particularly in vulnerable population. Poor nutrition status including deficiencies of these vital elements is associated with immune abnormalities and increased susceptibility to infectious diseases. MethodsA comparative study involving a cohort of three hundred and twenty-five (325) participants comprising: 166 persons living with HIV (PLWH) (consisting of 100 on HAART and 66 HAART-treatment naive) and one hundred and fifty-nine (159) non-HIV controls were recruited. Waist to hip ratio and dietary habits were assessed to determine respondents’ nutritional status. Serum Zn, Se and Cu concentrations were estimated by neutron activation method. ResultsMean body mass index (BMI) of respondents was 24.7±4.8 kg/m2. Dietary recommended intakes (DRIs) of macronutrient [energy (69%), carbohydrates (86%) and fats (76%)] and micronutrient [(vitamin B2 (63%), vitamin D (15%), folate (47%) and calcium (63%)] were not adequately met by all groups. PLWH on HAART had a significantly higher total body fat (p=0.004) and visceral fat (p<0.001). Dietary intake of Se, Zn and Cu were highest among the controls (47.0±5.4 µg, 12.4±2.9 mg and 843±15.2 mg respectively) and least, among the HAART treatment naïve group (10.1±5.6 µg, 2.1±0.9mg and 438±16.3 mg respectively), although serum concentrations were significantly lower (0.63±0.21 µmol/L, 1.33±0.92 µmol/L and 1.12±0.14 µmol/L; p<0.001, respectively). Dietary intake of Se and Cu were not associated with their serum concentrations, but treatment status was significantly associated with their serum concentrations (p-value<0.001). Respondents on Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP) had higher serum Se and Cu concentrations but lower Zn concentrations compared to those on other medications. ConclusionMultiple nutrient intakes among PLWH were not adequate; thus, dietary counseling and micronutrient supplementation are strongly recommended, as food security strategies by stakeholders involved in the nutrition management of PLWH in Ghana are also needed. Intake of AZT + 3TC + NVP may improve serum concentrations of Se, and Cu, but could negatively affect serum Zn concentration.

Assessment of Oxidative Stress Level in HIV/AIDS Patients on HAART Treatments

Background: Human Immunodeficiency Virus (HIV) infection is associated with the production of reactive oxygen species (ROS) and secondarily cellular damage of varied severity. Highly active antiretroviral therapy (HAART) are currently the therapy of optimal considerations for HIV-infected patients.&#x0D; Aims: The present study was designed to assess the oxidative stress levels in people living with HIV/AIDS on HAART.&#x0D; Methods: A total of one hundred and twenty (120) patients attending the Jos University Teaching Hospital APIN Centre were recruited for the study following the inclusion criteria. Superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in blood samples of recruited patients.&#x0D; Results: Superoxide dismutase (SOD) activities increased in control patients with no significant difference (p&lt;0.05) compared with HAART. However, significant increases (p&gt;0.05) were observed in reduced glutathione (GSH) concentration of control patients compared with HAART and HAART Naïve patients. More so, significant increase (p&gt;0.05) was observed in malondialdehyde (MDA) of HAART Naïve patients compared with HAART treatment and control. No significant differences (p&gt;0.05) was observed in alanine aminotransferase and creatinine in HAART, HAART Naïve compared with the control patients.&#x0D; Conclusion: The study indicated that HIV/AIDS positive patients express reduced levels of SOD, and GSH with an increase level of MDA. This could further lead to oxidative stress complications and thus HAART-naïve patients are encouraged to used HAART to prevent further complication that could arise from oxidative stress.

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Dyslipidemia and associated risk factors among HIV/AIDS patients on HAART in Asmara, Eritrea.

Though the initiation of Highly Active Antiretroviral Therapy (HAART) has led to decreased HIV/AIDS related mortality, the regimen has been reported to be associated with lipid toxicities. Baseline data on such disturbances are required to induce countrywide interventional HIV/AIDS programs. The aim of this study was to determine the frequency and risks of dyslipidemia in HIV patients on HAART medication in Eritrea. A cross sectional study was conducted on HIV/AIDS patients in two national referral hospitals in Asmara, Eritrea. A structured questionnaire was used to collect demographic data and blood sample was taken for analyses of lipid profile tests. Data was analyzed using chi-square test, Post Hoc and logistic regression in SPSS software. The study included 382 participants of whom 256(67%) were females. Their median age, CD4+ T cell count (cell/microliter) and duration of HAART (years) was 45(IQR: 38-51), 434(IQR: 294-583) & 5(IQR: 3-5) respectively. The prevalence of dyslipidemia was 331(86.6%). Increased Low Density Lipoprotein-C (LDL-C) 213(55.8%) was the predominant abnormality. Abacavir was significantly related with highest means of triglycerides (TG) (228.17 ± 193.81) and lowest means of High Density Lipoprotein (HDL-C) (46.94 ± 12.02). Females had substantially higher proportions of TG (aOR = 2.89, 95% CI: 1.65-5.05) and TC/HDL ratio (aOR = 2.33, 95% CI: 1.40-3.87) and low HDL-C (aOR = 2.16, 95% CI: 1.34-3.48). Increased age was related with increased pro-atherogenic lipid parameters. High LDL-C was more infrequent in non-smokers (aOR = 0.028, 95% CI: 0.12-0.69). The study showed a high prevalence of dyslipidemia in HIV-patients receiving HAART in Eritrea. Sex, age and smoking practice were among key factors associated with dyslipidemia. The necessity to assess lipid profiles and other cardiovascular risk factors before initiation of HAART treatment and continuous monitoring during therapy is mandatory.

Cardiac Abnormalities of People Living with HIV: A Comparative Study Between HAART Experience and Treatment Naïve Groups in Ghana.

PurposeThis study determined electrocardiographic and echocardiographic abnormalities of people living with HIV (PLWHIV); comparing the findings of PLWHIV on HAART versus treatment naïve groups.Patients and MethodsIn a prospective cross-sectional study, we recruited 157 PLWHIV on Highly Active Antiretroviral Therapy (HAART) and 28 HAART naïve PLWHIV. Clinical examination, electrocardiography and echocardiography were performed on study participants at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. Sociodemographic data and information about the use of HAART or otherwise was obtained. The Chi and Fisher Exact tests were used to find the significance of difference in proportions of abnormalities between PLWHIV on HAART and treatment naïve groups. Statistical analyses were performed on SPSS version 25.0 and GraphPad Prism version 8.0. P-values less than 0.05 were considered to be statistically significant.ResultsEchocardiographic abnormalities in the HAART and treatment naïve groups were 54.1% and 60.7%, respectively. Electrographic abnormalities in the HAART and treatment naïve groups were 45.9% and 50%, respectively. Sinus bradycardia was the most prevalent ECG abnormality in the treatment naïve. Nonspecific T-wave changes (36.1%) and sinus tachycardia (30.6%) were the most common ECG abnormalities seen in HAART treated group. The common echocardiographic abnormalities were pulmonary hypertension (22.7%), pericardial effusion (22.2%) and left ventricular systolic dysfunction (17.8%). There was no significant difference in the proportions of echocardiographic abnormalities between PLWHIV on HAART and the treatment naïve groups (p > 0.05).ConclusionCardiac abnormalities are common in PLWHIV regardless of treatment with HAART. Echocardiographic and electrographic assessments are highly recommended for all PLWHIV.

A Pilot Study of the Psychological Impact of the Anti-Same Sex Marriage Campaigns in the Marriage Equality Referendum on Gay People Living with HIV/AIDS in Taiwan

&lt;p&gt;公投期間愛滋一直被反同婚方用來作為反對同性婚姻的理由，本文期待了解愛滋負面文宣對男同志愛滋 感染者產生的心理影響。本文先多方收集反同婚理由述及愛滋的文宣，並透過愛滋民間團體工作人員招 募受訪者，於2019年4月進行一次性焦點訪談團體，團體前先進行所收集的負面文宣簡報，再進行2.5小 時訪談，之後形成逐字稿進行質性分析。8位男受訪者平均年齡38.75歲，平均感染愛滋11年，均服用抗 愛滋病毒藥物中，都接收過愛滋的負面文宣。研究結果如下:第一、受訪者會取笑文宣內容，或是感到 煩悶、生氣，因應方式會避開、客觀冷靜或是主動教育身邊的人。第二、在愛滋負面文宣下，受訪者面 臨三個兩難的三角關係:(1)受訪者不會想和反同婚方對話，轉而期待官方及其他有力人士澄清; (2)受訪者想提出反證會擔心殃及其他無辜族群;(3)受訪者擔心影響社會大眾對男同性戀者社群的 觀感或被社群切割。第三、受訪者建議愛滋反歧視的宣導，應強調愛滋治療效果、修改官方公布的愛滋 統計分類、與其他團體形成友善聯盟等面向。第四、家人開始討論同性戀議題，讓受訪者有被接納的感 覺，但還是不容易現身愛滋感染者身分。綜上，男同志愛滋感染者對於婚姻平權公投時的歧視愛滋文 宣，陷於內化汙名與外在歧視的處境下，帶來兩難的影響。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Context and Objective: On May 24, 2019, Taiwan becomes the first country in Asia to legalize same sex marriage. However, many supporters felt disappointed by the referendum on marriage equality that took place on November 24, 2018. Marriage equality was discussed in Taiwan before the referendum, which entailed many public hearings and debates. There were alliances opposing same sex marriage (referred to as &amp;quot;anti-same sex marriage groups&amp;quot;), as well as alliance that supported same sex marriage. During these debates, anti-same-sex marriage groups highlighted HIV/AIDS issues as justification for opposing same-sex marriage with arguments that included, &amp;quot;most people infected with HIV are gay&amp;quot;, &amp;quot;gay sex among men is the primary factor in HIV transmission&amp;quot;, &amp;quot; legalizing same sex marriage will cause the spread of HIV/AIDS epidemic&amp;quot;, &amp;quot;Taiwan will become an HIV/AIDS island&amp;quot;, &amp;quot;The cost of HIV/AIDS treatment will consume medical resources,&amp;quot; and &amp;quot;Taiwan should not provide health care benefits to those who got HIV/AIDS.&amp;quot; Internet and social media outlets have promoted numerous negative messages about HIV/AIDS, and the anti-same-sex marriage group still uses &amp;quot;HIV/AIDS&amp;quot; as a reason to repeatedly attack the gay community. The present research aims to understand the psychological impact of negative HIV/AIDS propaganda on gay men living with HIV/AIDS in Taiwan and how they coped during the marriage equality referendum. Methods: We first collected articles, pictures, videos, and news about anti-same- sex marriage justification for discrimination against HIV/AIDS from websites, social media, and mobile APP. We then recruited focus group participants through AIDS service for non-governmental organizations. On the day of the focus group in April 2019, we made a brief presentation on relevant negative propaganda before conducting the 2.5 hours focus group. We then conducted a qualitative content analysis after the verbatim transcript was created. The average age of the eight interviewees was 38.75, and the average years of HIV infection was 11 years. All participants were taking HAART (highly active antiretroviral therapy). The interviewees all stated that they had received negative propaganda messages about AIDS on social media during the marriage equality referendum promotion period. Results: (1) Respondents will make fun of the content of the propaganda, or feel bored and angry. In response, they will avoid, be objective and calm, or take the initiative to educate those around them. (2) Ways to respond to negative propaganda messages: somebody would avoid, disregarded, and simply ignore it; somebody would aim and calm, or somebody would actively educate other people around them. (3) There are three dilemmas: (a) They do not want to have conversations with anti-same sex marriage group that distribute the AIDS- stigma messages and instead look forward to clarification by officials (Taiwan Centers for Disease Control) and other powerful non-government organization; (b) Interviewees do not want to hurt other vulnerable groups during the process that messages are clarified; (c) They are worried about affecting the public’s perception of the gay community or being separated from the gay community. (4) For HIV/AIDS anti-discrimination advocacy recommendations, the effectiveness of HAART treatment should be strengthened, the official classification of HIV/AIDS statistics should be revised, and vulnerable groups that are friendly to HIV/AIDS should be invited to form alliances. (5) In particular, some of their family members began to discuss homosexuality issues, making the interviewee feel accepted, but it was still not easy to show up as a PLWHA. Discussion and Conclusion: Based on the research results, this study suggests: (1) Self-stigma is deeply rooted in PLWHA; (2) Public anti- discrimination education for HIV/AIDS needs to be promoted as soon as possible, especially on HAART treatment effects. Gay men with HIV/AIDS are discriminated against HIV/AIDS in the marriage equality referendum, and they are caught in a situation that includes both self-stigma and external discrimination.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

A Real-world Evidence-based Management of HIV by Differential Duration HAART Treatment and its Association with Incidence of Oral Lesions.

BackgroundThe efficacy of highly active antiretroviral therapy (HAART) can be estimated by the immunological response and the incidence of opportunistic infections.ObjectiveThis study aimed at evaluating the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV.MethodsThis single-center, retrospective, and real-world study included patients with HIV, grouped into a treatment group and treatment-naïve group, of which the former was further divided into 6, 12, and 18 months based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination.ResultsIn 246 patients with HIV, CD4 counts increased significantly post-HAART compared to pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated groups. A significant association of HAART with the CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-months and 18-months treatment groups (P<.05). The occurrence of oral lesions reduced significantly in the treatment group.ConclusionWe observed a better response to the HAART regimen with 18-months of duration than 12-months and 6-months therapies and reduction in oral lesions.

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient

BackgroundHIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. MethodsFrom March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/μL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/μL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. ResultsPatients in low-CD4 group have lower proportion of CD3−CD56dimCD16+ NK cell subset, but have higher proportion of CD3−CD56−CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3−CD56−CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3−CD56−CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). ConclusionsThere are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3−CD56−CD16+ NK cell subset before treatment is related with HAART efficacy.

Computerized tomographic brain findings of CNS manifestations in HIV/AIDS patients receiving HAARTS treatment

Background: Despite current availability of highly active antiretroviral therapy (HAART) in our hospital, neurologic complications of HIV are common. Aim: The aim of this study was to document brain computed tomography (CT) findings in HIV patients receiving HAART who developed neurological complications and to examine the relationship of these findings with CD4 cell counts. Materials and Methods: Twenty patients with central nervous system symptoms out of 200 HIV/AIDS patients receiving HAART at the HIV Clinic of Federal Teaching Hospital, Gombe, were retrospectively studied. The findings were reviewed alongside their clinical features, CD4 + count, and HAART history. Results: CT findings were positive in 12 (60%) of the patients, while no abnormality was seen in 8 (40%). The most common brain abnormality was atrophy (35%). Two out of five patients (40%) with CD4 counts &gt;200 had abnormal CT findings compared with 9 out of 14 patients (64%) with CD4 counts &lt;200 cells who had CT abnormalities. This finding was statistically significant (R = 0.864, P = 0.00). Conclusion: There is high incidence of neurological complications and positive brain CT scan among the patients who defaulted from HAART treatment and with CD4 cell counts of &lt;200 cells/microliter.

Rapid, user-friendly, and inexpensive detection of azidothymidine.

Strict adherence to highly active antiretroviral therapy (HAART) is very important to improve the quality of life for HIV-positive patients to reduce new infections and determine treatment success. Azidothymidine (AZT) is an antiretroviral drug commonly used in HAART treatment. In this research, an "add, mix, and measure" assay was developed to detect AZT within minutes. Three different probes designed to release fluorophores when samples containing AZT are added were synthesized and characterized. The limit of detection to AZT in simulated urine samples was determined to be 4μM in 5min for one of the probes. This simple and rapid point-of-care test could potentially be used by clinicians and health care workers to monitor the presence of AZT in low resource settings.

Impact of Insurance Status on Outcomes in Patients with AIDS-Defining Cancers

Background: Mortality among people living with the human immunodeficiency virus (PLWH [HIV]) diagnosed with acquired immunodeficiency syndrome (AIDS)-defining cancers has greatly decreased with the advent of highly active antiretroviral therapy (HAART). Recent investigations exploring the impact of insurance coverage have concluded that PLWH with public insurance have greater mortality than their privately insured counterparts. One avenue to augment medical coverage is the Ryan White HIV/AIDS Program, first authorized by Congress in 1990 to provide primary care and support services to PLWH. This study sets out to elucidate whether insurance coverage and Ryan White assistance affect treatment parameters and survival rates in PLWH diagnosed with Kaposi sarcoma (KS) and non-Hodgkin lymphomas (NHL). Methods: This was a retrospective cohort study of PLWH diagnosed with KS or NHL between 2004 and 2018. Baseline characteristics including demographics, insurance coverage, Ryan White assistance, CD4+ T-cell counts, HIV viral load, HAART treatment, performance status, and disease stage were collected. Participants were classified as having private insurance, Medicare, Medicaid, or no insurance. Treatment regimens were assessed as "optimal" or "suboptimal" using the National Comprehensive Cancer Network guidelines for AIDS-related KS and lymphomas as benchmark. Hazard ratios (HR) for survival were calculated using Cox proportional hazards regression models. Results: Among 191 participants with AIDS-defining cancers, 107 had KS, and 96 had aggressive NHL. 18% had private insurance, 14% had Medicare, 46% had Medicaid, and 23% had no health insurance; 44% received Ryan White assistance. Participants with Medicare and those without Ryan White assistance were older. Those with Ryan White assistance also had better performance status (defined as having an Eastern Cooperative Oncology Group score of 0 to 2). There were no significant differences in CD4+ T-cell counts, HIV viral loads, HAART adherence, treatment delays, regimen selection, and response rates across the insurance and Ryan White groups. The median treatment delay for all participants was 20 days. In general, participants with Medicare had lower overall survival than privately insured participants (HR 2.99, 95% confidence interval [CI] 1.14-7.87, p = 0.027). Participants without Ryan White assistance also had lower overall survival (HR 2.82, 95% CI 1.49-5.35, p = 0.002) and progression-free survival (HR 2.56, 95% CI 1.47-4.44, p &amp;lt; 0.001) than those with assistance. Other factors that influenced overall survival were age (adjusted HR 1.04 per year of age; 95% CI 1.01-1.06; p = 0.007), Hispanic ethnicity (adjusted HR 0.46 compared to Whites; 95% CI 0.24-0.91; p = 0.025), and poor performance status (adjusted HR 6.14; 95% CI 3.39-11.12; p &amp;lt; 0.00001). Conclusions: Our study is among the first to examine the impact of insurance coverage on outcomes in AIDS-defining malignancies. We find that PLWH with Medicare and those not receiving Ryan White assistance have lower survival. These differences may be ascribed in part to discrepancies in age, performance status, and prevalence of AIDS- and non-AIDS-related comorbidities. Reassuringly, our analysis suggests Ryan White assistance, despite its coverage limitations, is not associated with increases in treatment delays or suboptimal regimens. Nevertheless, the importance of dedicated care for this population at a multidisciplinary HIV/AIDS and comprehensive cancer center should not be undervalued. Future research should focus on whether the observed differences can be more broadly replicated in the United States. Figure Disclosures No relevant conflicts of interest to declare.

Diffusion tensor magnetic resonance imaging of white matter integrity in patients with HIV-associated neurocognitive disorders.

BackgroundThis study investigated the efficacy and neurotoxicity of highly active antiretroviral therapy (HAART) by evaluating white matter (WM) injury using diffusion tensor magnetic resonance imaging (DTI) in patients with human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND).MethodsForty-six patients with HAND underwent DTI before and every six months during HAART treatment. DTI data, including fractional anisotropy (FA) and mean diffusivity (MD) values of structural WM before and after HAART, were compared. The relationship between DTI values and plasma viral loads was tested. MD was more sensitive than FA for evaluating WM injury in HAND-positive patients.ResultsFollowing 12 months of HAART, increased MD values (compared to 6 months of HAART) were observed in the right temporal lobe, right parietal lobe, right occipital lobe, right anterior limb of the internal capsule, right lenticular nucleus, the right cerebral peduncle, left caudate nucleus, left dorsal thalamus, and left posterior limb of the internal capsule. MD values in the left genu of the internal capsule (r=0.350, P=0.017) and left corona radiata (r=0.338, P=0.021) were positively correlated with plasma viral loads.ConclusionsDTI may be useful for assessing the efficacy and neurotoxicity of HAART in HAND-positive patients. Starting HAART may halt WM injury; however, prolonged HAART could worsen WM injury, highlighting the importance of optimal HAART duration.

Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium.

Simple SummaryIn 2016, globally, 36.7 million people were living with Human Immunodeficiency Virus (HIV), of which 53% had access to anti-retroviral therapy (ART) (UNAIDS 2017 Global HIV Statistics). The risk of Human Papillomavirus (HPV) associated oropharyngeal, cervical and anal cancers are higher among patients infected with HIV in the era of ART. Generally, HPV infections are self-limiting, however, persistent HPV infection is a major risk to carcinogenic progression. Long intervals between initial infection and cancer development imply cofactors are involved. Co-factors that increase infectivity, viral load, and persistence increase risk of cancer. We propose that the ART Protease Inhibitors (PI) class of drugs are novel co-factors that regulate HPV infection in HIV-infected patients. We developed a model system of organotypic epithelium to study impact of PI treatment on HPV16 infection. Our model could be used to study mechanisms of HPV infection in context of ART, and for developing drugs that minimize HPV infections.Epidemiology studies suggest that Human Immunodeficiency Virus (HIV)-infected patients on highly active anti-retroviral therapy (HAART) may be at increased risk of acquiring opportunistic Human Papillomavirus (HPV) infections and developing oral and cervical cancers. Effective HAART usage has improved survival but increased the risk for HPV-associated cancers. In this manuscript, we report that Protease Inhibitors (PI) treatment of three-dimensional tissues derived from primary human gingiva and cervical epithelial cells compromised cell-cell junctions within stratified epithelium and enhanced paracellular permeability of HPV16 to the basal layer for infection, culminating in de novo biosynthesis of progeny HPV16 as determined using 5-Bromo-2′-deoxyuridine (BrdU) labeling of newly synthesized genomes. We propose that HAART/PI represent a novel class of co-factors that modulate HPV infection of the target epithelium. Our in vitro tissue culture model is an important tool to study the mechanistic role of anti-retroviral drugs in promoting HPV infections in HAART-naïve primary epithelium. Changes in subsequent viral load could promote new infections, create HPV reservoirs that increase virus persistence, and increase the risk of oral and cervical cancer development in HIV-positive patients undergoing long-term HAART treatment.

Computerized tomographic brain findings in HIV/AIDS patients on highly active antiretroviral therapy treatment presenting with central nervous system manifestations in Gombe, North-East, Nigeria

Background: Despite the current availability of highly active antiretroviral therapy (HAART) in our hospital, neurologic complications of HIV still occur. Aim: The aim of this study was to document brain computed tomography (CT) findings in HIV patients receiving HAART who developed neurological complications and to examine the relationship of these findings with CD4 cell counts. Materials and Methods: Twenty patients with central nervous system symptoms out of 200 HIV/AIDS patients receiving HAART at the HIV Clinic of Federal Teaching Hospital, Gombe, were retrospectively studied. The findings were reviewed alongside their clinical features, CD4+ count, and HAART history. Results: CT findings were positive in 12 (60%) of the patients, while no abnormality was seen in 8 (40%) of the patients. The most common brain abnormality was atrophy (35%). Two out of 5 patients (40%) with CD4 counts >200 had abnormal CT findings compared with 9 out of 14 patients (64%) with CD4 counts <200 cells who had CT abnormalities. This finding was statistically significant (R = 0.864, P = 0.00). Conclusion: There is a high incidence of neurological complications and positive brain CT scans among the patients who defaulted from HAART treatment and with CD4 cell counts of <200 cells/μL.