Antiretroviral-treated Patients Research Articles

Prevalence of major INSTI and HIV-1 drug resistance mutations in pre- and antiretroviral-treated patients in Indonesia

Indonesia has one of the highest HIV infection rates in Southeast Asia. The use of dolutegravir, an integrase strand transfer inhibitor (INSTI), as a first-line treatment underscores the need for detailed data on INSTI drug resistance mutations (DRMs). Currently, there is a lack of comprehensive data on DRMs INSTI and other HIV drug resistance in Indonesian patients, both pre- and post-treatment. The aim of this study was to identify the subtypes and drug resistance mutations of the protease, reverse transcriptase, and integrase genes in both treatment-naive and ARV-treated patients in Bandung, West Java, Indonesia. A cross-sectional study was conducted involving HIV-positive patients at Hasan Sadikin Hospital, Bandung, Indonesia, from September 2022 to January 2023. The patients were categorized into two groups: ARV-treated and pre-treatment patients. Peripheral blood mononuclear cells (PBMCs) were processed for DNA extraction, followed by amplification and sequencing of the pol gene to detect mutations and subtypes. The study found that the predominant subtype was CRF01_AE, accounting for 85.4% and 69% of pre-treatment and treated patients, respectively, followed by recombinant forms such as A1/CRF01_AE, CRF01_AE/CRF02_AG, subtype B, and other subtypes. Among ARV-treated/INSTI-naive patients, major INSTI DRMs R263K and Y143H were identified, while pre-treatment patients exhibited accessory integrase DRMs. The most common DRMs detected were non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs, with prevalences of 14.6% and 7% in pre-treatment and ARV-treated patients, respectively. In conclusion, CRF01_AE emerged as the predominant subtype in both pre-treatment and ARV-treated patients in Bandung, underscoring the necessity for ongoing surveillance of integrase DRMs, particularly given the presence of major INSTI DRMs in patients undergoing INSTI treatment.

Related factors to non-adherence to antiretroviral therapy in HIV/AIDS patients

ObjectiveTo identify sociodemographic, clinical, and pharmacological factors associated with nonadherence to antiretroviral treatment in patients with human immunodeficiency virus/acquired immunodeficiency syndrome treated between 2017 and 2020 in four cities in Colombia. MethodAn observational, cross-sectional, retrospective study was conducted of a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome treated between 2017 and 2020. The Morisky-Green scale, the simplified medication adherence questionnaire, and the simplified scale to detect adherence problems to antiretroviral treatment were applied to determine patient adherence. A binomial multiple logistic regression was performed to evaluate the factors that best explain nonadherence. ResultsA total of 9,835 patients were evaluated, of whom 74.4% were men, 71.1% were aged between 18 and 44 years, 76.0% had attended at most secondary school, 78.1% were single, and 97.6% resided in an urban area. After applying three different scales to each patient, 10% of the study population were identified as nonadherent to treatment. The risk of nonadherence was significantly higher in patients who presented any drug-related problem or had an adverse reaction to antiretroviral drugs. ConclusionsThe variables most strongly associated with nonadherence to antiretroviral treatment were drug-related problems, adverse drug reactions, a history of nonadherence to treatment, and psychoactive substance use.

Impact of COVID-19 on Adherence to Treatment in Patients with HIV.

In patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student's t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

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.

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4+ T Cells From HIV-1 Patients.

We described a novel HIV autologous isolation method based in coculturing macrophages and CD4+T-cell-enriched fractions from peripheral blood collected from antiretroviral-treated (ART) HIV patients. This method allows the isolation of high viral titers of autologous viruses, over 1010HIV RNA copies/ml, and reduces the time required to produce necessary amounts for virus for use as antigens presented by monocyte-derived myeloid cells in HIV therapeutic vaccine approaches. By applying these high titer and autologous virus produced in the patient-derived cells, we intended to elicit a boost of the immunological system response in HIV therapeutic vaccines in clinical trials.

Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth

Among CD4+ T cells, T helper 17 (Th17) cells are particularly susceptible to HIV-1 infection and are depleted from mucosal sites, which causes damage to the gut barrier, resulting in a microbial translocation-induced systemic inflammation, a hallmark of disease progression. Furthermore, a proportion of latently infected Th17 cells persist long term in the gastrointestinal lymphatic tract where a low-level HIV-1 transcription is observed. This residual viremia contributes to chronic immune activation. Thus, Th17 cells are key players in HIV pathogenesis and viral persistence. It is, however, unclear why these cells are highly susceptible to HIV-1 infection. Th17 cell differentiation depends on the expression of the master transcriptional regulator RORC2, a retinoic acid-related nuclear hormone receptor that regulates specific transcriptional programs by binding to promoter/enhancer DNA. Here, we report that RORC2 is a key host cofactor for HIV replication in Th17 cells. We found that specific inhibitors that bind to the RORC2 ligand-binding domain reduced HIV replication in CD4+ T cells. The depletion of RORC2 inhibited HIV-1 infection, whereas its overexpression enhanced it. RORC2 was also found to promote HIV-1 gene expression by binding to the nuclear receptor responsive element in the HIV-1 long terminal repeats (LTR). In treated HIV-1 patients, RORC2+ CD4 T cells contained more proviral DNA than RORC2- cells. Pharmacological inhibition of RORC2 potently reduced HIV-1 outgrowth in CD4+ T cells from antiretroviral-treated patients. Altogether, these results provide an explanation as to why Th17 cells are highly susceptible to HIV-1 infection and suggest that RORC2 may be a cell-specific target for HIV-1 therapy.

Progressive multifocal leukoencephalopathy: Insights on pathogenesis and potential treatments

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by the polyomavirus JC (JCV), which affects persons with an impaired immune system, such as in HIV infection, congenital immunodeficiencies or during immunosuppressive or immunomodulant therapies. Currently, there is no effective antiviral treatment for PML and its remission can only be achieved by reversing immune suppression, e.g., by starting antiretroviral treatment in patients with HIV-associated PML or by withdrawing immunosuppressive drugs in other conditions.

Hematological Abnormalities of Adult HIV-Infected Patients Before and After Initiation of Highly Active Antiretroviral Treatment at Debre Tabor Comprehensive Specialized Hospital, Northcentral Ethiopia: A Cross-Sectional Study.

BackgroundHematological abnormalities have been associated with an increased risk of disease progression and death in people living with human immunodeficiency virus (HIV). The use of antiretroviral medications can have a positive or negative effect on the hematological disorder. However, little is known about its impact on hematological parameters in antiretroviral-treated patients in Ethiopia, especially in the study area.MethodsA cross-sectional study was conducted at Debre Tabor Comprehensive Specialized Hospital from September to November 2020. A total of 334 HIV-infected patients taking highly active antiretroviral treatment (HAART) at least for 6 months were selected using a simple random sampling technique. Socio-demographic and clinical characteristics of the study subjects were collected using a semi-structured questionnaire. Hematological and immunological parameters were determined using Sysmex kx-21 hematology analyzer and BD FACS count CD4 analyzer, respectively. Statistical analysis was done using SPSS version 20 statistical software. A P-value <0.05 was considered statistically significant.ResultsA total of 334 HIV patients were included in this study. The prevalence of anemia, leucopenia, neutropenia, lymphopenia and thrombocytopenia were 37.1%, 22.8%, 8.4%, 10.5% and 17.1% before initiation of HAART and 17.4%, 34.2%, 18.8%, 13.1% and 8.3% after initiation of HAART, respectively. There was a significant difference in total white blood cell (WBC) count, absolute neutrophil count (ANC), red blood cell (RBC) count, hemoglobin value, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet and CD4+ T cell counts in HIV patients before and after initiation of HAART (P<0.05).ConclusionThe most common hematological abnormalities observed in this study before and after HAART initiation were anemia, leucopenia, neutropenia, lymphopenia, and thrombocytopenia. However, after beginning HAART, the prevalence of anemia and thrombocytopenia decreased dramatically.

Inconsistent reversal of HIV-1 latency ex vivo by antigens of HIV-1, CMV, and other infectious agents

BackgroundA reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-1 infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV-1 and other common pathogens to reverse latency.ResultsWe obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV-1 and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-1 expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-1 expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation.ConclusionsIn this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-1 latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.

4306 Periodontal disease and the oral microbiome in antiretroviral-treated patients with HIV

OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs healthy controls. METHODS/STUDY POPULATION: In an ongoing cohort study we have been recruiting pre- and post-menopausal women with HIV+ on ART for ≥6 months and HIV- controls matched by menopausal status (target n = 30 per arm; currently HIV+: n = 30 post- and 9 pre-M; HIV-: n = 15 post- and 6 pre-M). Patients age &lt;18 or on antibiotics within 3 mos., except prophylaxis, are excluded. Patients provide saliva, then subgingival plaque collection during a dental examination through scaling from six index teeth. Standard CDC/AAP classifications of periodontitis are used. We will perform 16S rRNA and ITS sequencing to profile bacterial and fungal communities in saliva and plaque. Linear mixed effect regression and differential abundance analyses will be used to identify microbial and mycobial oral signatures of periodontal disease severity in HIV+ and HIV- populations. RESULTS/ANTICIPATED RESULTS: We found a markedly high prevalence of severe periodontal disease in HIV+ women despite ART (59%, compared to 11% in HIV- controls). In post-menopausal women with HIV, saliva bacterial α- and β-diversity in the saliva differed significantly with periodontal disease severity. Fungal α-diversity was also significantly lower in plaque from teeth with severe loss of tissue attachment (CAL ≥4 mm). We identified bacterial and fungal taxa significantly enriched in post-menopausal HIV+ women with severe compared to no or mild periodontitis. We hypothesize, similarly, associations between the oral microbiome and periodontitis in HIV- controls. However, we expect overall diversity metrics to be significantly altered in HIV+ compared to HIV- patients, indicating long-term dysbiosis despite treatment with ART. DISCUSSION/SIGNIFICANCE OF IMPACT: Contrasting associations between the oral microbiome and periodontal disease with respect to HIV will provide evidence for the role of microbiota in accelerated aging phenotype caused by HIV. Our results would also provide rationale for interventions targeting co-morbidities in people living with HIV to account for both inflammation and dysbiosis.

Calcaneal Quantitative Ultrasonography and Urinary Retinol-Binding Protein in Antiretroviral-Treated Patients With Human Immunodeficiency Virus in Uganda: A Pilot Study.

Data on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infected individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein-urinary creatinine ratio (uRBP/uCr) and reduced BMD. We conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infected adults who had been receiving continuous antiretroviral therapy for ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection. DXA BMD measurements were significantly associated (P < .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [P = .03], femoral neck [P < .001], and total hip [P = .002]). Calcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate-sparing regimens in resource-limited settings.

Characteristics and outcomes of antiretroviral-treated HIV-HBV co-infected patients in Canada

BackgroundHepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients.MethodsA retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon’s Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI).ResultsHBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120–360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85–294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02).ConclusionThe prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.

Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.

Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations.

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.

Cerebrospinal fluid HIV-1 escape according to different thresholds and underlying comorbidities: is it time to assess the definitions?

: No consensus has been reached on how to define cerebrospinal fluid HIV-1 escape (CSF-E). We describe its prevalence in 1095 paired CSF-plasma HIV-RNA measurements from antiretroviral-treated patients according to several definitions and neurological affections. CSF-E prevalence varied substantially (9.0-38.9%) and was higher in patients with cerebrovascular disorders, HIV-associated dementia and white matter abnormalities. Considering the variability in HIV-RNA quantification assays, the biological relevance of viral escape at different thresholds needs to be accurately assessed.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients

AimAgeing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. MethodsIncluded were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997–1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, β2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. ResultsAt the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45–56); BMI was 23.0 kg/m2 (21.1–25.4), CD4+ lymphocytes were 620 cells/mm3 (453–790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. ConclusionIn long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

Factores de riesgo y adherencia terapéutica en pacientes infectados por el Virus de la Inmunodeficiencia Humana en Cotopaxi, Ecuador.

Introducción: Ecuador se ubica entre los cinco países de América Latina con mayor transmisión de VIH. Las estadísticas de ONUSIDA en el 2017, demostraron un incremento, 33.000 PVVS en Ecuador, de ellos 32.000 son adultos con edades comprendidas entre 15 y 49 años: 9.900 mujeres y 22.000 hombres. La novedad de esta investigación viene dada por la identificación de los factores de riesgo para la infección por VIH y estimación de la adherencia terapéutica de los pacientes infectados, en una de las provincias más pobladas.&#x0D; Objetivo: Evaluar los factores predisponentes a la infección por el Virus de la Inmunodeficiencia Humana y la adherencia al tratamiento antirretroviral en los pacientes de la Provincia Cotopaxi en Ecuador.&#x0D; Material y métodos: Estudio explicativo observacional de cohorte prospectivo. La población estuvo constituida por todos los pacientes con diagnóstico de VIH atendidos en la Clínica de VIH del Hospital Provincial General de Latacunga durante el periodo 18 de septiembre del 2018 al 18 de septiembre del 2020. La muestra estuvo compuesta por 80 casos nuevos de infección por VIH que se diagnosticaron a partir del 18 de septiembre del 2018 al 31 de diciembre del 2019, acepten ser incluidos en la investigación.&#x0D; Resultados: Predominó el sexo masculino en 97,1 %, la raza mestiza en el 100 %, el grupo de edad de 35-45 años en el 52,8 %, el estatus laboral empleado en 42 .5% y la escolaridad secundaria en 54,4%. Entre los factores predisponentes a la infección: el número de parejas sexuales mayor de 2 en el 92%, la preferencia sexual bisexualidad 58%, la preferencia homosexual en el 25,2 % de las personas privadas de la libertad, el tiempo de detección de la infección fue mayor a 3 años en el 54.5 %. En cuanto a hábitos tóxicos: el hábito alcohólico en el 12%, el tabáquico en el 52%, el cafeico en el 78% y la adicción a las drogas en el 12 %. El esquema terapéutico predominante en el 95.2% de los pacientes incluye Tenofovir + Efavirenz + Emtricitabina, la causa principal de cambio fue la resistencia. Las causas de no adherencia terapéutica identificadas son: accesibilidad y disponibilidad del tratamiento, lejanía de la farmacia, costo del transporte.&#x0D; Conclusiones: En los aspectos sociodemográficos se evidenció que predominó: el sexo masculino, la raza mestiza, el grupo de edad de 35-45 años, el estatus laboral empleado y la escolaridad secundaria. En cuanto a los factores predisponentes a la infección por el VIH se constató: el número de parejas sexuales mayor de 2, la bisexualidad y en el caso de las personas privadas de la libertad la preferencia homosexual, el tiempo de detección de la infección superior a 3 años y entre los hábitos tóxicos: la adicción al alcohol, café, tabaco y drogas. Predominó el esquema terapéutico combinado (Tenofovir+Efavirenz+Emtricitabina), la principal causa de cambio fue la resistencia, la mayoría de los pacientes considera que el tratamiento ha mejorado su calidad de vida. Las causas de no adherencia terapéutica identificadas son: accesibilidad y disponibilidad del tratamiento, lejanía de la farmacia y costo del transporte.

Is HIV-1 viraemia below 20 copies/mL in antiretroviral-treated patients associated with virologic outcome?

Background: We aimed to investigate whether very low-level HIV-1 viraemia (VLLV) <20 copies/mL in HIV-1-infected patients on antiretroviral therapy (ART) whose VL was <20 copies/mL, was associated with a subsequent VL > 20 copies/mL.Methods: VLLV was defined as VL <20 copies/mL and positive HIV-1-PCR. We compared patients with positive and negative HIV-1-PCRs <20 copies/mL at two time points, T0 and T1, after 21st of January 2016. Factors associated with a VLLV and subsequent VL >20 copies/mL were identified by logistic regression models.Results: Of 1341 participants at T0, 958 (71.4%) had a negative and 383 patients (28.6%) had positive HIV-RNA PCR signal during VL < 20 copies/mL. The negative relative to the positive signal at T0 was independently associated with dolutegravir (DTG) mono and/or DTG-lamivudine dual therapy (compared to nevirapine), a pre-ART-VL of 1000–9999 copies/mL (compared to ≥100,000 copies/mL), and each additional year of virologic suppression. Having a virolologic outcome at T1 of 20 copies/mL was independently associated with prior positive signal at T0. (OR = 2.291, 95% CI = 1.457–3.601, p value < .001), a past ART interruption, and a change in ART regimen during follow-up. Each additional year of virologic suppression was independently associated with a lower risk for a subsequent VL ≥ 20 copies/mL.Conclusions: A positive HIV-1 RNA PCR <20 copies/mL at T0, was associated with a subsequent VL ≥ 20 copies/mL at T1. This was not a rare phenomenon among patients with VL <20 copies/mL. In most patients with a positive PCR signal, this was not followed by a clinically relevant HIV-1 viraemia, defined as ≥ 200 copies/mL.

CONCOMITANT SEXUALLY TRANSMITTED DISEASES IN PATIENTS WITH DIAGNOSED HIV/AIDS: A RETROSPECTIVE STUDY.

Background:Human immunodeficiency virus (HIV) is a virus that causes Acquired Immunodeficiency Syndrome (AIDS) which weaken the human immune system and thus increasing the incidence of sexually transmitted infections (STIs) and vice versa.Materials and Methods:A retrospective study of STIs in HIV/AIDS patients in Unit Perawatan Intermediate Penyakit Infeksi (UPIPI) Dr. Soetomo General Hospital Surabaya was conducted from January 1st, 2013 to December 31st, 2014. We examined the number and type of STIs, age distribution, gender, occupation, number of CD4+, and antiretroviral treatment of patients with HIV/AIDS. The data were presented in a descriptive analysis.Results:The percentage of STIs patients was 4.2% (148 of 3.350) of all patients with HIV/AIDS in the UPIPI Outpatient Clinic of Dr. Soetomo General Hospital. Most patients were 25-44 years old (70.9%) including 54.7% were males, 8.0% were housewives, and 1.4% were students. The five highest prevalence of STIs were condylomata acuminate (43.9%), non-specific genital ulcers (11.5%), syphilis (10.7%), genital herpes (10.1%), and scabies (8.1%). The sexual predilections consisted of heterosexual (70.9%), homosexual (12.2%), bisexual (2.0%), and no data (14.9%). Patients with the number of CD4+ <200 mm3 was 52.0% and 79.1% of the patients received ARV therapy.Conclusion:STIs and HIV/AIDS were closely related. HIV/AIDS could increase the incidence of STIs and STIs could elevate HIV/AIDS.