SPECTRUM OF DISEASE, MANAGEMENT, EFFICIENCY, CLINICAL PROFILE AND OUTCOMES OF RETROVIRAL DISEASE PATIENTS

HIV is a virus that targets and alters the immune system, increasing the risk and impact of other infections and diseases. Without treatment, the infection might progress to an advanced disease stage called AIDS. A prospective study was conducted for a period of 6 months in a tertiary care hospital with the sample size of 102 patients. A data collection form was taken, which includes the details of demographics date of visit to the hospital, diagnosis, past and current medication history. 102 Inpatients and Outpatients diagnosed with HIV were considered. For the management of HIV, 52 % of 2 NRTI and 1 NNRTI combination and 35 % of 2 NRTI and 1 integrase inhibitor combination were used. The drug usage pattern was found to be tenofovir 74.5 %, lamivudine 83.3 % and Efavirenz 50.9 %. The percentage of subjects with opportunistic infections was 66.6 % and, among these opportunistic infections, tuberculosis was found to be 47.05 %. The viral load after 6 months of ART was found to be undetectable in 95.09 % patients. The levels of CD4 counts were raised after initiation of the ART in 6 months of duration. The death rate was found to be 4.90 %. Due to highly active antiretroviral therapy and effi cient opportunistic infection management, the patients had elevated CD4 levels and undetectable viral load. Hence HAART is highly effi cient in management of HIV which ultimately improves the quality of life of patients.

Quantum Mechanical-Based Stability Evaluation of Crystal Structures for HIV-Targeted Drug Cabotegravir

The long-acting parenteral formulation of the HIV integrase inhibitor cabotegravir (GSK744) is currently being developed to prevent HIV infections, benefiting from infrequent dosing and high efficacy. The crystal structure can affect the bioavailability and efficacy of cabotegravir. However, the stability determination of crystal structures of GSK744 have remained a challenge. Here, we introduced an ab initio protocol to determine the stability of the crystal structures of pharmaceutical molecules, which were obtained from crystal structure prediction process starting from the molecular diagram. Using GSK744 as a case study, the ab initio predicted that Gibbs free energy provides reliable further refinement of the predicted crystal structures and presents its capability for becoming a crystal stability determination approach in the future. The proposed work can assist in the comprehensive screening of pharmaceutical design and can provide structural predictions and stability evaluation for pharmaceutical crystals.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus

Background Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood. Methods This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting. Results Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ± 1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4–1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0–1.9) and waist circumference (+3.6cm; 95% CI, 2.6–4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9–4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2–1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension. Conclusions Differences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed.

879. Evaluation of the Incidence of Hypertension, Diabetes, and Hyperlipidemia in Patients on Antiretroviral Therapy

Background Although integrase inhibitor (INSTI)-based regimens have been associated with weight gain, there is limited data on whether INSTIs cause long-term metabolic consequences. This study evaluated the effect of INSTIs on the development of metabolic comorbidities compared to non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based therapies in patients in the Illinois Department of Corrections. Methods This retrospective cohort study consisted of incarcerated adult patients living with HIV and receiving a guideline-recommended regimen between 7/12/10 and 12/31/19. Patients with a pre-existing diagnosis of diabetes, hypertension, or hyperlipidemia, or lack of medical follow-up data were excluded. The primary outcome was to compare the incidence of a metabolic comorbidity between regimens. Secondary outcomes compared the incidence of weight gain, diabetes, hypertension, and hyperlipidemia as separate outcomes between drug classes. Demographics and pertinent labs were collected. Data was analyzed with ANOVA, chi-squared, and paired t-tests. The primary outcome was adjusted for age, race, use of antipsychotic medications, and family history of metabolic comorbidities. Results A total of 206 patients were included in the analysis with mean follow-up time of 31.5 ± 19.4 months. Majority of patients were Black (69%) and male (91%). A total of 42 patients developed a metabolic comorbidity (Table 1). After adjustment for confounding factors, there was a significant difference in the development of comorbidities between the treatment groups (p=0.031) with INSTI use being more likely to develop a comorbidity than NNRTI (p=0.004). No difference was found between INSTI and PI use (p=0.518). Development of hypertension was significantly higher in the INSTI group than NNRTI group (p=0.014), while the development of diabetes and hyperlipidemia were not. Weight and BMI were significantly higher regardless of antiretroviral (Table 2). No differences were found in the primary outcome between agents within the same drug class or between 1st or 2nd generation INSTIs. Table 1. Results of Primary and Secondary Outcomes Table 2. Impact of HIV regimen on weight and BMI after 1 year Conclusion All antiretrovirals were linked to weight gain but INSTIs were associated with increased incidence of hypertension. Disclosures All Authors: No reported disclosures

903. A Real-world Study Assessing the Risk of Lipid Changes and Other Metabolic Effects Associated with Integrase Inhibitor-based Antiretroviral Therapy

Background Integrase inhibitor (INSTI)-based antiretroviral therapies (ART) are first-line for HIV infection. Recent studies have identified metabolic complications of INSTI regimens, especially when TAF is included. The objective of this study was to assess lipid changes associated with INSTI-based ART. Methods This was a retrospective, observational, single-center study. Patients age ≥ 18 with HIV infection, receiving care Jan 2004 to Jul 2019, and prescribed the same ART for ≥ 6 consecutive months were randomly selected from a computer-generated list. Unique ART regimens prescribed per patient were considered “exposures”. Patients were followed up to 2 years per exposure. INSTI-based exposures included an INSTI plus one or more NRTI. Non-INSTI-based exposures included a PI or NNRTI plus one or more NRTI. Lipid panel results were recorded before and during exposures. Lipid changes with INSTI and non-INSTI exposures were compared. Other metabolic outcomes were recorded. Results 192 exposures were identified (99 INSTI, 93 non-INSTI) among 132 patients. The majority were Black (69.3%) and male (61.9%). Mean age and BMI were 42.0 ± 11.3 and 26.2 ± 5.5 kg/m2, respectively. 72 (37.5%) were ART-naïve. 53.5% INSTI recipients received BIC or DTG. Hypertriglyceridemia (HTG) occurred more often during INSTI exposures (13.1% vs 4.3%; p = 0.031). Mean change in TG concentration was +10.1 and -15.0 mg/dL for INSTI and non-INSTI regimens, respectively (p = 0.105). Patients receiving INSTIs were more commonly prescribed a new lipid-lowering therapy (LLT) or an increase in dose of preexisting LLT (14.1% vs 2.2%; p = 0.003). Of those that received an INSTI-regimen and either TAF, TDF, or no tenofovir, 17.4%, 10.3%, and 8.3% developed HTG, respectively (p = 0.49). There was no difference between groups in HDL or LDL changes. Among INSTI and non-INSTI groups, weight increased by +3.8 and +2.1 kg, respectively (p = 0.129). Mean weight change was less in INSTI recipients whose regimen included TDF (+1.4 vs +4.8 kg; p = 0.053). Conclusion Treatment with INSTI-based ART was associated with HTG. LLTs were utilized more often among INSTI recipients, and this limited our ability to fully characterize lipid changes in this real-world study. Weight gain among INSTI recipients may be attenuated if TDF is included in the regimen. Disclosures James Johnson, PharmD, FLGT (Shareholder) Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member)