Treatment-naive HIV Patients Research Articles

Prevalence of Opportunistic Infections in Treatment-Naive HIV Patients in a Secondary Care Center.

Introduction HIV-related immunosuppression significantly increases the risk of contracting opportunistic infections (OI) due to bacteria, viruses, fungi, and protozoa. This study estimates the prevalence of opportunistic infections in HIV patients who have not received previous antiretroviral therapy (ART) in the second-largest hospital in Honduras. Methods This retrospective observational study analyzed the medical records of the treatment-naive HIV patients who attended the Mario Catarino Rivas National Hospital in Honduras in all of 2023. The data collected was on demographics and clinically or laboratorially diagnosed opportunistic infections of 110 patients. Results The overall prevalence of OIs among the 110 treatment-naive HIV patients was 31 (28.2%). The most frequent OIs were: cryptococcosis 9/31 (29.0%), candidiasis 8/31 (25.8%), tuberculosis 6/31 (19.4%), toxoplasmosis 4/31 (12.9%), pneumocystis 3/31 (9.7%), and histoplasmosis 2/31 (6.5%). Most patients with at least one OI had a viral load >100,000 copies/mL and a CD4+ cell count <200 cells/mm3. Conclusion There has been an increase in the prevalence of fungal IOs in treatment-naive HIV patients in Honduras. Adequate allocation of resources for the diagnosis and treatment of these in the country's healthcare system is paramount.

Transmitted drug resistance and molecular transmission network among treatment-naive HIV-1 patients in Wenzhou, China, 2020–2023

BackgroundTransmitted drug resistance (TDR) increases the risk of antiretroviral therapy (ART) failure in HIV-1 patients. This study investigated the molecular epidemiology of TDR and its transmission networks among newly diagnosed HIV-1 patients in Wenzhou, China.MethodsWe enrolled 1878 ART-naive HIV-1 patients from January 2020 to October 2023. TDR was evaluated using the Stanford University HIV Drug Resistance Database. We performed phylogenetic analysis, genotyping, transmission clustering, and population-based TDR-related factor analysis.ResultsAmong 1782 patients with successful genotyping, TDR prevalence was 5.7%. Multivariable analysis identified CRF08_BC subtype (adjusted odds ratio [aOR] 18.59, 95% CI 3.79-336.18, p = 0.004), CD4 > 500 cells/mm³ (aOR 2.19, 95% CI 1.16–4.03, p = 0.013), and year 2023 (aOR 1.83, 95% CI 1.11–4.89, p = 0.039) as factors associated with higher TDR risk. The most prevalent NNRTI mutations were K103N, E138A, and V179E. Seven TDR transmission clusters were identified, notably one with V179D that expanded during 2020–2023.ConclusionsWhile TDR prevalence in Wenzhou remained lower than in other Chinese regions, an upward trend was observed. Most resistant individuals were in transmission clusters, predominantly middle-aged and elderly. NNRTI resistance was severe and concentrated in efavirenz, nevirapine, and rilpivirine. Enhanced HIV surveillance and wider free antiretroviral options are crucial to control drug-resistant HIV spread in Wenzhou.

Study of Inflammatory Biomarkers in Treatment-Naive HIV Patients and Their Correlation With Clusters of Differentiation 4 (CD4) Count.

Introduction The human immunodeficiency virus (HIV) primarily targets clusters of differentiation 4 (CD4)+ T cells and other immune cells, leading to immune dysfunction. Cytokines such as interleukin (IL)-23 and IL-27 have complex roles in HIV-associated disease progression, affecting viral replication and immune responses. This study aimed to explore the correlation between HIV-related CD4 lymphopenia and the inflammatory cytokines IL-23 and IL-27 in treatment-naive HIV patients. Materials and methods This is a single-center, prospective, observational study conducted at the Antiretroviral Treatment (ART) Center of Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India. Sixty-five treatment-naive HIV seropositive patients were recruited in this study. Quantitative estimation of inflammatory biomarkers (IL-23 and IL-27) was performed using enzyme-linked immunosorbent assay (ELISA). The fluorescent-activated cell sorter count (FACSCount) technology was used to determine the CD4+ T-cell count. Results Our study revealed that HIV-infected individuals had significantly higher levels of IL-23 (868.9±246.7 pg/mL vs 98.3±86.6 pg/mL, p < 0.01) and IL-27 (1629.5±518.5 pg/mL vs 291.3±225.2 pg/mL, p < 0.01) compared to healthy controls. Additionally, we found a strong positive correlation between CD4 count and IL-23 titers (r = 0.93, p < 0.01), as well as between CD4 count and IL-27 titers (r = 0.92, p < 0.01) in HIV-positive individuals. Conclusion The findings suggest that these cytokines respond to HIV infection and may potentially play a crucial role in restraining HIV replication and slowing down the progression of the disease.

High risk APOL1 genotypes and kidney disease among treatment naïve HIV patients at Kano, Nigeria.

Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country. DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve. The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group. This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.

Cytopenias in Treatment-naive HIV Patients: A Comparison of Turkey and Somalia

Cytopenias in Treatment-naive HIV Patients: A Comparison of Turkey and Somalia

Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China

Abstract Background With the high prevalence of pre-treatment drug resistance (PDR) and the potential impact to the virological inhibition, the detection of PDR was particularly necessary. This study aimed to determine the prevalence of PDR in Guangdong, China, and its impact on antiretroviral therapy (ART) in treatment-naive HIV patients. Methods A retrospective cohort study was conducted. A total of 1936 HIV-1–infected treatment-naive patients in the clinic of the infectious department, Guangzhou Eighth People’s Hospital, between August 2018 and December 2019 were assayed for PDR mutations before initiating ART. Patients with PDR mutations (PDR arm) were screened and compared with those without drug-resistant mutations (non-PDR arm). The rate of HIV-1 virologic failure (VF) and CD4+ T-cell counts of the 2 arms were compared at the 96th week after ART to evaluate the impact of PDR on the efficacy of ART. Results Pretreatment drug resistance was detected in 125 cases (6.46%) from the 1936 enrolled participants, most of which were resistant to non-nucleoside reverse transcriptase inhibitors (64.00%, 80/125). One hundred and eight of 125 completed the follow-up of 96 weeks (PDR arm). In this cohort, 52 patients whose ART regimen containing the resistant drug were grouped as con-PDR arm, and the remaining 56 patients whose ART regimen did not contain the resistant drug were grouped as non- con-PDR arm. A total of 125 patients without PDR were randomly selected as the control group (non-PDR arm), 112 of whom had completed the 96-week follow-up. At the 96th week after ART initiation, 7 patients (6.5%, 7/108) in the PDR arm and 1 patient (0.9%, 1/112) in the non-PDR arm developed VF, exhibiting a significant difference (χ 2 = 4.901, P = 0.029). Meanwhile, 3 patients (5.8%, 3/52) in the con-PDR arm developed VF; the rate was also higher than that in the non-PDR arm, but without a significant difference (χ 2 = 3.549, P = 0.095). The CD4+ T-cell count in the non-PDR arm increased more than the PDR arm (386.6 vs. 319.1 cells/μL, t = 2.448, P = 0.015) or the con-PDR arm (386.6 vs. 325.1 cells/μL, t = 1.821, P = 0.070) at 12 weeks after ART. However, no significant differences were observed in the CD4+ T-cell count from the 24th week after ART onward. Conclusions Pretreatment drug resistance was moderately prevalent in Guangdong, China, and could affect the antiretroviral efficacy during a 96-week observation period, indicating the need to closely monitor PDR before ART initiation.

Social Network Dynamics in Transmission of HIV by Sexual Contact

According to statistics published by the Joint United Nations Programme on HIV/AIDS (UNAIDS), by the end of 2019, 38 million people were living with HIV. Hornet is the most frequently-used gay-oriented social network worldwide, especially in France, Russia, Brazil, Turkey, and Taiwan. In this study, we focused on the correlation between the route of transmission for the HIV-1 virus and social media application usage in terms of sexual contact according to the generation category in Turkey. The study included 280 heterosexual, bisexual, and men who have sex with men (MSM) who were newly diagnosed and antiretroviral treatment-naive HIV-1 patients from cities located in the Marmara region in Turkey. Face-to-face interviews were conducted with each patient between 2015 and 2020. As key populations of the study, bisexuals and MSMs were counted together in the MSMs category because in both sexual preferences, MSM. HIV-1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis. Subtype B (80%, 224/280), non-subtype B (7.5%, 21/280), and CRFs (12.5%, 35/280) were identified as the most commonly occurring HIV-1 subtypes. HIV-1 acquisition route was found to be largely through MSM contact (67.9%, 190/280) compared to heterosexual contact (32.1%, 90/280). We have analysed the role of sex-oriented social media applications in HIV transmission among different sexual contacts. The study results showed that sex-oriented social media applications play a facilitator role in HIV transmission between key populations. This study may be useful for developing policies to prevent HIV transmission.

Increase in bone turnover markers in HIV patients treated with tenofovir disoproxil fumarate combined with raltegravir or efavirenz

IntroductionAccelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens. MethodsA prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group. ResultsIn both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment. ConclusionsTreatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.

Short Communication: Trends in Transmitted Drug Resistance in Treatment-Naive HIV Patients in Korea.

Transmitted drug resistance (TDR) in treatment-naive HIV patients can contribute to failure of initial antiretroviral therapy. In Korea, there has been a gradual increase in TDR, but the recent increase in the use of integrase strand transfer inhibitors (INSTIs) could affect TDR trends and INSTI resistance mutations. We evaluated the patterns of TDR in newly diagnosed HIV patients over time from 2011 to 2019. We analyzed the genotypic resistance of strains in 336 patients and sequenced the integrase gene in 71 among 336 subjects. The overall prevalence of TDR was 5.9% (20 of 336 patients), and it showed a tendency to increase over time (5.1% in 2011-2013, 6.1% in 2014-2016, and 7.2% in 2017-2019; p = .3018). Furthermore, non-nucleoside reverse transcriptase inhibitor resistance showed a marginally significant increase over time (1.45% in 2011-2013, 3.48% in 2014-2016, and 6.02% in 2017-2019; p = .0505). Regarding transmitted INSTI resistance mutation, there were no major INSTI resistance mutations but several accessory INSTI resistance mutations and predominant natural polymorphisms. This study shows several significant changes in TDR and suggests the importance of continuous surveillance of TDR and genetic variation in the integrase region.

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.

ObjectiveTo assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients.MethodsWe performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/μL, not starting c-ART; and group B, CD4<500 cells/μL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time.ResultsThe study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30–43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values.ConclusionsIn treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

Galectin-9 and VISTA Expression Define Terminally Exhausted T Cells in HIV-1 Infection.

We report significant upregulation of Galectin-9 (Gal-9) and VISTA on both CD4+ and CD8+ T cells in HIV-infected human patients. Gal-9 and VISTA expression was associated with impaired T cells effector functions. Although Gal-9 was coexpressed with other coinhibitory receptors such as TIGIT, CD160, CD39, and VISTA, it was simultaneously coexpressed with PD-1. Coexpression of Gal-9 with PD-1 was associated with a more terminally exhausted T cell phenotype in HIV-1 patients. This was marked by higher expression of EOMES, blimp1, and Glut1 in Gal-9+ versus Gal-9- T cells, which is consistent with an exhausted T cell phenotype. Gal-9+ T cells exhibited the phenotype characteristics of effector T cells (CD45RA+, CD45RO-/lo, CD62L-, CD27lo) with higher T-bet expression. A positive correlation between the plasma viral load with the plasma Gal-9 levels in treatment-naive HIV patients and an inverse correlation between CD4 count with the frequency of CD4+Gal-9+ T cells were observed. Increased percentages of Gal-9+ T cells was evident in HIV-treated patients. Enhanced expression of Gal-9 on T cells following PMA stimulation via protein kinase C suggests persistent TCR stimulation as a potential contributing factor in Gal-9 upregulation in HIV patients. This was supported by the constant degranulation of Gal-9+ T cells. Moreover, CD44 clustering by Gal-9 may influence cytoskeleton rearrangement and coclustering of CD3, which likely impact initiation of signal transduction via TCR. Our preliminary data also confirm upregulation of Gal-9 on T cells in hepatitis B virus and HPV infections. These results demonstrate a novel role for Gal-9 and VISTA in HIV pathogenesis.

Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block

ABSTRACT Opportunistic bacterial infections amongst HIV–infected individuals contribute significantly to HIV-associated mortality. The role of HIV-mediated modulation of innate mechanisms like autophagy in promoting opportunistic infections, however, remains obscure. Here we show, HIV reactivation in or infection of macrophages inhibits autophagy and helps the survival of pathogenic Mycobacterium tuberculosis (Mtb) and nonpathogenic non-tuberculous mycobacterial strains (NTMs). The HIV-mediated impairment of xenophagy flux facilitated bacterial survival. Activation of autophagy by trehalose could induce xenophagy flux and kill intracellular Mtb or NTMs either during single or co-infections. Trehalose, we delineate, activates PIKFYVE leading to TFEB nuclear translocation in MCOLN1-dependent manner to induce autophagy. Remarkably, trehalose significantly reduced HIV-p24 levels in ex–vivo-infected PBMCs or PBMCs from treatment-naive HIV patients and also controlled mycobacterial survival within Mtb-infected animals. To conclude, we report leveraging of HIV-mediated perturbed host innate-immunity by opportunistic bacterial pathogens and show an attractive therapeutic strategy for HIV and associated co-morbidities. Abbreviations: AIDS: acquired immune deficiency syndrome; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; BafA1: bafilomycin A1; CFU: colony forming unit; CTSD: cathepsin D; CD63: CD63 molecule; EGFP: enhanced green fluorescent protein; FRET: Förster resonance energy transfer; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GLUT: glucose transporter; HIV: human immunodeficiency virus; hMDMs: human monocyte derived macrophages; IL2: interleukin 2; LAMP1: lysosomal-associated membrane protein 1; LC3B-II: lipidated microtubule-associated proteins 1A/1B light chain 3B; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin; mRFP: monomeric red fluorescent protein; M6PR: mannose-6-phosphate receptor; NAC: N- acetyl- L –cysteine; NTM’s: non-tuberculous mycobacteria; PBMC: Peripheral Blood Mononuclear cells; PIKFYVE: phosphoinositide kinase; FYVE-Type Zinc Finger; PHA: phytohemagglutinin; PMA: phorbol 12-myristate 13-acetate; PtdIns(3,5)P2: Phosphatidylinositol 3,5-bisphosphate; ptfLC3: pEGFP-mRFP-LC3; ROS: reactive oxygen species; SQSTM1: sequestosome1; TFEB: transcription factor EB; MCOLN1/TRPML1: mucolipin 1; PIP4P1/TMEM55B: Human trans-membrane Protein 55B; UVRAG: UV Radiation Resistance Associate; VPS35: vacuolar protein sorting associated protein 35; WDR45: WD repeat domain 45; YCAM: Yellow Chameleon.

Impact of Population and Pharmacogenetics Variations on Efavirenz Pharmacokinetics and Immunologic Outcomes During Anti-Tuberculosis Co-Therapy: A Parallel Prospective Cohort Study in Two Sub-Sahara African Populations.

Efavirenz-based combination antiretroviral-therapy (cART) is the recommended regimen during tuberculosis (TB) therapy. In a multi-national parallel prospective-cohort study, we investigated the impact of population and pharmacogenetic variations for efavirenz pharmacokinetics, auto-induction, and immunologic outcome during antituberculosis treatment. A total of 921 treatment-naïve HIV patients with (196 Ethiopians and 231 Tanzanians) or without TB co-infection (285 Ethiopians and 209 Tanzanians) were enrolled and treated with efavirenz-based cART. TB-HIV patients started rifampicin-based anti-TB therapy 4 weeks before cART. Efavirenz plasma concentrations were measured on the 4th and 16th weeks of cART. Genotyping for CYP2B6, CYP3A5, ABCB1, UGT2B7, and SLCO1B1 was done. CD4 cells-count was measured at baseline, 12th, 24th, and 48th weeks of cART. Among HIV-only cohort, plasma efavirenz concentration and median CD4 cell count were significantly higher in Tanzanians than Ethiopians, and both CYP2B6 genotype and population-variation were significant predictors of efavirenz plasma concentration. Within-population analyses indicated a pronounced efavirenz autoinduction in Tanzanians as reflected by a significant decrease of plasma efavirenz concentration over time (p = 0.0001), but not in Ethiopians. Among TB-HIV cohort, there were no significant between-population differences in plasma efavirenz concentrations or CD4 cell-recovery, and CYP2B6 genotype but not population-variation was a significant predictor of efavirenz plasma exposure. In Tanzanian patients, short-term anti-TB co-treatment significantly reduced the mean plasma efavirenz concentration in CYP2B6*1/*1 genotype at week-4 (p = 0.005), but not at week-16 of cART. In Ethiopian patients, anti-TB cotreatment increased the mean plasma efavirenz concentration among CYP2B6*6 carriers at week-4 (p = 0.003) and week-16 (p = 0.035) of cART. In general, long-term anti-TB co-treatment increased plasma efavirenz concentration at week 16 of cART in both Ethiopians and Tanzanians being higher in CYP2B6*6/*6 > *1/*6 > *1/*1 genotypes. In TB-HIV patients, baseline body mass index (BMI), viral load, and WHO clinical-stage but not genotype, population-variation, or efavirenz concentration were significant predictors of immunologic outcome at week-48. In summary efavirenz auto-induction, pharmacokinetics, and the immunologic outcome are influenced by population-variation, anti-TB co-medication, and CYP2B6 genotype. CYP2B6 genotype is a significant predictor of efavirenz plasma exposure regardless of population-variation or antituberculosis co-treatment, but population-variation is insignificant during antituberculosis treatment. CYP2B6 genotype, population, and geographic differences need to be considered for efavirenz dosage-optimization.

Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

Hyperglycemia and insulin function in antiretroviral treatment-naive HIV patients in Ethiopia: a potential new entity of diabetes in HIV?

Although diabetes is more common in HIV patients, the direct link between HIV and diabetes is unknown. Glucose abnormalities should be assessed among antiretroviral treatment (ART)-naive patients to reduce confounding by ART. We assessed diabetes status, insulin function and association with inflammation among Ethiopian ART-naive HIV patients. Among HIV patients initiating ART, we used glycosylated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to define prediabetes and diabetes. Insulin during OGTT was determined to calculate insulin function, and C-reactive protein and α1-acid glycoprotein were used as same-day markers of inflammation. Among 332 HIV patients, mean (SD) age was 32.9 (8.8) years, and 222 (66.9%) were women. None had known diabetes, but we found diabetes prevalence using OGTT and HbA1c to be 7.6 and 8.5%, respectively. C-reactive protein and α1-acid glycoprotein were positively associated with hyperglycemia and insulin deficiency, but not insulin resistance. We found poor correlation between traditional risk factors (age and anthropometry) and diabetes, but participants generally had low BMI and waist circumference. ART-naive Ethiopian HIV patients had a high prevalence of prediabetes and diabetes, with a poor agreement between HbA1c and OGTT. Diabetes was associated with inflammation, but not with adiposity and age. Diabetes was linked to insulin deficiency, rather than insulin resistance, which may represent a different entity than type 1 and 2 diabetes. This has implications for choice of drugs, when managing diabetes in African HIV patients.

Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients.

Objective:Compare the efficacy and safety of the 2-drug antiretroviral therapy regimen dolutegravir + lamivudine (DTG + 3TC) with traditional 3-drug regimens in treatment-naive patients with HIV-1.Design:Data from double-blind, randomized controlled trials of at least 48 weeks’ duration in treatment-naive patients with HIV-1 identified by systematic review were evaluated using a Bayesian network meta-analysis methodology.Methods:The primary outcome was virologic suppression at Week 48 for 3-drug regimens versus DTG + 3TC (also analyzed in patient subgroup with baseline viral load >100 000 RNA copies/ml). Secondary outcomes included CD4+ cell count change from baseline and safety (adverse events, serious adverse events, and drug-related adverse events) at Week 48.Results:The network contains 14 unique regimens from 14 randomized controlled trials based on data from 10 043 patients. The proportional difference for viral suppression at 48 weeks for DTG + 3TC versus the other 13 regimens included in the network ranged from −2.7% (−11.0, 5.6%) versus DTG + tenofovir alafenamide/emtricitabine (FTC) to 7.3% (0.6, 13.8%) versus efavirenz + tenofovir disoproxil fumarate/FTC. DTG + 3TC was found to be significantly better than efavirenz + tenofovir disoproxil fumarate/FTC and similar to all other regimens analysed in terms of viral suppression at 48 weeks. With regard to other outcomes (CD4+, adverse event, serious adverse event, drug-related adverse events) at 48 weeks, DTG+3TC was broadly similar to all regimens analysed.Conclusion:This network meta-analysis demonstrates similar efficacy and safety outcomes over 48 weeks with DTG + 3TC compared with traditional 3-drug antiretroviral therapy regimens.

CIRCULATORY CYTOKINES AND HEMATOLOGICAL PROFILES: POSSIBLE BIOMARKERS OF HIV/AIDS DISEASE PROGRESSION

Introduction: This study sought to identify circulatory cytokines and hematological profiles measureable in blood plasma in newly diagnosed HIV patients as possible biomarkers that could predict the progression of HIV and AIDS disease in the course of acute HIV infection. Methodology: A prospective cross sectional study design was used to recruit the participants at the Nakuru Provincial General hospital in Kenya. The study group included those who were HIV positive before and after commencing therapy and those who were HIV negative. The study group composed of male and female of different ages ranging from 7-72 years. Hematology auto analyzer system was used to analyze hematological parameters and indices. Types and concentrations of cytokines were determined using multiplex cytokine immunoassay by flow cytometry using Becton and Dickinsonfluorescence activated cell sorter (BD FACS) count. Descriptive statistics were applied and a p- value < 0.05 was considered statistically significant. Results: This study found a significant difference in mean Interleukin 12p70 (p<0.001), Tumor Necrosis Factor (p<0.05), Interleukin 10 (p<0.05), Interleukin 6 (p<0.005) and interleukin 1β (p<0.05) between HIV negative patients, treatment naive HIV patients and HIV patients on highly active antiretroviral therapy (HAART). Among the treatment naive HIV patients, significant associations were observed between IL-12p70 and HGB (p<0.05); between TNF and MPV (p<0.001); between IL-10 and PDW (p<0.005); between IL-6 and Gran# (p-0.05); between IL-1β and PDW (p<0.005). Conclusion: The early period of infection with HIV is characterized by high circulatory cytokines levels and could be useful biomarkers and indicators of early immune activation of HIV infection. The results from this study also showed that acute HIV infection induces several hematological changes, involving all the blood parameters and indices, some of which may act as indicators of HIV/AIDS disease progression. Article DOI: https://dx.doi.org/10.20319/lijhls.2019.51.105118 This work is licensed under the Creative Commons Attribution-Non-commercial 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA.

Alterations in Serum Zinc and Polyunsaturated Fatty Acid Concentrations in Treatment-Naive HIV-Diagnosed Alcohol-Dependent Subjects with Liver Injury.

Heavy alcohol drinking causes alterations in the metabolism of fatty acids and zinc that participate in inflammation and liver injury. HIV infection has been reported to cause dysregulated polyunsaturated fatty acid (PUFA) and zinc metabolism. In this pilot study, we examined the role of dysregulated PUFA metabolism and zinc deficiency in the liver injury occurring in heavy drinkers with early-stage HIV diagnosis. Fourteen heavy drinking alcohol-dependent (AD) patients [seven with treatment-naive HIV diagnosis (AD+HIV) and seven without HIV infection (AD)] participated in this study. Liver injury, serum zinc, PUFAs, viral load, CD4+ count, and drinking measures using lifetime drinking history (LTDH), and timeline follow-back past 90 days (TLFB90) were evaluated. Liver injury was also assessed in seven age- and gender-matched socially drinking HIV treatment-naive patients who served as disease controls. HIV viral load by itself did not show any correlation with liver injury. Liver enzymes were significantly elevated in both AD+HIV and AD patients, and AD+HIV patients had significantly higher alanine aminotransferase (ALT) levels than did AD patients, even with lower drinking. Serum zinc was significantly lower in AD+HIV patients. Only AD+HIV patients showed a significant elevation in linoleic acid (LA) and alpha-linoleic acid (ALA) levels. Serum zinc and ALT, LA and ALT, and ALA and ALT were significantly associated only in AD+HIV patients. The association between LA and ALT showed a higher effect than did the ALA and ALT association in the AD+HIV patients. Interestingly, AD+HIV subjects (who drank less), nevertheless, showed more liver injury compared with AD patients, who reported heavier drinking. We speculate that the underlying proinflammatory response resulting from zinc deficiency and an elevation in serum LA likely contributed to liver injury in AD+HIV patients, even with a comparatively lower degree of heavy drinking.

Liver Enzyme Abnormalities: A Comparative Study between Treatment Naïve HIV and HIV Negative Hospital Patients

Background and Aims: The prevalence of People living with human Immunodeficiency virus remains considerably high in Nigeria. Liver disease has emerged as an increasingly significant contributor to mortality among HIV-infected patients. The aim of our study was to compare the difference in the prevalence of liver enzyme abnormalities between treatment naive HIV positive and HIV negative patients. Method: The study was conducted at a teaching hospital. The study population consists of 736 patients (368 cases and 368 controls) that were selected from the hospital. The cases were treatment naive HIV patients and the controls were patients being managed for other diseases. A diagnosis of liver disease was made based on the diagnostic criteria which include; presence of at least one clinical feature of liver disease, two liver chemistry abnormalities and an abnormal hepatic ultrasound report. Result: The mean ages of the cases and controls were 35.97±9.77 and 36.08±9.54 years respectively. Liver disease was seen in 277 (75.3%) of the cases and 54 (14.7%) of the controls, this difference was statistically significant (pConclusion: The use of abnormal liver enzymes and clinical features in resource poor settings are valuable screening tools to indicate the presence of liver diseases particularly in HIV – infected patients.

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients