ABSTRACT
Background: Long-acting cabotegravir (CAB-LA) is highly effective as HIV PrEP and superior to daily oral F/TDF in sexually active adults. We report a 28-yearold gender diverse patient assigned male at birth who acquired HIV-1 91 days after transitioning from F/TAF to CAB-LA despite on-time dosing. Method(s): Electronic medical records were reviewed to assess patient history and CAB-LA administration details. Plasma 4th generation HIV-1/2 Ag/Ab combination immunoassay and HIV-1 RNA quantitative PCR were performed at each injection visit. Result(s): Patient was on daily F/TAF for ten months prior to CAB-LA with acceptable adherence, missing 1 dose per week. Their medical history included hypothyroidism on levothyroxine and unconfirmed hypogonadism with illicit use of IM testosterone cypionate complicated by significantly elevated total testosterone levels. They were sexually active with cisgender men, endorsing condomless oral and anal sex with one primary partner and 20-30 unique partners per month. In the past 6 months, patient was diagnosed with syphilis and mpox. Patient was given 600mg of CAB-LA into their left gluteal medius on Day 0, 27, and 91. Day 0 and 27, plasma HIV 1/2 Ag/Ab was non-reactive and HIV-1 RNA PCR was not detected. Patient reported flu-like illness on Day 76 with positive SARS-COV-2 PCR;they completed a five-day course of nirmatrelvirritonavir with rapid resolution of symptoms. At the third injection of 600mg CAB-LA on Day 91, their plasma HIV 1/2 Ag/Ab was non-reactive but the HIV-1 RNA PCR test was detected at 1.48log c/mL. On repeat testing on Day 100, plasma HIV 1/2 Ag/Ab was reactive with HIV-1 Ab detected on differentiation assay and HIV-1 RNA PCR was detected at 1.30 log c/mL. Patient's primary partner was living with HIV resistant to NRTIs (65R, 118I) and INSTIs (92G) with undetectable plasma HIV-1 RNA for the past 24 months. Patient's viremia was below the threshold to perform standard HIV-1 sequencing;HIV-1 DNA qualitative PCR and HIV-1 proviral DNA resistance testing are currently pending. Patient ultimately started on F/TAF/DRV/COBI and DTG on Day 112. Conclusion(s): This patient's history suggests HIV-1 infection despite on-time and appropriate CAB-LA injections. To our knowledge, this is the first case of CAB-LA PrEP failure outside the setting of a clinical trial and highlights the diagnostic and management challenges that may arise with such breakthrough infections in the real world.
ABSTRACT
The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.Copyright © 2021, IAS-USA. All rights reserved.
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Background: Interaction between HIV and SARS-CoV-2 infection has not yet been fully characterized. To this purpose, an in-vitro HIV/SARS-CoV-2 coinfection assay was set up. Furthermore, the results obtained in the in-vitro model were verified in a cohort of HIV/SARS-CoV-2 coinfected young individuals. Methods: We designed an in-vitro SARS-CoV-2/HIV coinfection. We challenged PBMCs derived from 10 healthy volunteers with 1 ng/1×106 cells of HIV-1BaL and subsequently co-cultured them with a human lung epithelial cell line (CaLu3) infected with SARS-CoV-2 at 0.015 MOI. At 96 hours post HIV-1 infection, both PBMCs and CaLu3 cells were harvested for mRNA expression and proteomic analysis. Furthermore, we enrolled 85 ART-treated HIV-vertically transmitted patients (mean age 22.4 years) followed at the Unit of Pediatric Infectious Diseases, Sacco Hospital in Milan, Italy. Real-time PCR was performed to detect SARS-CoV-2 and plasma samples were tested for anti-SARS-CoV-2-specific IgG (Euroimmun Kit). The subjects who contracted SARS-CoV-2 infection (H+/S+) were compared to the HIV-positive, SARS-CoV-2 negative ones (H+/S-) and to a cohort of SARS-CoV-2 positive, HIV-negative age-matched patients (H-/S+, mean age 22.8 years). We evaluated mRNA expression of factors involved in the anti-viral immune response on PBMCs upon stimulation with SARS-CoV-2 antigens (Quantigene Plex assay) and secreted cytokines/chemokines on plasma (Multiplex Cytokine Array). Results: We observed a significant reduction of SARS-CoV-2 replication on CaLu3 cells when exposed to HIV-pre-infected PBMCs in-vitro. IL-10 expression and production were significantly higher in the coinfected condition, in both CaLu3 cells and PBMCs. The upregulation of IL-10 was associated to higher expression levels of STAT3. In the HIV-vertically transmitted cohort, 4 out of 85 subjects contracted SARS-CoV-2 infection (H+/S+). All H+/S+ patients were asymptomatic. Similarly to the data obtained in-vitro, a significant increase in both expression and production of IL-10 emerged in comparison to H+/S-and H-/S+. Conclusion: In-vitro, a dampening in SARS-CoV-2 replication, along with a higher IL-10 mRNA expression and production, have been observed in the HIV/SARS-CoV-2 coinfected condition. Presumably, IL-10 exerted its activity through the STAT3 pathway. These results were confirmed in HIV/SARS-CoV-2 coinfected subjects in which an upregulation of IL-10 was observed. Our data might be useful defining HIV/SARS-CoV-2 coinfected young individuals pathogenesis.
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Background: Lenacapavir (LEN), a potent first-in-class inhibitor of HIV-1 capsid function, is in development for treatment and prevention of HIV-1 infection. CAPELLA is an ongoing, Phase II/III study in heavily treatment-experienced (HTE) people with HIV-1 (PWH) with multidrug-resistance and ongoing viremia (≥ 400 copies/mL) evaluating LEN in combination with an optimized background regimen (OBR). Methods: In the randomized cohort (Cohort 1), participants were assigned (2:1) to add oral LEN or placebo to their failing regimen (600 mg on Day 1[D] and 2 and 300 mg on D8). At D15, those on oral LEN received subcutaneous (SC) LEN 927 mg every 6 months;those on placebo started the 2-week oral lead-in, followed by SC Q6M. All randomized participants initiated an investigator-selected, OBR at D15. In the non-randomized cohort (Cohort 2), participants started OBR concurrent with LEN (oral lead-in → SC). We report the secondary endpoint of W52 efficacy by FDA-snapshot algorithm in the randomized cohort and additional available efficacy and safety from both cohorts. Results: 72 participants were enrolled: 36 in each cohort. Overall, 25% were female, 38% Black, median age 52 years, 19% had VL > 100k c/mL, 64% had CD4 <200 cells/μ L, 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, InSTI), and 17% did not have any fully active agents in the OBR. In Cohorts 1 and 2 at W26, 81% (29/36) and 81% (29/36) achieved VL<50 c/mL. At W52, in Cohort 1, 83% (30/36) had VL< 50 c/mL;most in Cohort 2 have not reached W52 yet. At W52, CD4 count increased by a median 83 cells/μ L (Q1 to Q3: 21 to 142, n=41). Eight participants had emergent LEN resistance (4 in Cohort 1 and 4 in Cohort 2);other than 1 who died at W11 (previously reported), all 7 either had evidence of poor adherence to the OBR (n=4) or did not have any fully active agents in the OBR (n=3).No participant experienced a study drug-related serious adverse event. One participant discontinued LEN at W52 due to an AE of Grade 1 injection site nodule. LEN-related injection site reactions (ISRs) occurred in 63% (45/72) and were mostly mild or moderate (43/45). The most common non-ISR AEs were nausea and diarrhea (13% each) and COVID-19 (11%). Conclusion: Subcutaneous LEN in combination with OBR led to high rates of virologic suppression and immunologic recovery in HTE PWH at one year and was well tolerated. These results support the ongoing evaluation of LEN for treatment of multi-drug resistant HIV-1 infection.
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Background: Ending the HIV Epidemic by 2030 initiative includes phylogenetics as a molecular framework to track patterns of HIV spread. In this study, phylogenetics was combined with available epidemiological data to elucidate track evolving trends in HIV-1 spread among Men having Sex with Men (MSM) and Heterosexual (HET) populations in Quebec. Methods: Phylogenetic linkage analysis was performed using MEGA-10 and HIV-TRACE/Microbe-TRACE methodologies. New infections genotyped between 2014-2020 were stratified into groups: i) Subtype B MSM (subtype B male singletons/male-male clusters, n=1812);ii) Subtype B Heterosexual (female singletons/female-male clusters, n=432), including migrants from the Caribbean and Americas;and iii) Non-B subtype (n=737) epidemics. Test requisition data and clinical data from Clinique Actuel (n=141 and 50, 2016-2018) monitored epidemiological features in a subset of newly diagnosed persons. Results: Among MSM, annual new infections declined by 20% and 40% over the 2015-2017 and 2018-2020 periods, respectively. Overall, 45% of new infections in MSM were associated with 20 active large clusters, adding 8-96 infections/clusters from 2014-2020. Clinical data showed 37% newly diagnosed MSM were born outside Canada, 28% of whom were linked to large cluster outbreaks. Among heterosexuals with subtype B infections, there was a 31% increase from 2015-2017 followed by a 36% decline from 2018-2020 post-COVID. Of note, large cluster HET outbreaks occurred in Quebec City, Richelieu, and Northern Quebec Overall, non-B subtype infections remained steady (median 100 annually) over the 2014 to 2020 period. Several non-B subtype clusters reflect the domestic introduction and spread of subtype CRF02- AG variants. Cluster membership and cluster size was associated with recent stage infection, viral sequence recency (based on % mixed base calls) and younger age of members within individual clusters. Conclusion: Annual numbers of new HIV-1 infections have steadily declined among MSM post-2008, concomitant to improved HIV prevention paradigms. Epidemic control among MSM and HET groups has been thwarted by large cluster outbreaks. Recent arrivals to Quebec accounted for a growing number of subtype B and non-B subtype infections. HIV prevention efforts must continue in the post-COVID era, tailored to avert transmission cascades in younger persons and recent migrant populations.
ABSTRACT
Background: A novel Coronavirus first emerging in Wuhan, China, was named severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 is known as Coronavirus disease 2019 (COVID-19). HIV-1 infected individuals may be at risk of COVID-19. Objectives: This cross-sectional study evaluated the SARS-CoV-2 infection rate and COVID-19 prevalence among Iranian HIV-1-infected people. Methods: The study was conducted on 155 HIV-1-infected patients from June 2020 to October 2020. COVID-19 Ab (IgG) was detected using an enzyme immunoassay in serum specimens. Furthermore, nasopharyngeal and oropharyngeal specimens were collected. Then, the genomic RNA of SARS-CoV-2 was detected using a real-time polymerase chain reaction (RT-PCR). Clinical symptoms of the studied participants with and without COVID-19 were examined. Results: Of 155 HIV-1-infected individuals, 12 (7.7%) had positive real-time PCR results for SARS-CoV-2. Out of 12 (7.7%) patients with COVID-19, four (33.3%) were males. Anti-COVID Ab (IgG) was detected in 10 (6.5%) participants, of whom eight (80.0%) were males. The most common COVID-19 clinical symptoms, including dry cough, fever, runny nose, anosmia, and hypogeusia, were observed in seven (58.3%), five (41.7%), five (41.7%), five (41.7%), and five (41.7%) patients with COVID-19, respectively. Conclusions: A recent study has shown that the risk of SARS-CoV-2 infection in HIV-infected individuals is similar to that in the general population.