Keri N. Althoff

Objectives: Among people with HIV with hepatitis C virus (HCV) co‐infection, we examined differences in haemoglobin A1c (HbA1c), total cholesterol (TC), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL) and atherosclerotic cardiovascular disease (ASCVD) risk score at 12‐months following direct acting antiviral (DAA) initiation, comparing people with HIV who initiated DAA with those who did not to explore the utility of DAAs beyond HCV elimination. Methods: Utilizing a nested exposure‐matched study of people with HIV age 18 years, on antiretroviral therapy from the NA‐ACCORD and the Mass General Brigham HIV cohorts between 01/1/2014 and 12/31/2022, people with HIV with HCV co‐infection were identified by detectable plasma HCV RNA. People with HIV who initiated DAA were matched 1:1 with people with HIV who did not initiate DAA. Multivariable linear regression models estimated HbA1c ( N = 2374), TC ( N = 3418) and ASCVD risk score ( N = 488) at 12‐months comparing people with HIV who initiated DAAs versus did not. Results: We identified no significant difference in the mean HbA1c at 12‐months comparing DAA initiators to DAA non‐initiators (β: 0.00%, 95% confidence interval [CI] −0.09% to 0.08%). The mean TC at 12‐months was 13 mg/dL (95% CI 11–16 mg/dL) higher in DAA initiators and largely due to increases in LDL. There was no significant difference in the mean ASCVD risk score at 12‐months when comparing DAA initiators with those who did not initiate DAAs (β: 1.10, 95% CI −0.09 to 2.20). Conclusion: People with HIV with HCV who initiated DAA demonstrated no statistically significant difference in HbA1c or ASCVD risk score at 12‐months compared to HIV/HCV co‐infected persons who did no initiate DAA. However, TC and LDL levels increased 12 months following DAA treatment.

Among people with human immunodeficiency virus (PWH), initiating antiretroviral therapy (ART) is associated with weight gain that might increase the risk of cardiometabolic outcomes. We estimated the effect of hypothetical interventions to restrict increases in body mass index (BMI) in the 2 years after ART initiation on the 7-year risk of incident type 2 diabetes mellitus (T2DM) among PWH in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) clinical cohorts using the parametric extended g-formula. Among 13 822 normal-weight or overweight PWH (BMI ≥ 18.5 and ≤ 29.9 kg/m2) who initiated ART between 2012 and 2021, the 7-year risk of T2DM was 5.6% (95% confidence interval [CI], 4.8%, 6.3%). Compared to no intervention on BMI, if BMI increase during the first 2 years was capped at 5% of baseline BMI, the risk ratio (RR) for T2DM risk was 0.94 (95% CI, 0.86, 1.03); if BMI was capped at 29.9 kg/m2, the RR was 0.88 (95% CI, 0.80, 0.97); and if PWH were prevented from gaining any weight over the first 2 years, the RR was 0.81 (95% CI, 0.72, 0.92). These results provide preliminary evidence to promote studies of real weight-maintenance interventions among PWH initiating ART.

Background: Temporary COVID-19-related restrictions disrupted routine HIV care and viral load (VL) testing for people with HIV (PWH). Whether and when encounters and VL suppression returned to prepandemic levels remains unclear. We aimed to evaluate changes in HIV clinical encounter frequency and VL suppression from 2018 through 2021, and assess the impact of COVID-19 restriction policy. Methods: Adults (≥18 years) with HIV from 12 US clinical cohorts with ≥1 VL test from June 2020 to December 2021 were categorized into mutually exclusive HIV care groups: (1) in-care before restrictions, (2) new-to-care, and (3) re-engaging during restrictions. Logistic regression with generalized estimating equations was used to estimate adjusted odds ratios (aOR) of unsuppressed VL (>200 copies/mL) for HIV care groups from June 2020 to December 2021. A linear mixed model evaluated associations between state-level COVID-19 policy strength (mild, moderate, or strong) and unsuppressed VL. Results: Among PWH in-care (n = 48 605), encounter frequency decreased sharply during early COVID-19 restrictions but returned to prepandemic levels by December 2020, and suppressed VL rate remained above 91%. New-to-care (n = 105) or re-engaging (n = 483) individuals did not increase odds of unsuppressed VL (vs in-care, aOR = 0.91 [95% CI: 0.73, 1.13]). Those living in states with strong (vs mild, aOR = 1.31 [0.93, 1.86]) COVID-19 restriction policies had increased odds of unsuppressed VL, though not significant. Conclusions: HIV care encounters returned to prepandemic levels by late 2020, with sustained viral suppression. Prolonged COVID-19 restrictions were associated with higher risk of unsuppressed VL. HIV patients, providers, and clinics showed resilience during COVID-19 disruptions, offering lessons for future emergencies.

Background: The AIDS Drug Assistance Program (ADAP) supports antiretroviral therapy for low-income people with HIV. We assessed whether ADAP savings would offset additional HIV care costs resulting from new infections. Methods: Using the Joint HIV Epidemiologic and Economic Model calibrated to 30 US states and the District of Columbia, we compared continued 2025 ADAP coverage with elimination beginning Jan-2026. We projected excess HIV infections and care costs through 2035 under three cost-scenarios. Projected costs were limited to HIV care costs attributable to excess incident infections that would results from eliminating ADAP. The primary outcome was the Net Cost to Expenditure Ratio (NCER), defined as healthcare-system costs minus ADAP expenditure, relative to ADAP expenditure by 2035. Results: Across the modeled US jurisdictions, ADAP elimination was projected to result in a median of 143,347 additional HIV incident cases, generating $11.24 billion in HIV care costs through 2035. Compared with $6.58 billion in ADAP spending, this resulted in $4.66 billion in net additional costs (NCER=0.71). For every $1 in ADAP spending avoided, the healthcare system incurred $1.71 in downstream HIV care costs, a net increase of $0.71. This pattern was strongest in states with high baseline ADAP coverage and more rural HIV populations, many of which were Medicaid non-expansion states in the South, with substantial variation in NCER across jurisdictions (3.79 in Missouri to −0.97 in the District of Columbia). Conclusions: Eliminating ADAP would be medically and fiscally counterproductive, increasing HIV burden and generating healthcare costs that would exceed program savings within seven years.

Background: Weight gain is common following antiretroviral therapy (ART) initiation. Integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) have been associated with greater weight gain, though prior analyses may have been confounded by the weight-suppressive effects of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). Methods: Treatment-naive adults in the North American AIDS Cohort Collaboration on Research and Design initiating ART between 2007 and 2021 were analyzed. Predicted weight change was modeled using linear mixed effects models adjusted for demographic and clinical factors, and nucleoside reverse transcriptase inhibitor (NRTI) backbone, with subanalyses excluding EFV and stratifying by INSTI agent, NRTI, sex, and race. Results: A total of 32 514 persons were included. At 2 years, INSTIs (4.9 kg, 95% CI: 4.6–5.2) and protease inhibitors (PIs) (4.7 kg, 95% CI: 4.4–5.1) were associated with greater mean predicted weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2.7 kg, 95% CI: 2.4–2.9). Differences persisted when limiting analyses to TDF-containing regimens and excluding EFV. Among INSTIs, mean predicted weight gain was numerically highest with bictegravir (6.9 kg, 95% CI: 5.8–7.9), followed by dolutegravir (5.3 kg, 95% CI: 4.8–5.9), raltegravir (4.5 kg, 95% CI: 3.8–5.3), and elvitegravir (4.0 kg, 95% CI: 3.6–4.5). Participants receiving TAF with INSTIs gained more than those on TDF. Black females on bictegravir or dolutegravir with TAF had the highest gain at 2 years (10.0 kg, 95% CI: 7.4–12.6) Conclusions: Weight gain with non-EFV NNRTIs was lower than with PIs and INSTIs, with the greatest increases observed among Black females starting TAF with contemporary INSTIs.

Background: CD4 T cells are critical for reducing disease severity and viral clearance of SARS-CoV-2, which is particularly important among populations that are immune compromised, including people with HIV (PWH). While vaccines are effective, risk and severity of COVID-19 breakthrough infections are higher in people with vs without HIV. Little is known about the effects of SARS-CoV-2 on CD4 counts among PWH after a breakthrough infection. Methods: We evaluated the impact of COVID-19 breakthrough infection on immediate (0–60 days) and short-term (61–180 days) CD4 count from 2020 to 2022 among PWH vaccinated for COVID-19 in the CIVETs-II study (Corona-Infectious-Virus Epidemiology Team). We utilized paired t tests to test for statistically significant changes in CD4 count before and after breakthrough infection and linear mixed effect models to quantify changes in CD4 count following SARS-CoV-2 breakthrough infection. Results: Among 152 PWH, 37% were White and 40% were ≥55 years of age. Median CD4 count prebreakthrough was 614 cells/mm3, while median postbreakthrough CD4 count was 612 cells/mm3. Most patients had an undetectable HIV viral load (62%). Paired t tests indicated no change in CD4 count prior to breakthrough infection as compared with CD4 count 0 to 60 days (−40 cells/mm3; 95% CI, −86 to 5), or ≥61 days (25 cells/mm3; 95% CI, −11 to 61). Longitudinal trajectories indicated CD4 count rebound ≥61 days following breakthrough infection (112-cell/mm3 increase per 60-day increase, P < .05). Conclusions: While changes in CD4 counts were observed after breakthrough infection, these results are likely not clinically significant, suggesting that among PWH vaccinated for COVD-19, CD4 count is not substantially affected by breakthrough infections.

Plasma HIV-1 RNA viral loads (VLs) are measured via laboratory assays with changing lower limits of quantification over time. We described an approach to produce an analytic-ready dataset of VLs over time and across longitudinal cohorts of adults. A 3-step approach was used: (1) initial data cleaning, (2) data checking with visualization, and (3) final data cleaning. Assumptions, data-driven decisions, and information from cohort-specific data managers produce an analytic-ready dataset of VLs with minimal missing data for date of blood draw, HIV-1 RNA result (copies/mL), below the lower limit of quantification (BLLQ) indicator, and the lower limit of quantification (LLQ). Among 3 663 786 VLs from 186 990 participants (median number of VLs per participant = 12, interquartile range 4-27) measured from 1988 to 2021, 61% of VL records were harmonized via the 3-step approach. The proportion of VLs below the lower limit of quantification increased from 39% to 60% after application of this approach. Changes to LLQ, VL result, and BLLQ indicator variables were made to 45%, 36%, and 22% of VLs, respectively. Stated assumptions, visualized data distributions, and a documented approach to preparing an analytic-ready dataset of pooled individual-level longitudinal data revealed data idiosyncrasies, informed assumptions, and improved the data for research inference.

Background: Timely HIV diagnosis and treatment is critical to preventing transmission. The US Centers for Disease Control and Prevention (CDC) provides funding for HIV testing to local health departments and community organizations. We sought to estimate the number of additional HIV infections that would result from ending or interrupting CDC funding for HIV tests in US states. Methods: We used a validated model of HIV transmission to simulate HIV epidemics in 18 US states. We projected incidence forward under 3 scenarios where all CDC-funded HIV testing ends in October 2025 and (1) never resumes, (2) returns to previous levels between January and December 2027, and (3) returns from January to December 2029. We calculated the excess incident HIV infections compared to a scenario where CDC-funded testing continues uninterrupted. Results: If CDC funding for HIV tests were to end on 1 October 2025, we project 12 719 additional HIV infections across 18 states by 2030 (95% credible interval, 4547–21 896)—an increase of 10%. The projected effects varied by state, ranging from a 2.7% increase in Washington (1.0%–4.7%) to a 29.9 increase in Louisiana (9.4%–59.9%). States that perform more CDC-funded tests and states with more rural HIV epidemics were projected to see greater rises in incidence. Conclusions: Disruptions to CDC-funded HIV testing would substantially increase new infections, particularly in states with more rural epidemics. These findings demonstrate the value of the CDC's HIV testing activities in curbing the spread of HIV in the United States.

Importance: As the population living with HIV in the US ages, state-level projections of the aging dynamics among people with diagnosed HIV (PWDH) will be needed to inform local planning and intervention efforts. Objective: We sought to explore how aging dynamics of the population with HIV in the US are expected to differ at the state level between 2025 and 2040. Design, Setting, and Participants: We projected epidemic trajectories from 2025 to 2040 in 24 US states comprising 86% of PWDH in the US using a calibrated model of HIV transmission. Main Outcomes and Measures: We estimated change in median age of PWDH over age 13, from 2025 to 2040, for each state. Results: We project that by 2040, the median age of adult PWDH in the 24 states will rise from 51 to 62 years, and over half of adult PWDH will be over the age of 65. Our projections suggest substantial heterogeneities in age distributions by state. More populous and urban states with higher median ages of PWDH in 2025 are projected to experience even further aging of the population with diagnosed HIV in the coming 15 years. By contrast, more rural and less populous states tend to have younger-aged HIV epidemics that were not projected to age substantially over time. Conclusions and Relevance: Although the overall population of persons with diagnosed HIV in the US is projected to age substantially, these effects will unfold differently across states. In the coming years, healthcare systems will need to plan to adapt to changing state-level demographic patterns among PWDH. Key Points: Question: How will the age distribution of people living with diagnosed HIV change between 2025 and 2040? Findings: Using a calibrated model of HIV transmission in 24 US states, we project that by 2040, the median age of adult PWDH in the 24 states will rise from 51 to 62 years, and over half of adult PWDH will be over the age of 65. Our projections suggest substantial differences in age distribution by state. Meaning: In the coming years, federal and local healthcare planning will need to adapt to changing state-level demographic patterns among PWDH.

Objective: To estimate the risk of incident depressive, anxiety, psychotic disorders, and suicide attempts associated with adolescent psychotic experiences. Methods: A nested case-control design was used within the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth-cohort study that recruited expectant mothers from 1991 to 1992. Participants were 8822 offspring of ALSPAC mothers who completed the Psychosis-like Symptoms Questionnaire, which assessed Psychotic Experiences (PEs). Depressive disorders were assessed using the Short Mood and Feelings Questionnaire, anxiety disorders using the generalized anxiety disorder (GAD) Assessment and the Clinical Interview Schedule-Revised, and psychotic disorders using the PLIKS structured interviews. Risk of incident depressive disorder, GAD, psychotic disorder, and suicide attempts were compared between participants who had ever versus never reported a PE and those who reported persistent versus transient PEs. Results: Adolescent PEs were associated with increased risk for incident depressive disorder (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.42–1.84), GAD (aHR 1.23, 95% CI = 1.03–1.47), psychotic disorder (adjusted odds ratio [aOR] = 5.08, 95% CI = 2.02–12.79), and suicide attempts (aHR = 2.11, 95% CI; 1.70–2.62). Persistent PEs (compared with transient) were associated with increased risk for depressive disorder (aHR = 1.81, 95% CI = 1.55–2.12), GAD (aHR = 1.34, 95% CI = 1.07–1.68), and psychotic disorder (aOR = 7.39, 95% CI = 2.43–22.19) but not suicide attempts. Conclusion: Adolescent PEs are a risk factor for multiple mental disorders and suicide attempts, with persistent PEs conferring greater risk. Identifying interventions for adolescents who report PEs, particularly persistent PEs, could lessen the burden of multiple mental health disorders and suicide attempts.