Effects of first antiretroviral regimen on lipid levels in HIV (+) individuals

Objective: To evaluate the long-term effects of different boosted protease inhibitors (bPIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral regimens on lipid levels in HIV seropositive individuals who have not received lipid-lowering agents. Methods: Data consisted of 595 patients participating in the population-based Athens Multicenter Cohort Study who were consistently followed up during 1996-2008. Results: In naive patients, lipid parameters increased sharply during the first 3 months of antiretroviral therapy and reached a plateau level approximately 6-9 months after therapy initiation. The plateau levels remained almost stable for up to 3.5 years. In general, bPIs exerted a more pronounced effect compared to NNRTIs. Conclusions: The administration of PI-or NNRTI-based regimens especially in naive but also in unboosted PI experienced patients provoked a sharp increase in lipid levels that remained stable in higher levels for more than 3 years

The HIV patient profile in 2013 and 2003: Results from the Greek AMACS cohort

Combined Antiretroviral therapy (cART) has improved life-expectancy of people living with HIV (PLHIV) but as they age, prevalence of chronic non-AIDS related comorbidities may increase. We study the evolution of HIV-disease markers and comorbidities’ prevalence in PLHIV in Greece. Two cross-sectional analyses (2003 and 2013) on data from the AMACS cohort were performed. Comparisons were based on population average models and were repeated for subjects under follow-up at both 2003 and 2013. 2,403 PLHIV were identified in 2003 and 4,910 in 2013 (1,730 contributing for both cross-sections). Individuals in 2013 were on average older, diagnosed/treated for HIV for longer, more likely to be on cART, viro-logically suppressed, and with higher CD4 counts. Chronic kidney disease, dyslipidemia and hypertension prevalence increased over time. There was an increase in prescription of lipid-lowering treatment (3.5% in 2003 vs. 7.7% 2013, p<0.001). Among 220 and 879 individuals eligible for Framingham 10-year Event Risk calculation, the proportion of patients in the high-risk group (>20%) increased from 18.2% to 22.2% (p = 0.002). Increase in the prevalence of comorbidities was more pronounced in the subset of patients who were followed in both 2003 and 2013. The increased availability and uptake of cART led to significant improvements in the immuno-virological status of PLHIV in Greece, but they aged alongside an increase in prevalence of non-AIDS related comorbidities. These results highlight the need for appropriate monitoring, optimal cART selection and long-term management and prevention strategies for such comorbidities. © 2018 Pantazis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Inequalities by educational level in response to combination antiretroviral treatment and survival in HIV-positive men and women in Europe

Background: Socioeconomic inequality challenges population-level implementation of health interventions. We investigated differences by educational level in clinical, virological, and immunological responses to combined antiretroviral treatment (cART) in HIV-positive men and women in Collaboration of Observational HIV Epidemiological Research in Europe, a European collaboration. Methods: Data were pooled from 15 cohorts in eight countries of patients initiating cART in 1996-2013 with data on educational level categorized in UNESCO/ISCED classifications. Kaplan-Meier curves, Cox and piecewise linear mixed models were used. Results: Of 24 069 HIV-positive patients, 9% had not completed primary education, 32% had completed primary, 44% secondary, and 15% tertiary education. Overall, 21% were women, who were overrepresented in lower educational strata. During 132 507 person-years of follow-up, 1081 individuals died; cumulative mortality decreased with higher educational level (P< 0.001). Over 122 765 person-years, new AIDS events or death occurred in 2598 individuals; differences by education were more marked than for death alone (P< 0.001). Virological response was achieved by 67% of patients without completed basic education, 85% with completed primary education, 82% with secondary, and 87% with tertiary (P< 0.001). Patients with higher education had higher CD4(+) cell count at cART initiation and at each time after cART but rate of CD4(+) cell count recovery did not differ. Differences in mortality and clinical responses were similar for men and women and were not entirely explained by delayed HIV diagnosis and late cART initiation. Conclusion: HIV-positive patients with lower educational level had worse responses to cART and survival in European countries with universal healthcare. To maximize the population impact of cART, Europe needs to decrease the socioeconomic divide. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Transmission dynamics of HIV-1 drug resistance among treatment-naïve individuals in Greece: The added value of molecular epidemiology to public health

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was &amp;gt;1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was &amp;gt;1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was &amp;gt;1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health. © 2017 by the authors. Licensee MDPI, Basel, Switzerland

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003–2015: Transmitted drug resistance is due to onward transmissions

Background The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. Methods HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003–30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. Results The proportion of sequences with SDRMs was 5.98% (n = 205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. Conclusions The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients. © 2017 Elsevier B.V

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece

Objectives Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. Methods Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. Results A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. Conclusions Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

Dating the Origin and Estimating the Transmission Rates of the Major HIV‐1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infec-tions/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV‐1 outbreak ten years ago in Athens, Greece. Transmission rate can be consid-ered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

A nationwide study about the dispersal patterns of the predominant HIV-1 subtypes A1 and B in Greece: Inference of the molecular transmission clusters

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2–1518 subtype A1 sequences and 168 MTCs in the range of 2–218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p &lt; 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p &lt; 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p &lt; 0.001), and more recent sampling (time period: 2011–2015 vs. 1999–2005, OR = 3.83, p &lt; 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

HIV continuum of care: Bridging cross-sectional and longitudinal analyses

Objective: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. Design: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability. Methods: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-followup (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound. Findings: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980 - 2018). Median time to diagnosis was 3.5 years (IQR: 1.1 - 7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years. Interpretation: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved