Background: Direct oral anticoagulants such as rivaroxaban are a feasible and convenient option for anticoagulation in people living with HIV. Here, we assess the effect of cobicistat or darunavir/cobicistat on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of rivaroxaban. Methods: This open-label, fixed sequence, intrasubject drug-drug interaction PK study enrolled healthy participants who received oral study drugs sequentially as follows: rivaroxaban 10 mg once on day 1, cobicistat 150 mg once-daily on days 2 to 7, rivaroxaban 10 mg once on day 7, darunavir/cobicistat 800/150 mg once-daily on days 8 to 13 followed by rivaroxaban 10 mg once on day 13. Serial PK and PD plasma samples were obtained on days 1, 7, and 13 over 24 hours. Safety was assessed throughout the study. Results: Twelve participants enrolled and completed three phases of the study. Rivaroxaban geometric mean ratios (GMR, rivaroxaban + cobicistat versus rivaroxaban alone) and 90% confidence interval (CI) for C max and AUC 0-∞ were 1.50 (1.10-1.90) and 2.14 (1.70-2.58), respectively. Rivaroxaban GMR (rivaroxaban + darunavir/cobicistat versus rivaroxaban alone) and 90% CI for C max and AUC 0-∞ were 1.53 (1.13-1.94) and 2.12 (1.68-2.56), respectively. Rivaroxaban concentrations were positively correlated with PD markers in a linear fashion and returned to near-baseline 24 hours post-dose. All adverse events were mild to moderate in severity and resolved by the end of the study. Conclusion: Coadministration of cobicistat and cobicistat-boosted darunavir with rivaroxaban resulted in a clinically significant increase in rivaroxaban drug exposure. Further study can inform safety and efficacy of rivaroxaban dose reduction.
Background: In the US, the Veterans Health Administration is the largest single institutional provider of Human Immunodeficiency Virus (HIV) care for veterans. Retention in care can affect treatment adherence and care outcomes. Psychiatric disorders are prevalent in people with HIV and may lead to poorer retention in care and outcomes. Objectives: To examine the association between retention in HIV care, psychiatric comorbidities, and clinical outcomes among veterans with HIV. Research Design: In this retrospective study, veterans aged ≥18, seen with a diagnosis of HIV between 2000 and 2017, were identified from the Corporate Data Warehouse. We identified those with and without psychiatric comorbidities in the HIV cohort. Outcomes (mortality, viral suppression, and inpatient and outpatient visits) were assessed over a five-year follow-up period. Retention in care was measured during the first year of follow-up. We modeled outcomes as a function of retention in care and tested the moderating effects of psychiatric comorbidity and treatment for psychiatric comorbidity. Results: Cohort consisted of 59,649 veterans with a diagnosis of HIV; 66% had psychiatric comorbidity, and 90% received treatment for it. Overall, 49% were retained in HIV care. Retention in care was associated with better survival and viral suppression, regardless of psychiatric comorbidity; however, psychiatric comorbidity influenced healthcare utilization. Conclusions: Our study provides important insights into the relationship between retention in care, psychiatric comorbidity, and outcomes in veterans with HIV. Future research must assess the barriers to care and strategies to integrate mental health and HIV treatments for veterans.
INTRODUCTION:Steatotic liver disease (SLD) is highly prevalent in people with HIV (PWH) and is a major cause of morbidity and mortality in this population. However, it remains unclear whether SLD is influenced by HIV infection and whether the clinical management of PWH who have SLD should differ from non-HIV populations. METHODS:Liver steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) among 1,580 women (1,117 with HIV; 463 without) enrolled in the Women's Interagency HIV Study between 2013 and 2018. Steatosis was defined by a controlled attenuation parameter (CAP) ≥248 dB/m, and clinically significant fibrosis by liver stiffness ≥7.1 kPa. Participants were classified according to the AASLD diagnostic algorithm for SLD. Differences in fibrosis prevalence by HIV status were evaluated, and multivariable logistic regression was performed to identify factors associated with SLD and fibrosis, adjusting for age, ethnicity, BMI, alcohol use, diabetes, and smoking. RESULTS:Prevalence of SLD was 740 of 1580 (47%) and did not differ by HIV serostatus. Most SLD was metabolic dysfunction-associated steatotic liver disease (MASLD; 629 of 740 [82%]). HIV infection was associated with higher odds of clinically significant fibrosis only among women with SLD (adjusted OR 1.48, 95% CI 1.01-2.16, p=0.04; HIV*SLD interaction among entire cohort p=0.03). DISCUSSION:In this study, most SLD in women living with HIV is classified as MASLD. HIV infection is associated with higher odds of hepatic fibrosis only among those with SLD. Further work is needed to understand how HIV may potentiate fibrosis in the setting of SLD.
BACKGROUND:Biomarkers provide reliable information on oral PrEP pill-taking. It remains unclear whether self-reported PrEP adherence has value when used in combination with pharmacologic measures. We examined associations between self-reported and biomarker-based PrEP adherence metrics to improve identification of those with low adherence in resource-constrained settings. METHODS:HIV-uninfected women using oral tenofovir (TFV)-based PrEP were enrolled (N=100) in the Point-of-Care Urine Monitoring for Adherence trial in Kenya from 2021-2022. Participants were randomized 1:1 to standard-of-care or urine-based-point-of-care assay-informed drug-level feedback. Adherence was measured at enrollment and quarterly through 12 months via urine, hair and self-report. A positive urine assay (TFV≥1500 ng/mL) indicated short-term adherence. TFV hair concentration≥0.023 ng/mg indicated long-term adherence (4-times-weekly dosing). Self-reported adherence was calculated as the mean score (range=0-100) on a 2-item scale. Generalized estimating equations estimated longitudinal associations between self-reported adherence and biomarkers. Receiver-operating-characteristic curves assessed self-report as a predictor of biomarker metrics. RESULTS:At enrollment, 68.7% had a positive urine assay, 83.7% had detectable hair TFV, and median self-reported adherence was 100 (IQR=90-100). At Month 12, participants with higher adherence scores were more likely to have hair TFV concentrations≥0.023 ng/mg (aRR=1.44; 95% CI=1.20-1.72; p-value<0.001) and positive urine results (aRR=1.56; CI=1.43-1.69; p-value=<0.001). Areas-under-the-curve for self-report as a predictor of hair levels were 0.64 in a model with self-report and 0.74 in a model with both self-report and urine testing. CONCLUSIONS:Associations between self-reported and biomarker-verified PrEP adherence demonstrated accurate reporting. Incorporating biomarkers in studies may result in improved adherence and/or improved accuracy of self-report.
BACKGROUND:Long-acting injectable antiretroviral therapy (LA-ART) has enormous potential benefit for increasing viral suppression among persons with HIV (PWH). SETTING:U.S. HIV care facilities. METHODS:We analyzed data on past 12-month LA-ART prescriptions collected over 3 annual data collection cycles (2021-2023) from probability samples of U.S. adults with HIV (collected 6/1/2021-5/30/2024, N=11,524). We report weighted percentages of PWH prescribed LA-ART and use prevalence ratios (PRs) with predicted marginal means and 95% confidence intervals (CIs) to quantify differences in prescription of LA-ART over time and between groups. RESULTS:The percentage of PWH prescribed LA-ART increased from 0.4% (CI 0.2-0.7) in the 2021 cycle to 3.4% (CI 2.8-3.9) in the 2023 cycle (PR 7.8 [CI 4.5-13.6]). During the 2022-2023 cycles, prescription of LA-ART was higher among those living in Northeastern Medical Monitoring Project (MMP) states versus Southern MMP states (3.4% [CI 2.4-4.3] vs. 1.9% [CI 1.3-2.5], PR 1.8 [1.2-2.8]) and those receiving care at Ryan White HIV/AIDS program (RWHAP)-funded versus non-funded facilities (2.9% [CI 2.4-3.4] vs. 1.8% [CI 1.3-2.4], PR 1.6 [CI 1.1-2.2]). Older age (>50 vs. <40 years) was also associated with lower ART prescription. CONCLUSION:Prescription of LA-ART is increasing among U.S. adults with HIV, though prevalence remains low. LA-ART uptake lagged in the South, where HIV infections and negative health outcomes are disproportionately high. Comprehensive HIV care delivery-such as found in RWHAP-facilities-may facilitate LA-ART adoption.
BACKGROUND:Arts-based sexual health workshops may improve adolescent sexual health, yet limited studies have evaluated outcome trends over time. This study examined HIV prevention outcomes before and after school-based workshop participation among adolescents in the Northwest Territories (NWT), Canada. METHODS:We analyzed seven waves of pretest and immediate posttest data from adolescents aged 13-18 years in 17 NWT communities from 2018-2019 to 2024-2025. Surveys assessed sociodemographic characteristics, HIV knowledge, and condom use self-efficacy (CUSE). Paired-samples t-tests examined pretest to posttest differences. Mixed-effects linear regression models examined trends in change scores across school years and adjusted for the number of previously completed arts-based sexual health workshops. RESULTS:The pretest sample included 1,936 workshop observations; 1,579 had paired outcome data. Mean age was 13.64 years (SD=1.47); 48.86% were cisgender girls, 19.62% identified as lesbian, gay, bisexual, or queer, 70.05% identified as Indigenous, and 68.16% lived outside of Yellowknife in rural settings. HIV knowledge increased from 2.74 (SD=3.13) to 8.05 (SD=4.18), with a large effect size (Cohen's dz=1.30). CUSE increased from 19.59 (SD=4.40) to 20.32 (SD=4.70), with a small effect size (Cohen's dz=0.15). HIV knowledge gains increased across school years, particularly among older adolescents and cisgender girls. CUSE gains also increased; no sociodemographic interaction was statistically significant. CONCLUSION:Arts-based sexual health workshop participation was associated with immediate improvements in HIV knowledge and CUSE across seven school years among Northern and Indigenous adolescents in the NWT. Findings support continued evaluation of culturally responsive, arts-based HIV prevention in Northern and remote settings.
Background: Little is known of condom use self-efficacy (CUSE) trajectories over time and associations with HIV prevention engagement. We examined longitudinal associations between CUSE trajectories and HIV prevention engagement, and the mediating role of HIV-related stigma, among urban refugee youth in Kampala, Uganda. Methods: This cohort study with refugee youth in Kampala collected data at three timepoints from 2022 to 2024. We conducted latent class growth analysis (LCGA) to identify distinct CUSE trajectories over time. We then conducted path analysis to explore associations between CUSE trajectory classes and HIV prevention engagement (lifetime HIV/ STI testing, HIV self-testing [HIV-ST] uptake and awareness, recent condom use), examining the mediating role of HIV-related stigma. Results: We included 176 participants (mean age: 21.0, standard deviation: 2.5; 51.7% women, 48.3% men) with 520 observations. Two latent CUSE trajectories were identified: persistently high (n=451; 86.7%) and sustained low (n=69; 13.3%). In the direct effect model, higher CUSE trajectory scores were associated with increased lifetime STI testing, HIV-ST uptake and awareness, and recent condom use. In the indirect effect model including HIV-related stigma: a) HIV-related stigma partially mediated the associations between the high CUSE trajectory and lifetime STI testing, and b) HIV-related stigma was associated with reduced HIV-ST uptake and awareness and reduced recent condom use, even in the high CUSE trajectory class. Conclusions: Higher CUSE trajectories were associated with improved HIV prevention engagement, yet HIV-related stigma attenuated these associations. While CUSE is important for HIV prevention agency, sustained attention to HIV-related stigma reduction is necessary.
Background: Criminal legal involved (CLI) persons who use drugs (PWUD) are at high risk of exposure to HIV, yet few initiate pre-exposure prophylaxis (PrEP). Understanding interest in PrEP and the different formulations of PrEP may improve uptake in this population. Methods: Participants were CLI adults aged 18 or older, used opioids and/ stimulants, tested negative for HIV and met CDC PrEP eligibility criteria. Characteristics of persons interested in PrEP were compared to those who were not interested in PrEP at baseline. Among those interested in PrEP, characteristics were compared for those who preferred long-acting injectable (LAI) versus oral PrEP. Results: Of 566 persons enrolled, 35.1% (N=199) were interested in PrEP; of those, 60.8% (N=121) preferred LAI vs 39.1% (N=78) oral PrEP. PrEP interest was greater in persons from Texas (50%) vs Connecticut (18.3%). A significantly higher odds of being interested in PrEP was associated with having a methamphetamine use disorder and a higher self-perceived risk of HIV; and a history of sharing IDU equipment was associated with a higher odds of being interested in LAI vs. oral PrEP. Conclusions: Among CLI PWUD eligible for PrEP, persons in TX, were more interested in PrEP compared to persons in CT. Persons with a methamphetamine use disorder and a higher self-perceived risk of HIV were predictors of PrEP interest and sharing IDU equipment was a predictor of interest in LAI vs. oral PrEP. More research on patient choice and shared decision making should be included to improve PrEP initiation.
Background: Weight gain in people with HIV (PWH) has generated concern regarding metabolic consequences of antiretroviral therapy (ART). It is unclear whether weight gain differs between virally suppressed (VS) PWH and people without HIV (PWoH) when accounting for key characteristics, or which clinical and demographic factors drive weight gain in VS PWH. Methods: This retrospective observational cohort study utilized electronic records from 12 US federally qualified health centers (January 2015-August 2023). Part A employed multi-stage propensity score matching (4:1 ratio) to compare 3-year weight trajectories adjusting for demographics, comorbidities, and medications. Part B used classification and regression trees (CART), logistic regression to identify predictors of weight gain (≥10% gain with BMI shift or baseline obesity) vs minimal gain (>0% to <5%) among 10,413 suppressed PWH. Results: In matched, adjusted analyses (1,296 VS PWH; 4,168 matched PWoH), no significant difference in mean 3-year weight change was observed between VS PWH and PWoH (0.4 kg, 95% CI: -0.1 to +0.9). A higher proportion of VS PWH gained ≥10% of baseline weight compared to PWoH (15% vs. 11%, p<0.001) and increased BMI shifts (13% vs. 11%, p=0.02). Among virally suppressed PWH, significant gain correlated with younger age (median 44 vs. 51 years), female sex (28% vs. 16%), Black race (49% vs. 37%), and lower baseline BMI. No ART regimen were associated with significant weight gain . Conclusion: Weight change in suppressed PWH are similar to those of matched PWoH. Clinical and sociodemographic characteristics, not ART regimens, correlated with 3-year gain in VS PWH.
BACKGROUND:Adolescents and young adults living with HIV (AYAHIV) aged 15-24 years experience poorer HIV outcomes than other age groups, with frequent interruptions from care. Interruptions during the first year of antiretroviral therapy (ART) are especially concerning, as they occur before sustained viral suppression. We estimated the incidence of early HIV care interruption and associated factors among AYAHIV initiating ART in the Khayelitsha cohort, Western Cape, South Africa. METHODS:We conducted a retrospective cohort study of AYAHIV initiating ART between 2017 and 2021. Early HIV care interruption was defined as ≥90 days late for a scheduled refill without documented death or transfer. Participants were followed for 12-15 months. Cox proportional hazards models assessed associated factors, adjusting for age, sex, calendar year, dispensing interval (single-month vs multi-month), and regimen among 2020-2021 initiators. A sensitivity analysis was restricted to those with ≥4 refills. RESULTS:Among 5,149 AYAHIV (85% female; median age 23 years), 44% experienced early interruption, most within six months. Initiation in 2020 (adjusted Hazard ratio (aHR): 1.10, 95% confidence interval (95% CI): 1.03, 1.17) and 2021 (aHR: 1.28 95% CI: 1.18, 1.39) was associated with increased interruption risk versus 2017-2019. Dolutegravir was associated with a reduced risk compared to efavirenz (aHR: 0.87 95% CI: 0.78, 0.97). In sensitivity analyses (n=3,013), 32% interrupted, with similar associations. CONCLUSIONS:Early HIV care interruption was common, particularly during COVID-19. Dolutegravir was associated with improved retention, yet substantial early interruptions persisted, highlighting the need for intensified youth-focused support following ART initiation.
BACKGROUND:To better understand HIV and cardiovascular disease (CVD) effects on brain white matter during HIV infection, advanced diffusion imaging and comprehensive predictor analyses are essential. SETTING:Prospective observational cohort study. METHOD:84 virally suppressed people with HIV infection (PWH) and 48 uninfected controls underwent T1-weighted, FLAIR, and diffusion MRI at baseline and 24 months later (75 PWH and 40 controls). White Matter Hyperintensity (WMH) volumes were derived from structural scans. Fixel-based analysis tract-based metrics included fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC). RESULTS:Relative to controls, mixed models showed significant reductions (p<.05 - p<.01) of FC, and lower FDC to a lesser extent, in multiple long cortical association tracts, and within striatal- and thalamic-frontoparietal connections in PWH at both time points. Higher CVD risk was associated with reduced FC in the arcuate fasciculus and FDC in the cingulate gyrus (p<.05). In PWH, more severe cognitive impairment and longer duration of HIV disease was associated with worse FDC across multiple tracts (p<.03 - p<.001). Lower baseline CD4 counts was associated with lower FD in the frontal association tracts (p<.05 - p<.005). Higher WMH volume was associated with higher CVD risk (periventricular p<.001, deep p<.03), but not HIV status. CONCLUSIONS:Major brain white matter tracts are impacted by HIV status, HIV duration, cognitive impairment, baseline CD4, and CVD risk to a lesser extent, despite equal WMH burden between infection groups. Our study provides further evidence of active immuno-vascular underpinning of HIV neuropathogenesis on fine white matter structure despite controlled HIV.
BACKGROUND:People with HIV (PWH) are living longer due to effective antiretroviral therapy (ART) but face accelerated aging, accumulating comorbidities, and high rates of polypharmacy. Whether neuroinflammatory biomarkers are associated with polypharmacy and adverse clinical outcomes such as falls in this population is unknown. METHODS:We performed a cross-sectional analysis of baseline data from 600 virally suppressed PWH ≥40 years enrolled in the ACTG A5322 HAILO cohort. Plasma neurofilament light chain (NfL), neopterin, and soluble CD14 (sCD14) were measured. Multivariable logistic regression examined associations between each biomarker and polypharmacy (five or more non-ART medications), recurrent falls (two or more falls/6 months), and slow gait speed less than one m/s), adjusting for age, sex, and comorbidity burden. RESULTS:The median age was 54 years, 78% of participants were male, and 232 participants (39%) had polypharmacy. Elevated NfL was independently associated with polypharmacy in multivariable analysis (aOR 1.16 [95% CI 1.07-1.26]). In the total population, elevated NfL (OR 1.24 [1.05-1.46]) and sCD14 (OR 1.12 [1.01-1.23]) were each associated with recurrent falls. Among participants with polypharmacy, only elevated sCD14 remained associated with recurrent falls on stratified multivariable analysis (OR 1.15 [1.02-1.30]). No biomarker was significantly associated with slow gait speed. CONCLUSIONS:In older virally suppressed PWH, plasma NfL and sCD14 are associated with distinct adverse clinical phenotypes-medication burden and fall risk, respectively, and may serve as complementary biomarkers of distinct biological pathways relevant to aging in HIV.
BACKGROUND:COVID-19 and HIV infection are independently associated with increased risk of adverse pregnancy outcomes. However, there is limited evidence on the impact of SARS-CoV-2 infection during pregnancy in sub-Saharan Africa, particularly among women living with HIV (WLWH). SETTING:Two antenatal clinics in southern Malawi (2018 - 2022). METHODS:We conducted a prospective cohort study of singleton pregnancies enrolled at 20-36 weeks gestation. SARS-CoV-2 infection was determined via serologic testing at enrollment and delivery. Participants were enrolled based on HIV status and viral suppression: (1)WLWH with detectable viral load (VL), (2)WLWH with undetectable VL, and (3)HIV-negative women. We used multivariable logistic regression with adjustment for confounding to evaluate the impact of SARS-CoV-2 alone or in combination with HIV infection on the following adverse birth outcomes: low birth weight (LBW), preterm birth, small-for-gestational-age (SGA), and stillbirth or early neonatal death. RESULTS:Among 905 pregnant women, 29% tested positive for SARS-CoV-2, 87% of infections were mild or asymptomatic. Overall, SARS-CoV-2 infection was significantly associated with SGA births (adjusted OR [aOR]: 1.49, 95% CI: 1.03-2.13) but not associated with other adverse outcomes. Among WLWH, SARS-CoV-2 was significantly associated with increased odds of LBW (aOR: 2.07, 1.10-3.91) and SGA births (aOR: 1.73, 1.01 - 2.91). The effect of SARS-CoV-2 infection among WLWH did not differ based on VL. CONCLUSION:SARS-CoV-2 infection during pregnancy was associated with adverse birth outcomes, particularly among WLWH. These findings underscore the need for integrated antenatal care and targeted infection prevention strategies for pregnant women with HIV in high-burden settings.
Background: Safe and effective antiretrovirals (ARVs) are essential for managing HIV-1 in pregnant individuals and ensuring positive pregnancy outcomes. International guidelines recommend dolutegravir-based regimens as the preferred option for pregnant individuals or those planning to conceive. Setting: The Antiretroviral Pregnancy Registry (APR) is a voluntary, international, prospective, exposure-registration cohort study providing early warning signals of major teratogenicity with ARV use. Methods: Pregnancy and neonatal outcomes following prenatal dolutegravir exposure were assessed among prospectively reported pregnancies starting in 2013, after dolutegravir approval for HIV-1 treatment, through January 31, 2025. Birth defect prevalence after first-trimester dolutegravir exposure was compared with prevalence during the second and third trimesters, for other ARVs, and the general US population. Results: Among 2075 pregnancies exposed to dolutegravir, initial exposure occurred during periconception, later first trimester, second trimester, and third trimester in 53%, 14%, 24%, and 9% of pregnancies, respectively. Overall, 93% (1970/2127) of pregnancy outcomes resulted in live births. Birth defect prevalence after first-trimester dolutegravir exposure was 3.3% (95% CI, 2.4%-4.4%), which was comparable to rates for other ARVs and the general US population. A single neural tube defect (anencephaly) was reported among pregnancies with earliest dolutegravir exposure during periconception, corresponding to a prevalence of 0.1% (1/1120). Among the 1802 singleton live births without defects, 89% (n=1605) were delivered at ≥37 weeks of gestation, and 85% (n=1540) had a birth weight ≥2500 g. Conclusion: Findings confirm the safety of prenatal dolutegravir exposure and reinforce dolutegravir-based regimens as safe options for all people of childbearing potential.
The life-prolonging benefits of antiretroviral therapy (ART) are undermined by poor retention in care and suboptimal ART adherence. While behavioral interventions have demonstrated efficacy in clinical trials and are widely disseminated, scaling-up of evidence-based interventions is hampered by not knowing answers to basic implementation questions, such as the minimally effective dose (MED) of counseling and how the MED varies across patients. This trial aimed to answer these questions. People living with HIV in the southeastern US (N = 295) who were either not engaged in care, non-adherent (<85%) to ART or HIV unsuppressed participated in a dose determination trial designed to: (a) find the MED of counseling sessions for missed care appointments, ART adherence, and HIV suppression and (b) the moderators of dose over 12-months of observation. We found that 31% of participants did not complete more than two sessions (i.e., early dropout) of counseling. The MED for behavioral counseling on HIV care, adherence and viral load was 5 sessions, with an MED range of 4-6 depending on counseling facilitators (e.g., social support) and barriers (e.g., medication concerns). Behavioral counseling in previous trials may have been under-dosed when delivered in fewer than 5 sessions and over-dosed when delivered in greater than 6 sessions, depending on patient characteristics that moderate dose-response relationships.
CDC and state/local health departments analyze HIV sequences to identify molecular clusters representing rapid transmission. Local analyses can be timelier, but are limited to sequences available in the local surveillance system, and thus may miss all or part of clusters spanning multiple jurisdictions. We assessed the added value of national analyses for clusters missed or only partially detected by local analyses. We reviewed national quarterly analyses of HIV sequences (September 2021 – June 2023) that identified priority clusters (defined as ≥5 diagnoses in the past 12 months within a genetic distance of ≤0.005 substitutions per site among people with HIV diagnosed during the most recent three years). For each cluster, we simulated whether and when single-jurisdiction analysis would meet priority threshold and calculated the proportion of cluster members that could be identified locally. Of 149 clusters detected in the national analysis, 91 (61%) clusters would have been detected concurrently by local analysis, 27 (18%) would have delayed detection (median: 59 days), and 31 (21%) would not have been detected locally. In clusters detected by both approaches, an average of 91% of cluster members identified in the national analysis would have also been identified in the local analysis. National analyses detected clusters that local analyses missed, identified additional cluster members, and found certain clusters earlier. National cluster detection plays a vital role in enhancing local detection activities.
Background: Human papillomavirus bivalent (2vHPV) and nonavalent (9vHPV) vaccines protect against HPV types causing 70% and 90% of cervical cancers, respectively. South African guidelines recommend vaccinating girls ages 9-14 with one dose of 2vHPV. Switching recommendations to 9vHPV could avert more cervical cancer burden, but the cost-effectiveness and cost-threshold of 9vHPV in South Africa is unknown. Methods: Using a validated compartmental HPV and HIV transmission model parameterized to KwaZulu-Natal, South Africa, we simulated scenarios of 2vHPV and 9vHPV implementation over 100 years with two doses (72% coverage) and one dose (80% and 90% coverage) with lifelong or waning single-dose vaccine efficacy. We evaluated cervical cancer cases and deaths averted. We also estimated the maximum cost/dose for 9vHPV to be cost-effective using willingness-to-pay thresholds from $500/DALY averted to $3,015/DALY averted (2023 USD). We also assessed the incremental cost-effectiveness ratios (ICERs) of 9vHPV at current costs ($110/dose) compared to 2vHPV ($9.23/dose). Results: Single-dose 9vHPV at 80% coverage could avert 7.9% more cervical cancer cases and 6.4% more deaths than 2vHPV (lifelong efficacy). The maximum 9vHPV price to be cost-effective (lifelong efficacy, 80% coverage) ranged from $15 ($500/DALY averted threshold) to $45/dose ($3,015/DALY averted threshold). At current market costs, single-dose 9vHPV at 90% coverage exceeds commonly used cost-effective thresholds with ICERs of $10,480/DALY averted (lifelong efficacy) and $8,806/DALY averted (waning efficacy). Conclusion: Implementing 9vHPV can result in a greater reduction in cervical cancer burden than 2vHPV, but vaccine costs need to be reduced for 9vHPV to be cost-effective in KwaZulu-Natal.
