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In this review, we examine the intersection of the HIV and COVID-19 epidemics with focus on COVID-19-related health outcomes and risk factors for SARS-CoV-2 among people living with HIV (PLWH).Evidence to date do not suggest a higher incidence of SARS-CoV-2 infection among PLWH compared to the general population, although-once exposed-PLWH are at greater risk of severe COVID-19 outcomes. Key risk factors for severe COVID-19 include non-HIV comorbidities known to be associated with severe disease, as well as HIV-specific risk factors such as low CD4 + T-cell count, unsuppressed viral load, and tuberculosis co-infection. The disproportionate impact of the SARS-CoV-2 pandemic among Black, Latinx, and Native American/Alaskan Native PLWH could worsen pre-existing disparities in health outcomes among PLWH. Data on SARS-CoV-2 vaccine protection among PLWH needs additional study, although some studies suggest decreased humoral responses among those with low CD4 + T-cell counts, while there is a signal of increased vaccine breakthrough rates among PLWH in two large observational cohorts. Data on post-acute sequelae of SARS-CoV-2 (PASC) among PLWH is also limited. PLWH do not have a higher susceptibility to SARS-CoV-2, but once exposed, they are at higher risk of severe COVID-19 outcomes. Additional resources will need to be dedicated to the development of interventions to improve health outcomes and address disparities among PLWH impacted by the COVID-19 pandemic.

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.We identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Introduction The high cost of viral load (VL) testing limits its use for antiretroviral treatment (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts PrEP breakthroughs but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at increased risk of virologic failure. Methods Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate (DP) analysed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing performed. Results Of 48 participants, 18 (37.5%) had virologic failure (VL>400 copies/mL) at the time of the study including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors (PI) and 0 of 3 receiving dolutegravir (DTG). Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in 2 out of 3 without regimen-relevant resistance; p=0.02. Conclusion In participants on EFV-based regimens returning to care, virologic failure was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.

Background After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. Methods We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. Results Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21–1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01–1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05–3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2–3.5). Conclusions The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.In a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status), and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.We observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen (EBNA) IgG levels, but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52).Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.Long-term Impact of Infection with Novel Coronavirus (LIINC); NCT04362150FUNDING. This work was supported by the National Institute of Allergy and Infectious Diseases NIH/NIAID 3R01AI141003-03S1 to TJ Henrich, R01AI158013 to M Gandhi and M Spinelli, K24AI145806 to P Hunt, and by the Zuckerberg San Francisco Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine. MJP is supported on K23 A137522 and received support from the UCSFBay Area Center for AIDS Research (P30-AI027763).

BACKGROUND Tenofovir alafenamide (TAF) is increasingly used in HIV treatment, with or without agents that require pharmacologic boosters such as ritonavir/cobicistat. Boosters increase TAF levels, so the TAF dose is lowered in single-pill combinations. We hypothesized that individuals on dose-adjusted boosted TAF would have similar urine tenofovir (TFV) concentrations to those on unboosted TAF. SETTING/METHODS We collected urine samples from patients with HIV on TAF, with evidence of virologic suppression and high self-reported adherence at 2 San Francisco clinics from June 2019 to January 2020. We measured urine TFV levels by liquid chromatography/tandem mass spectrometry and used linear regression to compare natural log-transformed urine TFV levels for patients on boosted versus unboosted TAF. RESULTS Our analysis included 30 patients on unboosted TAF (25 mg daily TAF) and 15 on boosted TAF (12 on 10 mg daily TAF and 3 on 25 mg daily TAF). Patients on unboosted vs. boosted TAF had similar baseline age, weight, sex, and creatinine. In unadjusted univariate linear regression, there were no significant differences in urine TFV levels based on presence/absence of boosting after TAF dose reduction to 10 mg (geometric mean ratio 1.07; 95% confidence interval: 0.53 to 2.16). This finding was unchanged in adjusted analysis. CONCLUSIONS No significant differences in urine TFV levels were seen for patients on unboosted vs. boosted dose-reduced TAF. These results have important implications for our forthcoming point-of-care urine immunoassay for TAF, implying that separate adherence cutoffs will not be necessary for patients on boosters and dose-reduced TAF. A single POC TAF immunoassay will, thus, support monitoring on most TAF-based antiretroviral therapy.

We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination, people living with human immunodeficiency virus (HIV, PLWH) had lower surrogate virus neutralization test response (P = .03) and a trend toward lower immunoglobulin G (IgG) response (P = .08), particularly among those with lower CD4+ T-cell counts and who received the BNT162b2 vaccine. Study of the impact of supplemental vaccine doses among PLWH is needed.

Summary Background Most cohorts show similar or lower COVID-19 incidence among people living with HIV compared with the general population. However, incidence might be affected by lower testing rates among vulnerable populations. We aimed to compare SARS-CoV-2 IgG seroprevalence, disease severity, and neutralising antibody activity after infection among people with and without HIV receiving care in a county hospital system over a 3-month period. Methods In this matched case-control observational study, remnant serum samples were collected between Aug 1 and Oct 31, 2020, from all people living with HIV who underwent routine outpatient laboratory testing in a municipal health-care system (San Francisco General Hospital, CA, USA). Samples from people living with HIV were date of collection-matched (same day) and age-matched (±5 years) to samples from randomly selected adults (aged 18 years or older) without HIV receiving care for chronic conditions at the same hospital. We compared seroprevalence by HIV status via mixed-effects logistic regression models, accounting for the matched structure of the data (random effects for the matched group), adjusting for age, sex, race or ethnicity, and clinical factors (ie, history of cardiovascular or pulmonary disease, and type 2 diabetes). Severe COVID-19 was assessed in participants with past SARS-CoV-2 (IgG or PCR) infection by chart review and compared with multivariable mixed-effects logistic regression, adjusting for age and sex. SARS-CoV-2 IgG, neutralising antibody titres, and antibody avidity were measured in serum of participants with previous positive PCR tests and compared with multivariable mixed-effects models, adjusting for age, sex, and time since PCR-confirmed SARS-CoV-2 infection. Findings 1138 samples from 955 people living with HIV and 1118 samples from 1062 people without HIV were tested. SARS-CoV-2 IgG seroprevalence was 3·7% (95% CI 2·4 to 5·0) among people with HIV compared with 7·4% (5·7 to 9·2) among people without HIV (adjusted odds ratio 0·50, 95% CI 0·30 to 0·83). Among 31 people with HIV and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5·52 (95% CI 1·01 to 64·48) times higher among people living with HIV. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations were lower (percentage change −53%, 95% CI −4 to −76), pseudovirus neutralising antibody titres were lower (−67%, −25 to −86), and avidity was similar (7%, −73 to 87) among people living with HIV compared with those without HIV. Interpretation Although fewer infections were detected by SARS-CoV-2 IgG testing among people living with HIV than among those without HIV, people with HIV had more cases of severe COVID-19. Among people living with HIV with past SARS-CoV-2 infection, lower IgG concentrations and pseudovirus neutralising antibody titres might reflect a diminished serological response to infection, and the similar avidity could be driven by similar time since infection. Funding US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

Background Therapeutic drug monitoring measures antiretroviral adherence more accurately than self-report but has not been available at the point-of-care (POC) until now. We compare a novel POC test for urine tenofovir to laboratory-based enzyme-linked immunosorbent assay (ELISA) testing in diverse patient populations urine pre-exposure prophylaxis (PrEP). Setting Urine samples were analyzed using ELISA and the POC lateral flow immunoassay (LFA) test from 2 cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited Kenyan and Ugandan heterosexual men and women, and the IBrEATHe Study, which recruited US transgender women and men using gender-affirming hormone therapy. Methods We calculated the sensitivity, specificity, and accuracy of the POC test compared with ELISA at a cutoff of 1500 ng/mL. Results Overall, 684 urine samples were tested from 324 participants in the 2 cohorts. In Partners PrEP, 454 samples from 278 participants (41% women) were tested with a median age of 33 years. In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested with a median age of 31 years. Comparison of the LFA read-out to ELISA yielded 100% sensitivity [97.5% one-sided confidence interval (CI) = 99.3%], 98.3% specificity (95% CI = 95.2% to 99.7%), and 99.6% accuracy (95% CI = 98.7% to 99.9%). Conclusion The sensitivity, specificity, and accuracy of a novel POC test for urine tenofovir all exceeded 98% when compared with a laboratory-based ELISA method when tested in diverse patient populations. Given the LFA's high accuracy and expected low cost, this POC test is a promising tool to support antiretroviral adherence that could be widely scalable to real-world clinical settings.

PURPOSE OF REVIEW: Traditional methods to assess antiretroviral adherence, such as self-report, pill counts, and pharmacy refill data, may be inaccurate in determining actual pill-taking to both antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP). HIV viral loads serve as surrogates of adherence on ART, but loss of virologic control may occur well after decreases in adherence and viral loads are not relevant to PrEP RECENT FINDINGS: Pharmacologic measures of adherence, electronic adherence monitors, and ingestible electronic pills all serve as more objective metrics of adherence, surpassing self-report in predicting outcomes. Pharmacologic metrics can identify either recent adherence or cumulative adherence. Recent dosing measures include antiretroviral levels in plasma or urine, as well as emtricitabine-triphosphate in dried blood spots (DBS) for those on tenofovir-emtricitabine-based therapy, A urine tenofovir test has recently been developed into a point-of-care test for bedside adherence monitoring. Cumulative adherence metrics assess adherence over weeks to months and include measurement of tenofovir-diphosphate in peripheral blood mononuclear cells or DBS, as well as ART levels in hair. Electronic adherence monitors and ingestible electronic pills can track pill bottle openings or medication ingestion, respectively. SUMMARY: New and objective approaches in adherence monitoring can be used to detect nonadherence prior to loss of prevention efficacy or virologic control with PrEP or ART, respectively.

OBJECTIVE: HIV prevention and treatment studies demonstrate that pharmacologic adherence metrics are more accurate than self-report. Currently-available metrics use liquid-chromatography/tandem-mass-spectrometry (LC-MS/MS), which is expensive and laboratory-based. We developed a specific and sensitive antibody against tenofovir, the backbone of treatment and prevention, but conversion to a lateral flow assay (LFA) –analogous to a urine pregnancy test- is required for point-of-care testing. We describe the development of the first LFA to measure antiretroviral adherence in real-time. METHODS: Previous work in a directly-observed therapy study of providing tenofovir-disoproxil fumarate (TDF) to HIV-noninfected volunteers at various simulated adherence patterns defined the appropriate cut-off for the LFA (1500ng tenofovir/ml urine). We developed the LFA using a sample pad for urine; a conjugate pad coated with TFV-specific antibodies conjugated to colloidal gold nanoparticles; a nitrocellulose membrane striped with tenofovir-antigen (test line) and a control line; with an absorbent pad to draw urine across the reaction membrane. RESULTS: We tested 300 urine samples collected from the directly-observed therapy study by this LFA and the gold-standard method of LC-MS/MS. The LFA demonstrated 97% specificity (95% CI: 93% to 99%) and 99% sensitivity (94% to 100%) compared to LC-MS/MS. The LFA accurately classified 98% of patients who took a dose within 24 hours as adherent. CONCLUSION: We describe the development and validation of the first point-of-care assay to measure short-term adherence to HIV prevention and treatment in routine settings. The assay is low-cost, easy-to-perform and measures the breakdown product (tenofovir) of both TDF and tenofovir alafenamide (TAF). This assay has the potential to improve HIV and PrEP outcomes worldwide by triggering differentiated service delivery with further study merited.

BackgroundLimited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).MethodsWe measured SARS-CoV-2 specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n=39 and n=43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC.ResultsAmong PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2 specific memory CD8+ T cells (p=0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2 specific CD4+ T cells (p=0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2 specific CD8+ T cells (0.34-fold effect, p=0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p=0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.ConclusionsWe identified potentially important differences in SARS-CoV-2 specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Background There is mounting evidence for the presence of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life. Methods We assembled a cohort of adults with a documented history of SARS-CoV-2 RNA positivity at ≥2 weeks past onset of coronavirus disease 2019 (COVID-19) symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life. Results Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 were symptomatic but not hospitalized, and 44 were symptomatic and hospitalized. During the postacute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping, and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared with pre-COVID-19. Two clusters of symptom domains were identified. Conclusions Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple subphenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various subgroups of PASC.

To assess SARS-CoV-2 outcomes, we matched a municipal COVID-19 registry and clinic rosters from a municipal primary care network containing a large HIV clinic and assessed clinical outcomes by HIV status. The risk of severe COVID-19 was higher among people living with HIV (PLWH; adjusted relative risk=1.84, 95% confidence interval=1.05–3.25), while SARS-CoV-2 incidence was lower despite higher testing rates. SARS-CoV-2 vaccination campaigns should prioritize PLWH to prevent severe COVID-19 disease given potentially higher risk.

Objectives Inaccuracies in cause-of-death information in death certificates can reduce the validity of national death statistics and result in poor targeting of resources to reduce morbidity and mortality in people with HIV. Our objective was to measure the sensitivity, specificity, and agreement between multiple causes of deaths from death certificates obtained from the National Death Index (NDI) and causes determined by expert physician review. Methods Physician specialists determined the cause of death using information collected from the medical records of 50 randomly selected HIV-infected people who died in San Francisco from July 1, 2016, through May 31, 2017. Using expert review as the gold standard, we measured sensitivity, specificity, and agreement. Results The NDI had a sensitivity of 53.9% and a specificity of 66.7% for HIV deaths. The NDI had a moderate sensitivity for non–AIDS-related infectious diseases and non–AIDS-related cancers (70.6% and 75.0%, respectively) and high specificity for these causes (100.0% and 94.7%, respectively). The NDI had low sensitivity and high specificity for substance abuse (27.3% and 100.0%, respectively), heart disease (58.3% and 86.8%, respectively), hepatitis B/C (33.3% and 97.7%, respectively), and mental illness (50.0% and 97.8%, respectively). The measure of agreement between expert review and the NDI was lowest for HIV (κ = 0.20); moderate for heart disease (κ = 0.45) and hepatitis B/C (κ = 0.40); high for non–AIDS-related infectious diseases (κ = 0.76) and non–AIDS-related cancers (κ = 0.72); and low for all other causes of death (κ < 0.35). Conclusions Our findings support education and training of health care providers to improve the accuracy of cause-of-death information on death certificates.

Objective:Dissemination of pre-Exposure Prophylaxis (PrEP) is a priority for reducing new HIV infections, especially among vulnerable populations. However, there are limited data available on PrEP discontinuation following initiation, an important component of the PrEP cascade.Design:Patients receiv

BACKGROUND: Current pharmacologic adherence monitoring for antiretrovirals involves expensive, labor-intensive liquid-chromatography/tandem-mass-spectrometry (LC-MS/MS)-based methods. Antibody-based assays can monitor and support adherence in real-time. We developed a tenofovir (TFV)-based immunoassay and further validated it in a directly-observed-therapy (DOT) study. DESIGN: Pharmacologic DOT study of TFV disoproxil fumarate (TDF)/emtricitabine (FTC) administered to HIV-noninfected volunteers METHODS: The TARGET study provided directly-observed TDF 300mg/FTC 200mg 7 (high adherence), 4 (moderate) and 2 doses/week (low) to 30 volunteers (10/group) in Thailand, collecting a total of 637 urine samples over 6-weeks of administration and during wash-out. ELISA measured urine TFV levels by the immunoassay and LC-MS/MS-based concentrations served as the gold-standard. A mixed-effects regression model evaluated cut-offs for a point-of-care (POC) assay. Performance characteristics of the immunoassay were compared to LC-MS/MS at a chosen cut-off. RESULTS: Median TFV levels were 12,000ng/mL by the immunoassay 1-day after dosing; 5000ng/mL 2-days after dosing; 1500ng/mL 3-days after dosing and below the lower-limit-of-quantification (LLOQ) thereafter (≥4 days). An immunoassay cut-off of 1500ng/mL accurately classified 98% of patients who took a dose 24 hours ago as adherent. The specificity and sensitivity of the immunoassay compared to LC-MS/MS at the 1500ng/mL cut-off were 99% and 94%; the correlation between TFV levels by the two assays was high (0.92, p

OBJECTIVE We examined the relationship between urine tenofovir (TFV) levels measured with a novel immunoassay, which permits point-of-care testing, with HIV seroconversion and objective adherence metrics in a large preexposure prophylaxis (PrEP) demonstration project. DESIGN Secondary analysis of stored specimens from an open-label PrEP cohort study. METHODS We examined the association between undetectable urine TFV levels and HIV seroconversion in iPrEx open-label extension using generalized estimating equations. We examined rank correlations between levels of TFV and emtricitabine in urine, dried blood spots (DBS), and hair and determined the sensitivity and specificity of undetectable urine TFV for predicting dosing cut-offs in DBS. RESULTS The median urinary TFV level was 15 000 ng/ml in those who remained HIV-negative (n = 105; interquartile range: 1000-45 000); 5500 in those who eventually seroconverted (n = 11; interquartile range: 1000-12 500); and all were undetectable at seroconversion (n = 9; P

Integrase inhibitor–based (INSTI) antiretroviral therapy (ART) regimens are preferred for most people with HIV (PWH). We examined factors associated with INSTI use among PWH in San Francisco who started ART in 2009–2016. PWH who experienced homelessness were less likely, and older PWH were more likely, to use an INSTI.

BACKGROUNDAs the coronavirus disease 2019 (COVID-19) pandemic continues and millions remain vulnerable to infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), attention has turned to characterizing post-acute sequelae of SARS-CoV-2 infection (PASC).METHODSFrom April 21 to December 31, 2020, we assembled a cohort of consecutive volunteers who a) had documented history of SARS-CoV-2 RNA-positivity; b) were ≥ 2 weeks past onset of COVID-19 symptoms or, if asymptomatic, first test for SARS-CoV-2; and c) were able to travel to our site in San Francisco. Participants learned about the study by being identified on medical center-based registries and being notified or by responding to advertisements. At 4-month intervals, we asked participants about physical symptoms that were new or worse compared to the period prior to COVID-19, mental health symptoms and quality of life. We described 4 time periods: 1) acute illness (0-3 weeks), 2) early recovery (3-10 weeks), 3) late recovery 1 (12-20 weeks), and 4) late recovery 2 (28-36 weeks). Blood and oral specimens were collected at each visit.RESULTSWe have, to date, enrolled 179 adults. During acute SARS-CoV-2 infection, 10 had been asymptomatic, 125 symptomatic but not hospitalized, and 44 symptomatic and hospitalized. In the acute phase, the most common symptoms were fatigue, fever, myalgia, cough and anosmia/dysgeusia. During the post-acute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping and anosmia/dysgeusia were the most commonly reported symptoms, but a variety of others were endorsed by at least some participants. Some experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with ambulation and performance of usual activities. The median visual analogue scale value rating of general health was lower at 4 and 8 months (80, interquartile range [IQR]: 70-90; and 80, IQR 75-90) compared to prior to COVID-19 (85; IQR 75-90). Biospecimens were collected at nearly 600 participant-visits.CONCLUSIONAmong a cohort of participants enrolled in the post-acute phase of SARS-CoV-2 infection, we found many with persistent physical symptoms through 8 months following onset of COVID-19 with an impact on self-rated overall health. The presence of participants with and without symptoms and ample biological specimens will facilitate study of PASC pathogenesis. Similar evaluations in a population-representative sample will be needed to estimate the population-level prevalence of PASC.

We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.

Antibody detection of prior SARS-CoV-2 infection depends on severity, assay, and timing with implications for serosurveillance., Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

A detailed understanding of long-term SARS-CoV-2-specific T cell responses and their relationship to humoral immunity and markers of inflammation in diverse groups of individuals representing the spectrum of COVID-19 illness and recovery is urgently needed. Data are also lacking as to whether and how adaptive immune and inflammatory responses differ in individuals that experience persistent symptomatic sequelae months following acute infection compared to those with complete, rapid recovery. We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally up to 9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection. The participants had varying degrees of initial disease severity and were enrolled in the northern California Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort. Adaptive T cell responses remained remarkably stable in all participants across disease severity during the entire study interval. Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated with higher long-term SARS-CoV2-specific CD8+ T cell responses, independent of initial disease severity or age. Neutralizing antibody levels were strongly correlated with SARS-CoV-2-specific CD4+ T but not CD8+ T cell responses. Importantly, we did not identify substantial differences in long-term virus-specific T cell or antibody responses between participants with and without COVID-19-related symptoms that persist months after initial infection.

From directly observed therapy studies, urine tenofovir (TFV) levels were 74% lower when taking tenofovir alafenamide (TAF) vs tenofovir disoproxil fumarate. Urine TFV remains quantifiable across a range of TAF adherence patterns, but a separate point-of-care lateral flow immunoassay with a lower TFV threshold will be needed to support TAF adherence monitoring.

Adherence to non-pharmaceutical interventions to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been highly variable across settings, particularly in the USA. In this Personal View, we review data supporting the importance of the viral inoculum (the dose of viral particles from an infected source over time) in increasing the probability of infection in respiratory, gastrointestinal, and sexually transmitted viral infections in humans. We also review the available evidence linking the relationship of the viral inoculum to disease severity. Non-pharmaceutical interventions might reduce the susceptibility to SARS-CoV-2 infection by reducing the viral inoculum when there is exposure to an infectious source. Data from physical sciences research suggest that masks protect the wearer by filtering virus from external sources, and others by reducing expulsion of virus by the wearer. Social distancing, handwashing, and improved ventilation also reduce the exposure amount of viral particles from an infectious source. Maintaining and increasing non-pharmaceutical interventions can help to quell SARS-CoV-2 as we enter the second year of the pandemic. Finally, we argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed.

Background: Most cohorts show similar or lower COVID-19 incidence among people living with HIV (PLWH) compared to the general population. However, incidence may be impacted by lower testing rates among vulnerable populations. We compared SARS-CoV-2 IgG seroprevalence, disease severity, and neutralizing antibody activity after infection among people with and without HIV receiving care within a county hospital system over a three-month period. Methods: From August through October 2020, remnant serum samples were collected from all PLWH who underwent routine outpatient laboratory testing in a municipal healthcare system which houses a large HIV clinic. Patients with HIV were date-of-collection and age-matched (same day, +/- 5 years respectively) to adults without HIV. SARS-CoV-2 IgG and neutralizing antibody titers were measured in serum. Severe disease was assessed by chart review. Findings: Overall, 2,256 samples from 955 PLWH and 1062 people without HIV were tested. Among PLWH, the seroprevalence was 3.7% as compared to 7.4% among people without HIV (adjusted odds ratio (AOR) 0·48; 95% Confidence Interval (CI): 0·34; 0·71). Among those with evidence of prior infection (IgG or PCR), the odds of severe disease were more than 5-fold higher among PLWH (OR 5·13 95% CI: 1·05; 38·9). Among those with past infection, SARS-CoV-2 IgG levels were 45% lower among PLWH vs. those without HIV (95% CI: 22%; 61%); neutralizing antibody titers were 63% lower among PLWH (2%-78%). Interpretation: Among PLWH, there were approximately 50% lower odds of past SARS-CoV-2 infection, possibly due to greater non-pharmaceutical intervention adherence among a population with experience of the HIV epidemic. However, in spite of fewer infections, PLWH experienced more cases of severe disease. Among PLWH with past SARS-CoV-2 infection, lower neutralizing antibody titers were observed and may lead to increased risk of severe COVID-19 disease or reinfection. PLWH should be followed after vaccination to ensure they mount and maintain sufficient responses. Funding Statement: This work was funded by NIH/NIAID R01AI158013. Declaration of Interests: MAS, DVG, TJH, MG, and LBB report funding from the NIH during conduct of the study. DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors have nothing to declare. Ethics Approval Statement: As only remnant samples were used, the University of California, San Francisco IRB did not require informed consent for study participation.The UCSF IRB # is 20-30387.

Background: Limited data is available on whether there are differences in the humoral response to mRNA SARS-CoV-2 vaccination by HIV status. We compared surrogate virus neutralization tests (sVNT) and anti-receptor-binding-domain (RBD) IgG concentrations by HIV status, as well as if responses differed by mRNA vaccine type. Methods: Remnant serum samples were collected during the month of May 2021 from all people living with HIV (PLWH) undergoing outpatient laboratory testing in a U.S. municipal health-care system. Samples from 100 PLWH were then matched on the same number of days following second mRNA vaccination, age (+/- 5 years), birth sex, and type of mRNA vaccine to samples from 100 adults receiving care for chronic conditions at the same hospital. Antibody responses were measured using a previously validated sVNT and anti-RBD IgG, with non-response defined as the limit of detection at 200 copies/mL was associated with 89% lower titers (GMR 0.11; 95% CI=0.01-0.84). Interpretation: PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, particularly among those with low CD4+ T-cell counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Funding: This research was supported by U.S. National Institute of Allergy and Infectious Diseases (NIAID) R01AI158013 (M.A.S. and M.G.), and U.S. NIAID P30AI027763 (M.G.) Declaration of Interest: DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors declare no competing interests. Ethical Approval: As only remnant samples were used, the University of California, San Francisco IRB did not require informed consent for study participation. The UCSF IRB # is 20-30387.

Introduction The COVID-19 pandemic has required a shift of many routine primary care visits to telemedicine, potentially widening disparities in care access among vulnerable populations. In a publicly-funded HIV clinic, we aimed to evaluate a pre-visit phone-based planning intervention to address anticipated barriers to telemedicine. Methods We conducted a pragmatic randomized controlled trial of patients scheduled for a phone-based HIV primary care visit at the Ward 86 HIV clinic in San Francisco from 15 April to 15 May 2020. Once reached by phone, patients were randomized to either have a structured pre-visit planning intervention to address barriers to an upcoming telemedicine visit versus a standard reminder call. The primary outcome was telemedicine visit attendance. Results Of 476 scheduled telemedicine visits, 280 patients were reached by a pre-visit call to offer enrollment. Patients were less likely to be reached if virally unsuppressed (odds ratio (OR) 0.11, 95% confidence intervals (CI) 0.03–0.48), CD4 Conclusions A structured phone-based planning call to address barriers to telemedicine in a public HIV clinic was less likely to reach patients with poorly-controlled HIV and patients experiencing homelessness, suggesting additional interventions may be needed in this population to ensure access to telemedicine-based care. Among patients reachable by phone, telemedicine visit attendance was high and not improved with a structured pre-visit intervention, suggesting that standard reminders may be adequate in this population.

Purpose of review We examine the interplay between the HIV and COVID-19 epidemics, including the impact of HIV on COVID-19 susceptibility and severe disease, the effect of the COVID-19 epidemic on HIV prevention and treatment, and the influence of the HIV epidemic on responses to COVID-19. Recent findings Evidence to date does not suggest that people living with HIV (PLWH) have a markedly higher susceptibility to SARS-CoV-2 infection, with disparities in the social determinants of health and comorbidities likely having a greater influence. The majority of literature has not supported a higher risk for severe disease among PLWH in Europe and the United States, although a large, population-based study in South Africa reported a higher rate of death due to COVID-19. Higher rates of comorbidities associated with COVID-19 disease severity among PLWH is an urgent concern. COVID-19 is leading to decreased access to HIV prevention services and HIV testing, and worsening HIV treatment access and virologic suppression, which could lead to worsening HIV epidemic control. Conclusion COVID-19 is threatening gains against the HIV epidemic, including the U.S. Ending the HIV Epidemic goals. The ongoing collision of these two global pandemics will continue to need both study and interventions to mitigate the effects of COVID-19 on HIV efforts worldwide.

The COVID-19 pandemic is expected to hinder US End the HIV Epidemic goals. We evaluated viral suppression and retention-in-care before and after telemedicine was instituted, in response to shelter-in-place mandates, in a large, urban HIV clinic. The odds of viral nonsuppression were 31% higher postshelter-in-place (95% confidence interval = 1.08-1.53) in spite of stable retention-in-care and visit volume, with disproportionate impact on homeless individuals. Measures to counteract the effect of COVID-19 on HIV outcomes are urgently needed.

PrEP persistence, or PrEP use over time, has been shown to be short, with most PrEP users stopping within 6–12 months. Furthermore, those most vulnerable to HIV often use PrEP for shorter periods. This qualitative study explores patient, provider, and contextual factors that influence PrEP persistence. In interviews with 25 PrEP users and 18 PrEP providers in San Francisco’s safety net clinics, we analyze the perceived benefits and difficulties of taking PrEP, including structural barriers. We identify different steps in receipt of PrEP care (clinic visits and lab tests, pharmacy interactions, and medication adherence), and describe barriers and facilitators for providers and patients at each step. Our findings suggest that drop-in visits, streamlined testing, standing orders for labs, and 90-day PrEP prescriptions are highly desirable for many PrEP users. Also important are the proactive provision of adherence support and counseling, and referrals for housing, substance use, and mental health services.

Pre-exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in-depth interviews with people who HIV seroconverted after using PrEP.We identified individuals who initiated PrEP in an integrated safety-net public health system and performed in-depth chart review to determine person-time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention's Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in-depth interviews with those who seroconverted.Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person-years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5-fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on-demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP's benefit versus self-perceived risk; and entering a primary partnership. The individual who developed HIV using on-demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing.HIV incidence during gaps in PrEP use was nearly eight-fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non-daily PrEP may require additional education and support in the United States.

Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.

Background The worldwide expansion of preexposure prophylaxis (PrEP) with oral tenofovir-disoproxil-fumarate/emtricitabine will be critical to ending the HIV epidemic. However, maintaining daily adherence to PrEP can be difficult, and the accuracy of self-reported adherence is often limited by social desirability bias. Pharmacologic adherence monitoring (measuring drug levels in a biomatrix) has been critical to interpreting PrEP trials, but testing usually requires expensive equipment and skilled personnel. We have recently developed a point-of-care (POC) immunoassay to measure tenofovir in urine, allowing real-time adherence monitoring for the first time. Objective The goal of this study is to examine a point-of-care adherence metric in PrEP to support and increase adherence via a randomized controlled trial. Methods The paper describes the protocol for a pilot randomized controlled trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine test to provide real-time adherence feedback among women on PrEP. Eligible women (n=100) will be HIV-negative, ≥18 years old, and recruited from a clinic in Kenya that provides PrEP. Participants will be randomized 1:1 to the intervention of providing real-time feedback via the assay versus standard of care adherence counseling. Acceptability by participants will be assessed by a quantitative survey, as well as by qualitative data collected via in-depth interviews (n=20) and focus group discussions (n=4 groups, 5-10 women each). Feasibility will be assessed by the proportion of women retained in the study, the mean number of missed visits, the proportion of planned urine assessments completed, and messages delivered, while in-depth interviews with providers (n=8) will explore the ease of administering the urine test. Tenofovir levels in hair will serve as long-term adherence metrics. A linear mixed-effects model will estimate the effect of the intervention versus standard of care on logarithmically transformed levels of tenofovir in hair. Results This study has been funded by the National Institute of Health, approved by the Kenya Medical Research Institute Institutional Review Board, and will commence in June 2020. Conclusions A novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale trial assessing the impact of real-time adherence monitoring/feedback on HIV prevention. Improving adherence to PrEP will have long-term implications for efforts to end the HIV epidemic worldwide. Trial Registration ClinicalTrials.gov NCT03935464; https://clinicaltrials.gov/ct2/show/NCT03935464 International Registered Report Identifier (IRRID) PRR1-10.2196/15029

Introduction Pre‐exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in‐depth interviews with people who HIV seroconverted after using PrEP. Methods We identified individuals who initiated PrEP in an integrated safety‐net public health system and performed in‐depth chart review to determine person‐time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention’s Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in‐depth interviews with those who seroconverted. Results Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person‐years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5‐fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on‐demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP’s benefit versus self‐perceived risk; and entering a primary partnership. The individual who developed HIV using on‐demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing. Conclusions HIV incidence during gaps in PrEP use was nearly eight‐fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non‐daily PrEP may require additional education and support in the United States.

Current strategies to prevent sexually transmitted infections (STIs) are not controlling the epidemic. The efficacy of doxycycline STI postexposure prophylaxis shows promise in pilot studies, but wider acceptability is unknown. A majority (84%) of diverse individuals using a gay social networking application were interested in doxycycline STI postexposure prophylaxis. Doxycycline STI postexposure prophylaxis should be examined in larger trials.

Background Limited data are available on whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type. Methods We saved residual outpatient laboratory samples of all previously mRNA-vaccinated individuals in the adult medicine clinics of a public hospital with a large outpatient HIV clinic during May 2021, and then excluded individuals with prior SARS-CoV-2 infection. We next 1:1 matched 100 PLWH to 100 outpatient HIV-negative adult medicine patients receiving care for chronic medical conditions on days since completion of second vaccination (minimum 10), sex, age +/-5 years, and the type of mRNA vaccine received. We defined a non-response as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units, and compared non-response by HIV status using mixed models. Results In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine; the median age was 59. The median time from second vaccination was 35 days (IQR: 20–63). Among PLWH, the median CD4+ T-cell count was 511 (IQR: 351–796) and 5 individuals had HIV RNA > 200. We found 2.4-fold greater odds of pseudovirus neutralizing antibody non-response among PLWH compared to people without HIV (95% CI=1.1–5.4). Although few individuals in each group did not mount an IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI=0.36–0.88). Among PLWH, when adjusting for age, sex, and days post-vaccination, each 100-cell increase in CD4+T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22; 95% CI=1.09–1.37). Unsuppressed HIV RNA >200 was associated with 89% lower neutralizing antibody titers (GMR 0.11; 95% CI=0.01–0.84). Receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23; 95% CI=0.08–0.65) among PLWH. Post-mRNA Vaccination SARS-CoV-2 IgG Concentrations and Pseudovirus Neutralizing Titers by HIV Status and Vaccine Conclusion PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, with the highest non-response among those with low CD4+ counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Immunization strategies to improve immune responses among PLWH should be studied, and may include booster vaccination or preference of the mRNA-1273 vaccine in this group. Disclosures Matthew A. Spinelli, MD, MAS, Nothing to disclose Monica Gandhi, MD, MPH, Nothing to disclose

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses., Graphical abstract, CD4+ and CD8+ T cell responses following natural infection with COVID-19 are stable over 8 months. Individuals with PASC demonstrate a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells.

Women in the general population experience more food insecurity than men. Few studies have examined food insecurity's impact on HIV treatment outcomes among women. We examined the association between food insecurity and HIV outcomes in a multi-site sample of HIV-infected women in the United States (n=1154). Two-fifths (40%) of participants reported food insecurity. In an adjusted multivariable Tobit regression model, food insecurity was associated with 2.08 times higher viral load (95% confidence interval (CI): 1.04, 4.15) and lower CD4+ counts (-42.10, CI: -81.16, -3.03). Integration of food insecurity alleviation into HIV programs may improve HIV outcomes in women.