Costs of home-delivered antiretroviral therapy refills for persons living with HIV: evidence from a pilot randomized controlled trial in KwaZulu-Natal, South Africa.

Antiretroviral therapy (ART) is needed across the lifetime to maintain viral suppression for people living with HIV. In South Africa, obstacles to reliable access to ART persist and are magnified in rural areas, where HIV services are also typically costlier to deliver. A recent pilot randomized study (the Deliver Health Study) found that home-delivered ART refills, provided at a low user fee, effectively overcame logistical barriers to access and improved clinical outcomes in rural South Africa. In the present costing study using the payer perspective, we conducted retrospective activity-based micro-costing of home-delivered ART within the Deliver Health Study and when provided at-scale (in a rural setting), and compared to facility-based costs using provincial expenditure data (covering both rural and urban settings). Within the context of the pilot Deliver Health Study which had an average of three deliveries per day for three days a week, home-delivered ART cost (in 2022 USD) $794 in the first year and $714 for subsequent years per client after subtracting client fees, compared with $167 per client in provincial clinic-based care. We estimated that home-delivered ART can reasonably be scaled up to 12 home deliveries per day for five days per week in the rural setting. When delivered at scale, home-delivered ART cost $267 in the first year and $183 for subsequent years per client. Average costs of home delivery further decreased when increasing the duration of refills from three-months to six- and 12-month scripts (from $183 to $177 and $135 per client, respectively). Personnel costs were the largest cost for home-delivered refills while ART drug costs were the largest cost of clinic-based refills. When provided at scale, home-delivered ART in a rural setting not only offers clinical benefits for a hard-to-reach population but is also comparable in cost to the provincial standard of care.

Estimating the Effect of COVID-19 Pandemic Restrictions on Self-reported Antiretroviral Therapy Use and Late Refill Visits Among People Living With HIV in Rural South Africa.

BACKGROUND: People living with HIV require reliable access to and adequate supply of antiretroviral therapy (ART) for viral suppression. The Deliver Health Study, a randomized trial conducted during the COVID-19 pandemic, found that home-delivered ART significantly increased viral suppression compared with clinic-based care. The effect of changing COVID-19 alert levels on self-reported ART use has not been quantified. SETTING: KwaZulu-Natal, South Africa. METHODS: Adults living with HIV were followed in the Deliver Health Study during October 2019-December 2020. We used difference-in-differences (DiD) to estimate the effect of changing COVID-19 alert levels during 3 distinct periods on self-reported missed ART doses (missed 0 vs. ≥1 doses in past week) for participants receiving home-delivered vs. clinic-based refills. We additionally estimated the effect of changing COVID-19 alert levels on late clinic ART refill visits (late vs. on-time). We used relative risk regression for both binary outcomes. RESULTS: Of 155 participants, 46% were women and the median age was 36 years. The mean number of missed weekly doses was 0.11, 0, and 0.12 in the home-delivery group and 0.09, 0.08, and 0.18 in the clinic group during periods 1, 2, and 3, respectively. There were no differences in relative risk of self-reported daily ART use between refill groups when comparing across periods [DiDperiod 2 vs. 1 = 1.05; 95% confidence interval: 0.97, 1.13 and DiDperiod 3 vs. 2 = 0.99; 95% confidence interval (CI): 0.91, 1.08]. In the clinic group, the risk of late refill visits was significantly higher during COVID-19 restrictions (vs. before alert level 5 implementation) and even after the COVID-19 alert level was downgraded to level 1 (RRperiod 2 vs. 1 = 1.83, 95% CI: 1.34, 2.51 and RRperiod 3 vs. 2 = 1.71; 95% CI: 1.43, 2.04). CONCLUSION: The COVID-19 pandemic did not differentially impact self-reported ART adherence by the method of ART refills, but the risk of late clinic refill visits was significantly higher during COVID-19 restrictions and sustained after restrictions were loosened.

Modeled estimates of HIV-serodifferent couples in tuberculosis-affected households in four sub-Saharan African countries.

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions.

Virologic Nonsuppression and HIV Drug Resistance Among People Who Inject Drugs and Their Sexual and Injecting Partners in Kenya.

We evaluated the prevalence and correlates of HIV viral nonsuppression and HIV drug resistance (HIV-DR) in a cohort of people who inject drugs living with HIV (PWID-LH) and their sexual and injecting partners living with HIV in Kenya. HIV-DR testing was performed on participants with viral nonsuppression. Of 859 PWID-LH and their partners, 623 (72.5%) were on antiretroviral therapy (ART) ≥4 months and 148/623 (23.8%) were not virally suppressed. Viral nonsuppression was more common among younger participants and those on ART for a shorter duration. Among 122/148 (82.4%) successfully sequenced samples, 55 (45.1%) had detectable major HIV-DR mutations, mainly to non-nucleoside and nucleotide reverse transcriptase inhibitors (NNRTI and NRTI). High levels of HIV-DR among those with viral nonsuppression suggests need for viral load monitoring, adherence counseling, and timely switching to alternate ART regimens in this key population.

Study of heavy metal resistance genes in Escherichia coli isolates from a marine ecosystem with a history of environmental pollution (arsenic, cadmium, copper, and mercury).

We analyzed whole genome sequences of 308 Escherichia coli isolates from a marine ecosystem to determine the prevalence and relationships of heavy metal resistance genes (HMRGs) and antibiotic resistance genes (ARGs), as well as the presence of plasmid sequences. We screened all genomes for presence of 18 functional HMRGs conferring resistance to arsenic, cadmium, copper, or cadmium/mercury. In subset analyses, we examined geographic variations of HMRG carriage patterns in 224 isolates from water sources, and sought genetic linkages between HMRGs and ARGs in 25 genomes of isolates resistant to antibiotics. We found high carriage rates of HMRGs in all genomes, with 100% carrying at least one copy of 11 out of 18 HMRGs. A total of 173 (56%) of the isolates carried both HMRGs and plasmid sequences. In the 25 genomes of antibiotic-resistant isolates, 80% (n = 20) carried HMRGs, ARGs, and plasmid sequences, while 40% (n = 10) had linked HMRGs and ARGs on their assembled genomes. We found no evidence of geographic variation in HMRG frequency, nor any association between locational proximity to Superfund sites and co-carriage of HMRGs and ARGs. Our study findings indicate that HMRGs are common among E. coli in marine ecosystems, suggesting widespread heavy metal presence in water sources of a region with history of environmental pollution. Further research is needed to determine the role HMRGs play in driving antimicrobial resistance in human pathogens through genetic linkage and the value their detection in environmental bacterial genomes may offer as an indicator of environmental heavy metal pollution.

Data-driven epidemiologic approach to conducting site feasibility for a global phase III tuberculosis vaccine clinical trial.

An efficacious tuberculosis (TB) vaccine is critical to reducing the global burden of TB. TB vaccine trials require the identification of multiple sites globally that have both a high incidence of TB and the capacity to conduct a clinical trial. To expand the diversity of potential phase III TB vaccine trial sites to be considered for inclusion, we describe a novel epidemiologic method that incorporates approaches from a variety of public health practices. Our approach incorporates analytic methodology to enable quantification and validation of qualitative information from disparate data sources, and epidemiologic analysis to systematically assess site-specific TB epidemiology. The integration of robust data-driven practices, and more quantitatively focused analysis, allowed for the objective evaluation of sites, which resulted in the identification of sites and catchment areas with high TB burden that may not have been previously considered. This suggests that an integrated epidemiologic methodology, not traditionally utilized for clinical trial site evaluations, could be integrated into site feasibility assessments as it results in more rapid site identification and reduces unintended bias.

Risk factors for developing both primary breast and primary ovarian cancer: A systematic review.

OBJECTIVE: Women with breast cancer have an increased risk of primary ovarian cancer (BR→OV), and women with ovarian cancer have an increased risk of primary breast cancer (OV→BR). This systematic review summarizes risk factors for developing BR→OV and OV→BR. METHODS: We searched PubMed and Embase until June 2022. RESULTS: We identified 23 articles meeting our inclusion criteria. Studies observed a lower risk of BR→OV for Black versus White women, alcohol consumption, radiotherapy and hormone therapy, BRCA2 versus BRCA1, and ER/PR positive versus negative breast tumors, and a higher risk with family history of breast/ovarian cancer, triple negative versus luminal breast cancer, and higher grade breast tumors. There was an increased risk of OV→BR with family history of cancer. CONCLUSIONS: Tumor characteristics, and genetic and familial factors are associated with risk of BR→OV and OV→BR. These results could aid clinicians in decision-making for breast and ovarian cancer patients, including risk-reducing strategies.

Frequency of HIV serodifferent couples within TB-affected households in a setting with a high burden of HIV-associated TB.

INTRODUCTION: Strong epidemiological links between human immunodeficiency virus (HIV) and tuberculosis (TB) may make household TB contact investigation an efficient strategy for HIV screening and finding individuals in serodifferent partnerships at risk of HIV and linking them to HIV prevention services. We aimed to compare the proportions of HIV serodifferent couples in TB-affected households and in the general population of Kampala, Uganda. METHODS: We included data from a cross-sectional trial of HIV counselling and testing (HCT) in the context of home-based TB evaluation in Kampala, Uganda in 2016-2017. After obtaining consent, community health workers visited the homes of participants with TB to screen contacts for TB and offer HCT to household members ≥ 15 years. We defined index participants and their spouses or parents as couples. Couples were classified as serodifferent if confirmed by self-reported HIV status or by HIV testing results. We used a two-sample test of proportions to compare the frequency of HIV serodifference among couples in the study to its prevalence among couples in Kampala in the 2011 Uganda AIDS Indicator Survey (UAIS). RESULTS: We included 323 index TB participants and 507 household contacts aged ≥ 18 years. Most index participants (55%) were male, while most (68%) adult contacts were female. There was ≥ 1 couple in 115/323 (35.6%) households, with most couples (98/115, 85.2%) including the index participant and spouse. The proportion of households with HIV-serodifferent couples was 18/323 (5.6%), giving a number-needed-to-screen of 18 households. The proportion of HIV serodifference among couples identified in the trial was significantly higher than among couples in the UAIS (15.7% vs. 8%, p = 0.039). The 18 serodifferent couples included 14 (77.8%) where the index participant was living with HIV and the spouse was HIV-negative, and 4 (22.2%) where the index partner was HIV-negative, while the spouse was living with HIV. CONCLUSIONS: The frequency of HIV serodifference among couples identified in TB-affected households was higher than in the general population. TB household contact investigation may be an efficient strategy for identifying people with substantial exposure to HIV and linking them to HIV prevention services.

SARS-CoV-2 antibody prevalence, correlates, and access to harm reduction services among people who inject drugs living with and without HIV and their partners in Kenya.

BACKGROUND: In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic. METHODS: This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting and/or sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence. RESULTS: One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range: 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] 0.51, 0.95; p < 0.01) Participants who reported a sexual or injecting partner diagnosed with SARS-CoV-2 were twofold more likely to have SARS-CoV-2 antibodies detected (aOR = 2.21, 95% CI 1.06, 4.58; p < 0.032). Living with HIV was not associated with presence of SARS-CoV-2 antibodies. CONCLUSION: The seroprevalence of SARS-CoV-2 of 30.9% in this cohort suggests high transmission rates within this population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV. A large portion of this population was noted to have had disruption in access to harm reduction services.

Association between health care access and food insecurity among lower-income older adults with multiple chronic conditions in Washington State, USA.

OBJECTIVE: Lower-income older adults with multiple chronic conditions (MCC) are highly vulnerable to food insecurity. However, few studies have considered how health care access is related to food insecurity among older adults with MCC. The aims of this study were to examine associations between MCC and food insecurity, and, among older adults with MCC, between health care access and food insecurity. DESIGN: Cross-sectional study data from the 2019 Behavioral Risk Factor Surveillance System survey. SETTING: Washington State, USA. PARTICIPANTS: Lower-income adults, aged 50 years or older (n 2118). MCC was defined as having ≥ 2 of 11 possible conditions. Health care access comprised three variables (unable to afford seeing the doctor, no health care coverage and not having a primary care provider (PCP)). Food insecurity was defined as buying food that did not last and not having money to get more. RESULTS: The overall prevalence of food insecurity was 26·0 % and was 1·50 times greater (95 % CI 1·16, 1·95) among participants with MCC compared to those without MCC. Among those with MCC (n 1580), inability to afford seeing a doctor was associated with food insecurity (prevalence ratio (PR) 1·83; 95 % CI 1·46, 2·28), but not having health insurance (PR 1·49; 95 % CI 0·98, 2·24) and not having a PCP (PR 1·10; 95 % CI 0·77, 1·57) were not. CONCLUSIONS: Inability to afford healthcare is related to food insecurity among older adults with MCC. Future work should focus on collecting longitudinal data that can clarify the temporal relationship between MCC and food insecurity.

Assisted Partner Services for People Who Inject Drugs: Index Characteristics Associated With Untreated HIV in Partners.

BACKGROUND: Assisted partner services (APSs) is a feasible, acceptable, and effective strategy that increases uptake of HIV testing; however, it has not been used widely among people who inject drugs (PWID) in Africa to notify sexual and injecting partners of potential exposures to HIV and provide testing services. SETTING: Nairobi, Kilifi, and Mombasa counties in Kenya. METHODS: PWID living with HIV (indexes) were enrolled and asked to provide contact information for sexual and injecting partners who were traced and offered HIV testing. APS efficiency was assessed by the number of indexes needed to interview (NNTI) to find 1 additional partner who was unaware of their HIV status or not on antiretroviral therapy (ART). We defined index participant characteristics associated with greater efficiency, defined as lower NNTIs. RESULTS: Among 783 indexes, the NNTI to identify one partner unaware of their HIV status was 7.1 and to identify one HIV-positive partner not on ART (regardless of status awareness) was 4.1. APS was provided to 977 partners and was more efficient in identifying partners who were not on ART (n = 201) among indexes who were female (NNTI = 2.9 vs. 5.7, P < 0.001), unaware of their HIV status (NNTI = 2.2 vs. 4.2, P = 0.009), not on ART (NNTI = 2.1 vs. 4.9; P < 0.001), not enrolled in a methadone program (NNTI = 3.3 vs. 10.4, P < 0.001), reported injecting <5 years (NNTI = 3.3 vs. 5.0; P = 0.005), or from Nairobi (NNTI = 3.2 vs. 5.6, P < 0.001). CONCLUSION: Scaling up APS among PWID living with HIV with certain characteristics could result in more efficient APS and greater partner engagement in HIV care.

Participation in methadone programs improves antiretroviral uptake and HIV viral suppression among people who inject drugs in Kenya.

BACKGROUND: HIV prevalence among people who inject drugs (PWID) in Kenya is estimated to be 18% compared to 4.5% in the general population. Studies from high-income countries have demonstrated that methadone use is associated with increased uptake of antiretroviral therapy (ART) and higher rates of viral suppression among PWID with HIV. However, it is unclear whether methadone use has the same effect among African PWID living with HIV. METHODS: We performed a cross-sectional study to evaluate associations between methadone program participation and ART uptake and viral suppression (HIV RNA viral load <1000 copies/ml) among PWID with HIV in Kenya. Participants were recruited from needle and syringe programs and methadone clinics, interviewed on site, and samples were obtained and assayed for HIV viral loads. Univariate and multiple logistic regression were used to determine associations. RESULTS: Among 679 participants, median age was 37 years, 48% were female, and 24% were in a methadone program. We observed higher proportions of ART use (96% vs. 87%, p = 0.001) and HIV viral suppression (78% vs. 65%, p = 0.012) among PWID on methadone compared to those not on methadone treatment. PWID who were not participating in a methadone program were 3-fold more likely to be off ART and approximately twice as likely to be viremic compared to those in methadone programs (adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI]: 1.35-8.35 and aOR = 1.90, 95% CI: 1.03-3.52, respectively). CONCLUSIONS: In this study, Kenyan PWID living with HIV participating in a methadone treatment program were more likely to be on ART and to have achieved viral suppression. Scale-up of methadone programs may have a positive impact on HIV epidemic control for this key population.

Significance of High-Containment Biological Laboratories Performing Work During the COVID-19 Pandemic: Biosafety Level-3 and -4 Labs.

High containment biological laboratories (HCBL) are required for work on Risk Group 3 and 4 agents across the spectrum of basic, applied, and translational research. These laboratories include biosafety level (BSL)-3, BSL-4, animal BSL (ABSL)-3, BSL-3-Ag (agriculture livestock), and ABSL-4 laboratories. While SARS-CoV-2 is classified as a Risk Group 3 biological agent, routine diagnostic can be handled at BSL-2. Scenarios involving virus culture, potential exposure to aerosols, divergent high transmissible variants, and zoonosis from laboratory animals require higher BSL-3 measures. Establishing HCBLs especially those at BSL-4 is costly and needs continual investments of resources and funding to sustain labor, equipment, infrastructure, certifications, and operational needs. There are now over 50 BSL-4 laboratories and numerous BSL-3 laboratories worldwide. Besides technical and funding challenges, there are biosecurity and dual-use risks, and local community issues to contend with in order to sustain operations. Here, we describe case histories for distinct HCBLs: representative national centers for diagnostic and reference, nonprofit organizations. Case histories describe capabilities and assess activities during COVID-19 and include capacities, gaps, successes, and summary of lessons learned for future practice.