Antiretroviral Therapy In Patients Research Articles

The effectiveness of treatment depending on an adherence to dispensary observation and antiretroviral therapy in patients with HIV infection

Aim. Determination of the causes of deaths and analysis of the survival of people living with HIV, depending on an adherence to dispensary observation and treatment. Materials and methods. The analysis of socio-demographic characteristics and clinical and laboratory data of 284 adult HIV patients observed in 1999–2011 at the Lomonosov Interdistrict Hospital named after I. N. Yudchenko was carried out. Patients who followed the prescribed monitoring regimen (at least 2 times a doctor’s visit during the year) were considered committed to dispensary supervision. Patients who observed the regularity and continuity of monitoring and receiving antiretroviral therapy (ART) were considered committed to treatment. Among the patients included in the study, 115 people were committed to treatment or follow-up and 169 patients were non-committed. Objective (biological) indicators of adherence and effectiveness of treatmentwere the number of CD4 lymphocytes and the level of HIV viral load. Based on the method of comparing survival curves, factors related to the life expectancy of HIV patients were assessed, taking into account the gender of patients, their adherence to monitoring and treatment, indicators of HIV viral load and the number of CD4 lymphocytes and the outcome of the disease from the moment of registration at the dispensary and over the next 120 months (after 3 months, 6 months, 1.5 years, 2 years, 5, 7 and 10 years). Results and discussion. Significant differences were found in the survival curves of patients who received and did not receive ART (117.9 and 91.4 months, p<0.005) and patients who were committed and non-committed to therapy (116.9 and 83.8 months, p<0.005). Regardless of adherence to outpatient follow-up and therapy, the survival time of women compared to men for the entire follow-up period was longer (105.0 and 92.4 months, respectively, p<0.005). Among those committed to treatment, 21% of patients died due to concomitant somatic pathology, 5% from injuries incompatible with life. In the group of those committedto follow–up, the causes of deaths in 12% were various somatic pathology, brain lymphoma — in 1% and injuries incompatible with life — in 3% of cases. The highest mortality rates were recorded among patients who were not exposed to ART (71%) and the routine of follow-up (52%). Almost half of these patients (49%) died from secondary HIV infections, of which 85% of cases were posthumously diagnosed with tuberculosis, mainly the pulmonary form of the disease. The second most common cause of death was violent death, including drug poisoning. Conclusion. Regular dispensary observation, timely initiation of ART and adherence to therapy make it possible to control the disease, prevent the development of opportunistic pathology, and improve the quality and life expectancy of patients with HIV infection. Despite the increased availability of ART and strategies for active involvement and retention of patients in dispensary care, issues of patient adherence to therapy remain key in the management of HIV patients.

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/μCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Factors Associated with Virological Failure in First-Line Antiretroviral Therapy in Patients Diagnosed with HIV-1 between 2010 and 2018 in Israel.

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010-2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010-2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015-2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 <200 cells/mmᶟ with AIDS-defining conditions (HR = 2.75, 95%CI:1.52-4.97, p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01-3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF.

1576. Implementation of a Pharmacist-Driven Initiation of Antiretroviral Therapy in Patients Newly Diagnosed with Human Immunodeficiency Virus

Abstract Background Human Immunodeficiency Virus (HIV) infects over one million people annually. A major barrier to ending this pandemic is access to care. Prompt antiretroviral therapy (ART) initiation after diagnosis reduces time to viral suppression, decreases rates of opportunistic infections, and increases patient retention. At University of Kentucky HealthCare, there was a significant wait time from intake appointment to ART initiation with a provider. Beginning in November 2019, the HIV clinical pharmacist developed a program to initiate ART at intake appointments to curb this delay.This study was conducted to evaluate the impact of this initiative. Methods We conducted a retrospective, quasi-experimental study assessing newly diagnosed HIV ART-naïve adult patients pre- and post-implementation of the pharmacist-driven ART initiation. Exclusion criteria included initial HIV-1 RNA &amp;lt; 40 copies/mL (undetectable) and patients transferring care. Those enrolled between November 2017 to October 2019 were included in the pre-group and those enrolled from November 2019 to November 2021 in the post-group. The primary outcome was time to undetectable from ART prescribing. Secondary outcomes included time to HIV-1 RNA &amp;lt; 200 copies/mL from ART prescribing, and time to undetectable from HIV-1 diagnosis. Results Overall, we included 185 patients (pre-group=104 and post group=81). Undetectable was achieved in 95.5% of patients. Demographics were similar between the groups (Table 1). Median days to undetectable (63.0 vs 56.5; p=0.518) and HIV-1 RNA &amp;lt; 200 copies/mL (49 vs 43; p=0.388) from ART prescribing were similar between the two groups. Median days to undetectable from diagnosis (122 vs 85; p=0.004) and days to ART prescribing from initial visit (31 vs 0; p=0.001) were significantly shorter in the post-group. Median days to initial visit from HIV-1 diagnosis were shorter in the pre-group (13.5 vs 18.0; p=0.015). One-year retention was similar (93.2% vs 90.0%; p=0.433). Conclusion Our study showed a significantly shorter time to undetectable from HIV-1 diagnosis with ART initiation by a clinical pharmacist at intake visits. Additionally, retention of care remained similar despite ART initiation prior to provider visit. This initiative improved timely access to care at our institution. Disclosures All Authors: No reported disclosures

Cost-utility analysis of the fixed-dose combination of dolutegravir/abacavir/lamivudine as initial treatment of HIV+ patients in Spain

ObjectiveFixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients.The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ ABC/3TC) versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and darunavir/r (DRV/r) or raltegravir (RAL) with emtrici- tabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. MethodThe ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/ EFV), and the fixed-dose combinations of emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) with darunavir/r (DRV/r) or ral- tegravir (RAL). The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015). The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. ResultsTreatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY), vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY), and vs. RAL + FTC/TDF or ABC/3TC (-1 005 117.13€/QALY). All the sensitivity analyses performed showed the consistency of these findings. ConclusionsWith the premises considered, treatment initiation with DTG/ABC/3TC STR appears to be the most cost-effective option in ARTnaive HIV infected patients from the Spanish Health System perspective

Factors related to delayed initiation of antiretroviral therapy among patients with clinically eligible HIV-infected

Background: Human Immunodeficiency Virus (HIV), namely a virus that reduces the ability of the human immune system, so that sufferers are susceptible to various diseases, the wider scope of ARV administration certainly has a positive impact in reducing mortality and morbidity, improving the quality of life of patients with HIV and AIDS.Purpose: To determine the factors associated with delayed initiation of antiretroviral therapy in Human Immunodeficiency Virus patients at the VCT (Voluntary Counseling and Testing) Clinic of Pringsewu Hospital in 2022.Method: This type of quantitative research, using a cross sectional design. The population of this study were HIV positive patients at the Pringsewu Regional General Hospital Clinic, Lampung for the year 2022, namely 174 patients, using the side total technique. Univariate data analysis, bivariate with chi square and multivariate with multiple logistic regression tests.Results: The result showed that the factors associated with delayed initiation of antiretroviral therapy in Human Immunodeficiency Virus patients at the VCT Clinic at Pringsewu General Hospital in 2022 were Socioeconomic Status (p value=0.009), education level (p value=0.001, opportunistic infections (p value= 0.001), HIV/AIDS Stigma (p value=0.003), and Access (p value=0.018). The most dominant factor associated with delayed initiation of antiretroviral therapy in patients with Human Immunodeficiency Virus infection was access (95% CI, p=0.027 and OR; 3.738).Conclusion: Antiretroviral therapy (ARV) delays in PLWHA are strongly influenced by low socioeconomic status, low education level, presence of opportunistic infections, positive stigma and remote access to healthcare services.Suggestion: Management at the hospital's VCT clinic is suggested to make guidelines or standardized services, educate about the importance of ARVs, provide motivation, and carry out consistent control of ARV therapy. The management always promotes the importance of awareness and adherence in carrying out ARV therapy which will have many benefits in improving quality of life, healthy behavior, and extending life span.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

The Imbalance Between Intestinal Th17 and Treg Cells Is Associated with an Incomplete Immune Reconstitution During Long-Term Antiretroviral Therapy in Patients with HIV.

Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4+ T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4+ T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage.

HIV-1 DNA Testing in Viremic Patients Identifies More Drug Resistance Than HIV-1 RNA Testing.

The Department of Health and Human Services HIV-1 Treatment Guidelines recommend drug resistance testing in HIV-1 RNA to guide the selection of antiretroviral therapy in patients with viremia. However, resistance-associated mutations (RAMs) in HIV-1 RNA may reflect only the patient's current regimen and can be lost during prolonged absence of therapy. We determined if HIV-1 DNA testing can provide drug resistance information beyond that identified in contemporaneous plasma virus. This was a retrospective database review of results obtained for patients with viremia for whom commercial HIV-1 RNA and HIV-1 DNA drug resistance testing was ordered on the same day. Resistance-associated mutations and drug susceptibility calls were compared between paired tests, and the effect of HIV-1 viral load (VL) on test concordance was assessed using Spearmen's rho correlation. Among 124 paired tests, more RAMs were identified in HIV-1 DNA in 63 (50.8%) cases, and in HIV-1 RNA in 11 (8.87%) cases. HIV-1 DNA testing captured all contemporaneous plasma virus RAMs in 101/117 (86.3%) cases and identified additional RAMs in 63/117 (53.8%) cases. There was a significant positive correlation between the viral load at the time of resistance testing and the percentage of plasma virus RAMs detected in HIV-1 DNA (rs = 0.317; P < .001). In 67 test pairs demonstrating pan-sensitive plasma virus, resistance in HIV-1 DNA was seen in 13 (19.4%) cases. HIV-1 DNA testing identified more resistance than HIV-1 RNA testing in most patients with viremia and may be informative in patients whose plasma virus reverts to wild-type following therapy discontinuation.

Effectiveness of mHealth on Adherence to Antiretroviral Therapy in Patients Living With HIV: Meta-analysis of Randomized Controlled Trials.

The World Health Organization recommends that all adults with HIV adhere to antiretroviral therapy (ART). Good adherence to ART is beneficial to patients and the public. Furthermore, mHealth has shown promise in improving HIV medication adherence globally. The aim of this meta-analysis is to analyze the effectiveness of mHealth on adherence to antiretroviral therapy in patients living with HIV. Randomized controlled trials (RCTs) of the association between mHealth and adherence to ART published until December 2021 were searched in electronic databases. Odds ratios (ORs), weighted mean differences, and 95% CIs were calculated. This meta-analysis was performed using the Mantel-Haenszel method or the inverse variance test. We evaluated heterogeneity with the I2 statistic. If I2 was ≤50%, heterogeneity was absent, and a fixed effect model was used. If I2 was >50%, heterogeneity was present, and a random effects model was used. A total of 2163 participants in 8 studies were included in this meta-analysis. All included studies were RCTs. The random effects model was used for a meta-analysis of the effects of various intervention measures compared to routine nursing; the outcome was not statistically significant (OR 1.54, 95% CI 0.99-2.38; P=.05). In the subgroups, only short messaging service (SMS)-based interventions significantly increased adherence to ART (OR 1.76, 95% CI 1.07-2.89; P=.03). Further analysis showed that only interactive or bidirectional SMS could significantly increase ART adherence (OR 1.69, 95% CI 1.22-2.34; P=.001). After combining the difference in CD4 cell count before and after the interventions, we concluded that there was no statistical heterogeneity among the studies (I2=0%; tau2=0.37; P=.95). Interactive or bidirectional SMS can enhance intervention effects. However, whether mHealth can improve adherence to ART in patients with HIV needs further study. Owing to a lack of the required significant staff time, training, and ongoing supervision, there is still much more to do to apply mHealth to the clinical use of ART for patients living with HIV. PROSPERO CRD42022358774; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=358774.

Associated oral manifestations with HIV southeastern Brazilian patients on antiretroviral therapy

ObjectivesThis study aimed to assess the prevalence of oral lesions in patients living with HIV infection and their association with CD4 count, viral load, and antiretroviral therapy in patients with HIV. MethodsA cross-sectional study was conducted on a sample of 161 patients attending the… All the patients were examined for their oral lesions, current CD4 counts, type, and duration of the therapy. Data analyses were carried out using Chi-Square, Student T/Mann-Whitney, and logistic regression tests. ResultsOral lesions were observed in 58.39% of patients with HIV. Periodontal disease with 78 (48.45%) or without mobility 79 (49.07%) was observed more frequently, followed by hyperpigmentation of oral mucosa 23 (14.29%), Linear Gingival Erythema (LGE) 15 (9.32%), candidiasis pseudomembranous 14 (8.70%). Oral Hairy Leukoplakia (OHL) was observed only in 3 (1.86%). A relationship between periodontal disease with dental mobility and smoking was found (p=0.04), as well duration of treatment (p=1.53e-3) and age (p=0.02). Hyperpigmentation was related to race (p=0.01) and smoking (p=1.30e-6). CD4 count, CD4:CD8 ratio, viral load, or type of treatment were not associated with oral lesions. Logistic regression showed that the duration of treatment has a protective effect on the periodontal disease with dental mobility (OR = 0.28 [−2.27 to −0.25]; p-value=0.03), independent of age or smoking. To hyperpigmentation, the best model included smoking (OR=8.47 [1.18–3.10], p= 1.31e-5), without race or type and duration of treatment. ConclusionAmong HIV patients undergoing antiretroviral treatment, oral lesions can be observed, predominantly periodontal disease. Pseudomembranous candidiasis and oral hairy leukoplakia were also observed. No relationship was found between associated oral manifestations in HIV patients and the start of the treatment, TCD4+ and TCD8+ cell count, TCD4:TCD8 ratio, or viral load. The data indicate that there is a protective effect of duration of treatment with relation to periodontal disease with mobility and that hyperpigmentation seems to be more related to smoking than type and duration of treatment. Level of evidenceLevel 3 (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence").

In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs

It has been considered that reduced susceptibility to antiretroviral drugs is influenced by drug adherence, drug tolerance and drug-resistance-related mutations in the HIV genome. In the present study, we assessed the intrinsic high viral growth capability as a potential viral factor that may influence their susceptibility to antiretroviral drugs using an in vitro model. Phytohemagglutinin-activated peripheral blood mononuclear cells (1.5 × 106 cells) were infected with HIV isolates (106 copies/mL). The culture was carried out at different concentrations (0.001-20 μM) of 13 synthetic antiretroviral compounds (six nucleoside/nucleotide reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase inhibitor, four integrase inhibitors, and two protease inhibitors), and HIV production was assessed using HIV-RNA copies in culture. The 90% inhibitory concentration (IC90) and pharmacokinetics of an antiretroviral agent were used as parameters to determine the reduced antiretroviral drug susceptibility of HIV isolates with high growth capability to synthetic antiretroviral compounds. The high growth capability of HIV isolates without any known drug resistance-related mutation affected their susceptibility to tenofovir (IC90 = 2.05 ± 0.40 μM), lamivudine (IC90 = 6.83 ± 3.96 μM), emtricitabine (IC90 = 0.68 ± 0.37 μM), and efavirenz (IC90 = 3.65 ± 0.77 μM). These antiretroviral drugs showed IC90 values close to or above the maximum plasma concentration against HIV isolates with high growth capability without any known drug resistance-related mutation. Our results may contribute to the development of effective strategies to tailor and individualize antiretroviral therapy in patients harboring HIV isolates with high growth capability.

Impact of delayed initiation of antiretroviral therapy in patients with HIV infection

Objective — to analyze the effect of the duration of the period from the moment of infection to the appointment of antiretroviral treatment in patients with HIV infection as a predictor of an unfavorable course of the disease. &#x0D; Materials and methods. A retrospective and prospective study was conducted among a cohort of people living with HIV (PLHIV), which included 450 patients. The observation lasted 60 months. 63 patients died from HIV-related causes, 14 from non-HIV and immune reconstitution inflammatory syndrome (IRIS) causes, 69 patients interrupted antiretroviral therapy (ART) for various reasons during the follow-up period. By the end of the follow-up period, 304 patients remained on ART. Statistical processing of the results was carried out using the STATISTICA v. 6.1 application package. &#x0D; Results and discussion. Based on the results of a correlation analysis of clinical and laboratory parameters of a cohort of HIV-infected patients, 10 main risk factors were selected, including the delayed initiation of antiretroviral treatment. After 5 years of follow-up, the main reason for the loss of patients from the cohort was interruption of therapy — 69 (15.3 %) people, 63 (14.0 %) died from HIV-related causes, and 14 (3.1 %) died from causes unrelated to HIV and IRIS. Causes associated with the undesirable clinical outcomes of ART were noted in 30.4 % of people — allergic reactions, taking therapy together with anti-TB therapy, in turn, led to the development of IRIS and an increase in adverse events. &#x0D; Conclusions. The analysis shows that despite the high intensity of the prescribed primary treatment regimens for patients with HIV infection, such a factor as the delayed initiation of ART has a significant negative impact on the further course of HIV infection and the development of adverse events, worsening the prognosis of the disease.

A model for explaining adherence to antiretroviral therapy in patients with HIV/AIDS: A grounded theory study.

Maintaining a high level of adherence to antiretroviral therapy is a challenge among HIV/AIDS patients. The study aimed to explore the process of adherence to treatment with a grounded theory approach to help physicians and planners develop strategies to increase adherence to treatment. We conducted in-depth interviews and a focus-group discussion. The data were collected from 2016 to 2018. The participants were 39 HIV/AIDS patients treated with antiretroviral, their relatives (three people) and two treatment staff. The study was conducted at the Behavioural Counselling Center of Imam Khomeini Hospital, located in Tehran, the capital of Iran. The data were analysed at the stages of "analysis for concepts," "analysis for context," "bringing process into the analysis" and "integrating." We obtained a conceptual model to explain the relationship between the categories. "Motivation" was identified as the core variable and the "Becoming resilient" explained the adherence process. Several factors including the interfering factors, contextual factors and resilience factors were identified. The interfering and contextual factors, in the absence of the resilience factors, lead to decreased motivation and increased poor adherence to treatment. The role of motivation in long-term adherence should be emphasised. We think strategies such as helping individuals with HIV/AIDS to form support networks, empowering and encouraging them to seek spiritual help will motivate them to maintain a long-term use of antiretroviral medications and, hence, become more resilient.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study

BackgroundThe mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients.MethodsThis was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks.ResultsThe present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started.ConclusionsEarly ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP.Clinical trial registrationThe present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

Directing HIV-1 for degradation by non-target cells, using bi-specific single-chain llama antibodies

While vaccination against HIV-1 has been so far unsuccessful, recently broadly neutralizing antibodies (bNAbs) against HIV-1 envelope glycoprotein were shown to induce long-term suppression in the absence of antiretroviral therapy in patients with antibody-sensitive viral reservoirs. The requirement of neutralizing antibodies indicates that the antibody mediated removal (clearance) of HIV-1 in itself is not efficient enough in these immune compromised patients. Here we present a novel, alternative approach that is independent of a functional immune system to clear HIV-1, by capturing the virus and redirecting it to non-target cells where it is internalized and degraded. We use bispecific antibodies with domains derived from small single chain Llama antibodies (VHHs). These bind with one domain to HIV-1 envelope proteins and with the other domain direct the virus to cells expressing epidermal growth factor receptor (EGFR), a receptor that is ubiquitously expressed in the body. We show that HIV envelope proteins, virus-like particles and HIV-1 viruses (representing HIV-1 subtypes A, B and C) are efficiently recruited to EGFR, internalized and degraded in the lysosomal pathway at low nM concentrations of bispecific VHHs. This directed degradation in non-target cells may provide a clearance platform for the removal of viruses and other unwanted agents from the circulation, including toxins, and may thus provide a novel method for curing.

Оценка эффективности антиретровирусной терапии у больных ВИЧ / туберкулез на основании показателей общих липидов сыворотки крови

Under the ongoing epidemic of HIV-infection, the incidence of tuberculosis continues to grow without a visible tendency to decrease. It is necessary to improve treatment approaches that allow more flexibility in determining the effectiveness of antiretroviral therapy (ART) at the very beginning of treatment for HIV / tuberculosis coinfection. Lipids play an important role in the formation of a tuberculous lesion. The study of the total lipids dynamics in HIV/tuberculosis coinfection has the potential for an early assessment of the ART effectiveness. The purpose is to evaluate the effectiveness of the course of antiretroviral therapy in patients with HIV / tuberculosis at 4B stage based on the values of total serum lipids. Material and methods. The study included 300 patients with HIV / tuberculosis, of which 100 patients received only tuberculosis chemotherapy, 100 patients received ART and 1 TB therapy regimen (TBT), 100 patients received ART and 4 TBT regimen. Clinical and laboratory parameters were studied in all patients, the blood serum lipid spectrum was analyzed (total lipids (OL), total phospholipids (OFL), free cholesterol (CX), cholesterol esters (EH), triglycerides (TG), free fatty acids (FFA)) and the effectiveness of the ART was evaluated. To detect early changes in total lipids, the results were analyzed after 1 month. Results. It was found that ART in HIV/tuberculosis patients causes significant positive changes in the metabolism of total lipids (OL, OFL, CX, EH, TG, FFA), largely bringing their values closer to the level of healthy individuals, which is accompanied by a pronounced clinical and radiological effect in the form of more frequent abacylation. Against the background of ART, an inflammatory immunity restoration syndrome (IIRS) developed, which was stopped by pathogenetic therapy.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME AFTER USE OF ANTI-RETROVIRAL THERAPY IN COVID-19

TOPIC: Chest Infections TYPE: Global Case Reports INTRODUCTION: COVID-19 is still an emerging topic and co-existence in HIV patients presents its unique challenge. These patients can range from elite controllers to Acquired immunodeficiency syndrome (T cell CD4 < 200). Throughout our management, we noticed certain trends in our population. Those patients with CD4 T cell < 200 were rarely admitted to hospital with severe cases of COVID-19, requiring if anything minimal oxygen requirements. However, HIV patients who were admitted did not fare well after initiating their anti-retroviral therapy (ART) therapy during index hospitalization. We describe two such cases one in which ART was maintained and one in which ART was help with different outcomes. CASE PRESENTATION: Both patients on admission were admitted for progressive dyspnea with COVID PCR positive, started on ART therapy, given a 10-day course of Dexamethasone 6mg and 5 doses of Remdisivir.Case 1 - 55year old Hispanic male with a history of non-compliance on Triumeq (CD4 count of 34), lymphoma in remission after chemotherapy, and sulfa allergy. On admission he was started on Triumeq, Azithromycin, Clindamycin, Primaquine. Over next 3 days he experienced progressive hypoxia and worsening chest imaging eventually requiring mechanical ventilation.Case 2 - 66year old female non-compliant on ART, and polysubstance abuse. She was also noted to have MSSA pneumonia. She was started on Emricitabine, Tenofovir, Ritonavir, and Atazanorvir. Within 48 hours of ART initiation her oxygen requirement increased. At this time, her antiretrovirals were stopped and started on Solumedrol 40mg twice daily for suspected IRIS. Her respiratory status improved and her oxygen requirements were back to baseline. Upon restarting ART 2 weeks post treatment for IRIS, patient again required an increase in oxygen supplementation. ART was held for an extended period while maintaining opportunistic infection prophylaxis. DISCUSSION: We pose this discussion for the community, as COVID-19 pathophysiology has been hypothesized to be an inflammatory response mitigated by Interleukins and Interferon-gamma, released by CD4 and CD8 T cells {3} Theoretically those with lower CD4 T cells, such as those with AIDs, should produce a lesser inflammatory response;and therefore, be less symptomatic. IRIS is typically determined from clinical context and is seen more frequently in those with CD4 < 100. {1} Treatment is typically steroids with a prolonged taper, with an ongoing discussion on whether ART should be held. {4} CONCLUSIONS: Currently there are no guidelines regarding utilization of ART in HIV patients infected with COVID;which leads to following questions of whether ART be held transiently until the COVID-19 pneumonia has been sufficiently treated? When should ART be restarted in these patients? If a patient's condition is deteriorating, should the patient's ART be held and started on opportunistic infection prophylaxis? REFERENCE #1: Bosamiya, S.S. The immune reconstitution inflammatory syndrome (2011) 56(5) 476-9, Indian J Dermatology. doi : 10.4103/0019-5154.87114 REFERENCE #2: Brown, L.B, Spinelli, M.A., and Gandhi, M. The interplay between HIV and COVID-19: summary of the data and responses to date. (2021) 16(1) 63-73, Current opinion of HIV and AIDs. REFERENCE #3: Kalfaoglu, B., Almeida-Santos, J., Tye, C.A., Satou, Y., and Ono, M. T cell dysregulation in COVID-19 (2020) 29(530) 204-210, Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2020.10.079 DISCLOSURES: No relevant relationships by Obed Adarkwah, source=Web Response no disclosure on file for Anjali Bakshi;No relevant relationships by Louis Gerolemou, source=Web Response No relevant relationships by Aneeta Kumari, source=Web Response No relevant relationships by Nabil Mesiha, source=Web Response No relevant relationships by Steven Miller, source=Web Response No relevant relationships by Kunal Nangrani, source=Web Response No relevant relationships by Jose Orsini, source=Web Response No relevant relationships by Gaurav Parhar, source=We Response no disclosure on file for Dhruv Patel;No relevant relationships by Jason Ravidas, source=Web Response No relevant relationships by jad sargi, source=Web Response No relevant relationships by Viswanath Vasudevan, source=Web Response No relevant relationships by Kiran Zaman, source=Web Response No relevant relationships by John Zeibeq, source=Web Response

PREVALENCE AND CHARACTERISTICS OF TUBERCULOSIS IN HIV-INFECTED PATIENTS CONSIDERING THE 299GLY ALLELE TLR4 GENE CARRIAGE

Human immunodeficiency virus (HIV) infection remains one of the most acute problems of modern medicine. Tuberculosis is known as the leading cause of death among the opportunistic infections in HIV-positive people; moreover, TB is also known as resulting in one of three deaths associated with acquired immunodeficiency syndrome. It should be stressed the TB course against the background of HIV infection demonstrates the atypical characteristics, nonspecific clinical symptoms with increasing frequency of extrapulmonary lesions, minimal radiological manifestations, low frequency of the pathogen excretion, and rapid course of the disease. In recent years, researchers around the world have paid considerable attention to studying the effects of genetic variation of genes on the course of infectious diseases in humans, including HIV and tuberculosis, and in particular, to investigating Tool-receptors, innate immune system receptors, which interact with pathogens and stimulate effector mechanisms of innate immunity. The objective of this study is to determine the prevalence and evaluate the features of the TB course before and during the antiretroviral therapy, considering the carriage of the 299Gly allele of the TLR4 gene. To assess the manifestations, clarify the clinical characteristics of the disease in the dynamics before and during the antiretroviral therapy, a retrospective cohort examination of 181 HIV-positive patients before and after the therapy was carried out. The study has demonstrated that, despite the virological and immunological effectiveness of the treatment, the TB detection in HIV-infected patients taking antiretroviral therapy remained almost constant compared to the period before antiretroviral therapy (17.0% vs. 14.9%, &gt; 0.05). Analysis of genotypes of the TLR4 gene showed that during the observation period before antiretroviral therapy in patients with the 299Gly allele there was a 6.3-fold higher risk of developing of disseminated TB forms (OR = 6.29 [95% 1.20-32.99], p = 0.044), compared with carriers of Asp299Asp genotype. In HIV-infected patients with the 299Gly allele of the TLR4 gene on the background of antiretroviral therapy, the risk of TB development is 3.4 times higher (p = 0.008) than in carriers of its homozygous genotype.