Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia

through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm 3 . During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm 3 and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV

Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals-Results from the EuroSIDA study.

OBJECTIVES Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12

Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015

Background: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. Aim: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends. Methods: In three cross-sectional analyses in 2004—05, 2009—10 and 2014—15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression. Results: Overall, the percentage of people on ART increased from 2004—05 (67.8%) to 2014—15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004—05, 87.7% in 2014—15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014—15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014—15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13—0.21) in Eastern Europe. Conclusions: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006–2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006–2007, 7.54 [6.59, 8.59] in 2020–2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63–3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods: HICs were identified in COHERE on the basis of \ue2\u89\ua55 consecutive viral loads (VL) \ue2\u89\ua4500 copies/mL over \ue2\u89\ua51 year whilst ART-naive, with the last VL \ue2\u89\ua4500 copies/mL measured \ue2\u89\ua55 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL &gt;2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs

Cascade of care among HIV patients diagnosed in 2013 in Georgia: Risk factors for late diagnosis and attrition from HIV care

Introduction: The major challenge in the HIV epidemic in Georgia is a high proportion of undiagnosed people living with HIV (estimated 48%) as well as a very high proportion of late presentations for care, with 66% presenting for HIV care with CD4 count 36). In addition, CD4 count at diagnosis (cells/mm 3 ) (≤350 or >350) together with all above factors were tested for the association with attrition through Poisson regression. Results: Overall, 317 patients retained in care, representing 65% of those diagnosed (n = 488). Out of eligible 295 patients, 89.5% were on treatment and 84% of those viral load count was measured after 6 months of antiretroviral treatment initiation had HIV-1 viral load <1000 copies/mL. Patients reporting injecting drug use as a route-of HIV transmission had two times the odds (95% confidence interval = 1.34–3.49) to be diagnosed late and patients reporting male-to-male contact as a way of HIV transmission had half the odds (odds ratio = 0.46 (95% confidence interval = 0.26–0.81)) of late diagnosis compared to patients acquiring HIV through heterosexual contact. Patients older than 36 years were more likely to being diagnosed late. Conclusion: More attention should be given to injecting drug users as they represent the most at-risk population for late diagnosis together with older age and attrition

Effect of remdesivir on mortality and the need for mechanical ventilation among hospitalized patients with COVID-19: real-world data from a resource-limited country

Objectives: Georgia introduced remdesivir for the treatment of COVID-19 in December 2020. We evaluated the real-world effect of remdesivir on mortality and the need for mechanical ventilation among inpatients with COVID-19. Methods: The study included 346 remdesivir recipients and 346 controls not receiving remdesivir selected through propensity score matching based on age, gender, presence of any chronic comorbid condition, and oxygen saturation at admission. Factors associated with in-hospital mortality and the need for mechanical ventilation were assessed in a multivariable logistic regression model. Results: The groups were comparable by age, gender, comorbidities, and baseline oxygen saturation. Among 346 remdesivir recipients, 265 (76.6%) received a generic formulation of the drug. Eight (2.3%) patients died in the remdesivir group and 18 (5.2%) in the control group (P = 0.046). In the multivariable analysis, remdesivir was associated with non-statistically significant reduced odds of death (odds ratio: 0.39, 95% confidence interval: 0.14-1.04, P = 0.06). Significantly fewer patients in the remdesivir group required mechanical ventilation compared to controls: 2.9% vs 6.4% (P = 0.03). Statistically significant difference was maintained in multivariable analysis (odds ratio: 0.40, 95% confidence interval: 1.04-5.60, P = 0.04). Conclusion: Borderline reduction in the odds of death and statistically significant decrease in the need for mechanical ventilation support use of remdesivir in hospitalized patients with COVID-19