While poverty is an established barrier to achieving success at each step of the HIV care continuum, less is known about specific aspects of poverty and how they overlap with behavior in exceptionally low-income individuals who live in well-resourced areas. We considered unsuppressed viral load over 3 years among women living with HIV in San Francisco who used homeless shelters, low-income hotels and free meal programs. One-hundred twenty study participants were followed; 60% had > 1 unsuppressed viral load and 19% were unsuppressed at every visit. Across six-month intervals, the odds of unsuppressed viral load were 11% higher for every 10 nights spent sleeping on the street [Adjusted Odds Ratio (AOR) 1.11, 95% CI 1.02-1.20]; 16% higher for every 10 nights spent sleeping in a shelter (AOR/10 nights 1.16, 95% CI 1.06-1.27); 4% higher for every 10 nights spent sleeping in a single-room occupancy hotel (AOR/10 nights 1.04, 95% CI 1.02-1.07); and over threefold higher among women who experienced any recent incarceration (AOR 3.56, 95% CI 1.84-6.86). Violence and recent use of outpatient health care did not significantly predict viral suppression in adjusted analysis. While strategies to promote retention in care are important for vulnerable persons living with HIV, they are insufficient to ensure sustained viral suppression in low-income women experiencing homelessness and incarceration. Results presented here in combination with prior research linking incarceration to homelessness among women indicate that tailored interventions, which not only consider but prioritize affordable housing, are critical to achieving sustained viral suppression in low-income women living with HIV.

Background

Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.

Methods

A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.

Results

Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.

Conclusions

An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.

Background

Lifelong antiretroviral therapy (ART) is recommended for all HIV-infected pregnant women, but early studies suggest that women often drop out of care postpartum and data are limited on virologic outcomes.

Methods

We evaluated viral suppression (primary outcome) and retention in care up to 5 years after ART initiation among HIV-infected women who started lifelong ART during pregnancy, irrespective of CD4 count, in a study in rural Uganda (NCT00993031). Participants were followed in the study for up to 1 year postpartum, then referred to clinics in surrounding communities. A random sample (N = 200) was invited to participate in a cross-sectional follow-up study after completing the trial, involving one visit for a questionnaire and pregnancy and HIV-1 RNA testing. Retention in care was defined as having attended an HIV clinic in the last 90 days. Logistic regression models were used to examine factors associated with viral suppression (HIV-1 RNA <400 copies/ml) at follow-up.

Results

One hundred fifty women (75%) were successfully contacted for follow-up at a median of 4.2 years after starting ART; 135 were retained in care [90%, 95% confidence interval (CI): 84.0% to 94.3%] and 121 demonstrated viral suppression (80.7%, 95% CI: 73.4% to 86.7%). Women who had disclosed their HIV status to their primary partner had greater odds of viral suppression (adjusted odds ratio: 4.51, 95% CI: 1.02 to 19.8).

Conclusions

High rates of viral suppression can be achieved up to 5 years after initiating ART during pregnancy among women retained in care. Interventions to facilitate disclosure may improve long-term outcomes among women who initiate ART during pregnancy under universal treatment.

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Introduction

Geographic and transportation barriers are associated with poorer HIV-related health outcomes in sub-Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation-related barriers on pre-exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).

Methods

Community-wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV-discordant partner, or self-referral at either the community health campaign or during home-based testing from March to April 2017. We collected data from PrEP-eligible households on GPS-measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi-quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP-eligible individuals and (2) four-week clinic visit attendance among PrEP initiators.

Results

Of the 701 PrEP-eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home-based testing and did not have the option of same-day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to take PrEP every day" (N = 18) and "low/no risk of getting HIV" (N = 18). Transportation-related barriers, including "clinic is too far away" (N = 6) and "travel away from home" (N = 4) were also reported.

Conclusions

Distance to clinic is a significant predictor of PrEP uptake and four-week follow-up visit attendance in a community in rural Uganda. Interventions that address geographic and transportation barriers may improve PrEP uptake and retention in sub-Saharan Africa.

BACKGROUND: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. METHODS: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. RESULTS: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. CONCLUSIONS: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Background

Pregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care.

Setting

Rural Kenya and Uganda.

Methods

Women (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation.

Results

Between April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001).

Conclusion

A person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.

Background

Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies.

Methods

To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes using 2 cohorts of patients with S. aureus bacteremia (n = 32 and n = 124).

Results

We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia. Prognostic modeling identified interleukin (IL)-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers classifying fatal outcome with 89% sensitivity and 77% specificity (P < .0001). Baseline IL-17A levels were elevated in patients with persistent bacteremia (P < .0001), endovascular (P = .026) and metastatic tissue infections (P = .012).

Conclusions

These results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials.

Background

Young men-who-have-sex-with-men (MSM) are disproportionately impacted by human immunodeficiency virus (HIV). Preexposure prophylaxis (PrEP) could reduce HIV acquisition among youth, but suboptimal adherence threatens effectiveness. Optimal metrics of PrEP adherence among adolescents have remain undefined.

Methods

The Adolescent Trials Network 110/113 studies provided daily oral PrEP with tenofovir (TFV) disoproxil fumarate/emtricitabine over 48 weeks to a diverse population of MSM (aged 15-22 years). Self-reported adherence was assessed and PrEP drug concentrations measured from hair and dried blood spot (DBS) samples; 23% of participants received Wisepill electronic monitoring devices. The average number of PrEP doses per week taken was estimated, and concordance between measures assessed.

Results

Among 243 participants, hair samples were collected at 1186/1238 (96%) person-visits. The concordance of TFV levels in hair and TFV-diphosphate in DBS around thresholds consistent with taking ≥4 and 7 PrEP doses/week was high (76% and 80%). Hair and DBS concentrations correlated poorly with self-report and Wisepill metrics. Through week 12, 40%-60% of participants (by hair and DBS), ≤31% (Wisepill), and >85% (self-report) were estimated to have taken ≥4 PrEP doses/week (a threshold associated with protection among MSM). For all measures except self-report, adherence declined over time, with half of participants taking <2 doses/week by week 48.

Conclusions

Among youth on PrEP, adherence waned over time. Self-report overestimated adherence, and use of Wisepill was limited. Hair collection was highly acceptable and provided similar interpretations to DBS. Incorporation of either metric in future PrEP studies among youth could identify suboptimal adherence and trigger interventions.