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The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro . However, its efficacy in patients with COVID-19 has not been studied.

Objective To investigate changes in weight following the initiation of antiretroviral therapy in treatment-naive Asian people living with human immunodeficiency virus (PLWH). Methods This retrospective observational study evaluated adult treatment-naive Asian PLWH who started antiretroviral therapy based on an integrase strand transfer inhibitor, a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor at the AIDS Clinical Centre, Tokyo between January 2005 and February 2019. Patients were followed-up until October 2019. Multi-variate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight was reported at 3-month intervals until censoring or for 5 years after treatment initiation. Results Five years after treatment initiation, average weight gain in PLWH who started on dolutegravir-, darunavir- and elvitegravir-based treatment was 5.3 kg, 4.1 kg and 4.6 kg, respectively, while those who started on raltegravir-, lopinavir- and atazanavir-based treatment gained an average of 1.9 kg, 2.1 kg and 2.3 kg, respectively. Average weight gain in PLWH who started treatment with the backbone drugs, tenofovir alafenamide, abacavir and tenofovir disproxil fumarateb was 4.1 kg, 3.0 kg and 3.0 kg, respectively, and those treated with dolutegravir plus tenofovir alafenamide/emtricitabine gained an average of 6.7 kg. Conclusions Antiretroviral-therapy-associated weight gain continued to increase for 5 years following treatment initiation. A combination of dolutegravir and tenofovir alafenamide/emtricitabine was associated with the greatest weight gain.

Background Weight gain after the initiation of antiretroviral therapy (ART) is becoming a major clinical issue in treatment-naïve people living with human immunodeficiency virus (PLWH). However, limited data exist for the Asian populations. We aimed to investigate changes in weight after the initiation of ART therapy in treatment-naïve Asian patients. Methods We evaluated adult, treatment-naïve Asian PLWH who started integrase strand transfer inhibitor (INSTI)-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART at AIDS Clinical Center, Tokyo, between January 2005 and February 2019. They were followed up until October 2019. Multivariate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight by ART class (INSTI, PI, and NNRTI), each key drug (dolutegravir [DTG], elvitegravir [EVG], raltegravir [RAL], and darunavir [DRV]), and each key drug with or without the use of tenofovir alafenamide (TAF)/emtricitabine (FTC) was reported at 3-month intervals until censoring or 5 years. Results Among the 1,579 study patients, 610 (38.6%), 929 (58.8%), and 40 (2.5%) started INSTI-, PI-, and NNRTI-based ART. After 5 years, PLWH who initiated DTG- (5.3 kg), DRV- (4.0 kg), and EVG-based treatment (4.6 kg) gained more weight than those who initiated RAL-based treatment (1.8 kg). PLWH who initiated DTG plus TAF/FTC (6.7 kg) gained the largest weight. Conclusion In the Asian PLWH population, ART-associated weight gain continues to increase for 5 years after treatment initiation. DTG plus TAF/FTC was associated with the largest weight gain. Disclosures All Authors: No reported disclosures

Objectives To determine the mortality and causes of death in people living with HIV (PLHIV) in Japan. Design A prospective cohort study at AIDS Clinical Center, Tokyo, which treats approximately 10% of PLHIV in care in Japan. Methods Either PLHIV who visited our center for the first time between January 2005 and December 2014 or PLHIV who started their regular visit before January 2005 and visited us between January and March 2005 were included and followed by the end of 2016. Causes of death were defined according to the CoDe protocol. Results Two thousand, seven hundred and ninety-seven PLHIV were analysed with total of 18 858 person-years of follow-up, which constitutes 14% of the estimated number of PLHIV in care in Japan. One hundred and sixty-five (5.9%) PLHIV died with all-cause mortality rate of 8.75 per 1000 person-years. All-cause mortality rate for PLHIV in care in Japan was estimated to be 8.75 per 1000 person-years (95% CI 5.53-12.0). Among causes of death, AIDS-defining illnesses accounted for 39% and malignancy contributed to 47%. Standardized mortality ratio (SMR) for all-cause mortality, malignancy-related mortality, and suicide were 5.96 (95% CI 5.05-6.87), 7.76 (95% CI 6.02-9.51), and 3.24 (95% CI 1.54-4.94), respectively. Even among the patients who were diagnosed early or without history of AIDS, SMR was four times higher than the general population. Conclusion Mortality of PLHIV, even among those with early diagnosis, is substantially higher than that of the general population in Japan, highlighting the importance of further efforts towards prevention, early diagnosis and prompt treatment initiation.

The extent and duration of long-term recovery of CD4 count, CD4 percentage (CD4%), and CD4/CD8 ratio after initiation of combination antiretroviral therapy (cART) in patients with a suppressed viral load (VL) are largely unknown.Patients infected with human immunodeficiency virus type 1 who started cART between January 2004 and January 2012 and showed persistent viral suppression (VL,200 copies/mL) for ≥4 years were followed up at the AIDS Clinical Center in Tokyo. Change point analysis was used to determine the time point when CD4 count recovery shows a plateau, and a linear mixed model was applied to estimate the CD4 count at this change point.Data were analyzed from 752 patients (93% male; median age, 38 years; median baseline CD4 cell count, 172/µL [interquartile range CD4%, 13.8%]; CD4/CD8 ratio, 0.23). The median follow-up period was 81.2 months, and 91 patients (12.1%) were followed up for10 years. Change point analysis showed that CD4 count, CD4%, and CD4/CD8 ratio continued to increase until 78.6, 62.2, and 64.3 months, respectively, with adjusted means of 590/µL (95% confidence interval, 29.5%, and 0.89, respectively, at the change point. Although CD4 counts ≥500/μL were achieved in 73.8% of the study patients, they were not achieved in 48.2% of those with a baseline CD4 count100/μL. Neither the CD4% nor the CD4/CD8 ratio were normalized in a majority of patients.The results showed lack of normalization of CD4 count, CD4%, and CD4/CD8 ratio to the levels seen in healthy individuals even after long-term successful cART in patients with a suppressed VL.

Background Although CD4 count is an important marker for prognosis of patients infected with HIV-1, how long and how much CD4 count will increase after initiation of cART are still unknown. Hence, the aim of this study is, using change point analysis, to examine the long-term CD4 count restoration among well-controlled HIV-1 patients. Methods In this single-center cohort study at AIDS Clinical Center, Tokyo, we examined HIV-1 infected patients who initiated cART between January 2004 and January 2012 and achieved HIV viral load of 200 copies/mL, discontinuation of cART for >30 days, lost to follow-up for >1 year, initiating chemotherapy for malignancy, or death), or at end of the observation period (September 30, 2015). Change point analysis was performed to determine the time point where the restoration of CD4 count becomes plateau. Results Of 752 patients, 708 (94.2%) were male and 89.9% was MSM. The median age was 39.3 years [IQR, 32–45] and the median baseline CD4 count and %CD4 were 172 cells/mm3 [IQR, 61–254], and 13.8% [IQR, 7.7–18.5], respectively. The median follow-up period was 87.0 months [IQR, 65.2–109.2] and 134 were followed over ten years. With change point analysis, both longitudinal increase of CD4 count and %CD4 increased linearly until 78.6 and 62.2 months, respectively. Stratified by baseline CD4 count (350 cells/mm3), CD4 count increased linearly until 76.2, 62.4, and 58.6 months, respectively. Moreover, the percentage of patient who achieved 500 cells/mm3 during study period was 63.5%, 87.2%, and 92.0%, respectively. Conclusion With change point analysis, restoration of CD4 count and %CD4 continued increasing linearly until 6.5 and 5 years of cART, respectively. Patients with lower baseline CD4 count showed longer CD4 count recovery than those with higher baseline CD4; however, their CD4 count did not recover as high as those with higher baseline CD4 count. Disclosures All authors: No reported disclosures.