Browsing by Author "Silverman, Rachel A."
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- Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, KenyaChung, Michael H.; Silverman, Rachel A.; Beck, Ingrid A.; Yatich, Nelly; Dross, Sandra; McKernan-Mullin, Jennifer; Bii, Stephen; Tapia, Kenneth; Stern, Joshua A.; Chohan, Bhavna; Sakr, Samah R.; Kiarie, James N.; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2016-06-19)Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.
- Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan womenMilne, Ross S.; Silverman, Rachel A.; Beck, Ingrid A.; McKernan-Mullin, Jennifer; Deng, Wenjie; Sibley, Thomas R.; Dross, Sandra; Kiarie, James N.; Sakr, Samah R.; Coombs, Robert W.; Chung, Michael H.; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2019-05-01)Objectives: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure. Design/Methods: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. Results: Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. Conclusion: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.
- A mixed methods investigation of how young adults in Virginia received, evaluated, and responded to COVID-19 public health messagingCook, Natalie E.; Wenzel, Sophie; Silverman, Rachel A.; Short, Danielle; Jiles, Kristina A.; Markwalter, Teresa; Friesen, Mary Ann (2022-09-22)The purpose of this study was to investigate how young adults in Virginia received, evaluated, and responded to messages related to the coronavirus/COVID-19, a major disruptor of our time, and to understand how and when these messages influenced behavior. This was a sequential explanatory mixed methods study, including an online survey (quantitative) and virtual focus groups (qualitative). We surveyed a convenience sample of 3,694 Virginia residents by distributing a link to complete the survey online. Only data from18-24 year old adults (n=207) were included in the analysis for this study. Focus group participants were recruited from the survey participants as well as from a college-level introductory health class. Most (83%) young adult respondents reported national science and health organizations as a trusted source for COVID-19 information and over 50% of respondents reported getting information from state/local health departments (72%), healthcare professionals (71%), and online news sources (51%). Focus group participants emphasized social media as an additional major source of COVID-19 information. Focus group data revealed that young adults struggled with deciphering contradictory messaging, had a mix of logical and emotional reasons for deciding whether to adhere to guidelines, had a desire for consistent, fact-based public health messaging at the national level. The findings from this study underscore the importance of consistent, positive public health messaging in a public health crisis.
- Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmissionKanthula, Ruth; Rossouw, Theresa M.; Feucht, Ute D.; van Dyk, Gisela; Beck, Ingrid A.; Silverman, Rachel A.; Olson, Scott; Salyer, Christen; Cassol, Sharon; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2017-05-15)Objectives: We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT). Design: A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa. Methods: Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013. HIV drug resistance testing was performed using the oligonucleotide ligation assay (OLA) on dried blood spots (DBS) collected at enrolment and monthly follow-up visits for 2 years. Results: South African children who failed HIV-prophylaxis had a high prevalence of NNRTI-resistant HIV (46/88; 52%). Among children with NNRTI-resistance, the frequency of the predominant resistant variant in each child's HIV-quasispecies was high (median 96%) at study entry (median age 7.5 months), and in 26 out of 27 followed a median of 13 months persisted at a high frequency (median 89%). Conclusion: Our finding that infants who fail HIV-prophylaxis frequently have long-lived NNRTI-resistant HIV suggests that resistance will likely persist through 36 months of age, when children qualify for NNRTI-based ART. These children may benefit from HIV drug resistance testing to guide selection of their treatment.
- Predictors of mortality within the first year of initiating antiretroviral therapy in urban and rural Kenya: A prospective cohort studySilverman, Rachel A.; John-Stewart, Grace C.; Beck, Ingrid A.; Milne, Ross S.; Kiptinness, Catherine; McGrath, Christine J.; Richardson, Barbra A.; Chohan, Bhavna; Sakr, Samah R.; Frenkel, Lisa M.; Chung, Michael H. (PLoS, 2019-10-04)Introduction Despite increased treatment availability, HIV-infected individuals continue to start antiretroviral therapy (ART) late in disease progression, increasing early mortality risk. Materials and methods Nested prospective cohort study within a randomized clinical trial of adult patients initiating ART at clinics in urban Nairobi and rural Maseno, Kenya, between 2013-2014. We estimated mortality incidence rates following ART initiation and used Cox proportional hazards regression to identify predictors of mortality within 12 months of ART initiation. Analyses were stratified by clinic site to examine differences in mortality correlates and risk by location. Results Among 811 participants initiated on ART, the mortality incidence rate within a year of initiating ART was 7.44 per 100 person-years (95% CI 5.71, 9.69). Among 207 Maseno and 612 Nairobi participants initiated on ART, the mortality incidence rates (per 100 person-years) were 12.78 (95% CI 8.49, 19.23) and 5.72 (95% CI 4.05, 8.09). Maseno had a 2.20-fold greater risk of mortality than Nairobi (95% CI 1.29, 3.76; P = 0.004). This association remained [adjusted hazard ratio (HR) = 2.09 (95% CI 1.17, 3.74); P = 0.013] when adjusting for age, gender, education, pre-treatment drug resistance (PDR), and CD4 count, but not when adjusting for BMI. In unadjusted analyses, other predictors (P<0.05) of mortality included male gender (HR = 1.74), age (HR = 1.04 for 1-year increase), fewer years of education (HR = 0.92 for 1-year increase), unemployment (HR = 1.89), low body mass index (BMI<18.5 m/kg2; HR = 4.99), CD4 count <100 (HR = 11.67) and 100-199 (HR = 3.40) vs. 200-350 cells/μL, and pre-treatment drug resistance (PDR; HR = 2.49). The increased mortality risk associated with older age, males, and greater education remained when adjusted for location, age, education and PDR, but not when adjusted for BMI and CD4 count. PDR remained associated with increased mortality risk when adjusted for location, age, gender, education, and BMI, but not when adjusted for CD4 count. CD4 and BMI associations with increased mortality risk persisted in multivariable analyses. Despite similar baseline CD4 counts across locations, mortality risk associated with low CD4 count, low BMI, and PDR was greater in Maseno than Nairobi in stratified analyses. Conclusions High short-term post-ART mortality was observed, partially due to low CD4 count and BMI at presentation, especially in the rural setting. Male gender, older age, and markers of lower socioeconomic status were also associated with greater mortality risk. Engaging patients earlier in HIV infection remains critical. PDR may influence short-term mortality and further studies to optimize management will be important in settings with increasing PDR.
- Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014Silverman, Rachel A.; Beck, Ingrid A.; Kiptinness, Catherine; Levine, Molly; Milne, Ross S.; McGrath, Christine J.; Bii, Steve; Richardson, Barbra A.; John-Stewart, Grace C.; Chohan, Bhavna; Sakr, Samah R.; Kiarie, James N.; Frenkel, Lisa M.; Chung, Michael H. (Oxford University Press, 2017-12-15)Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical trials registration: NCT01898754.
- Sexually Transmitted Disease Partner Services Costs, Other Resources, and Strategies Across Jurisdictions to Address Unique Epidemic Characteristics and Increased IncidenceSilverman, Rachel A.; Katz, David A.; Levin, Carol; Bell, Teal R.; Spellman, Dawn; St John, Lisa; Manley Rodriguez, Evelyn; Golden, Matthew R.; Barnabas, Ruanne V. (Wolters Kluwer Health, 2019-08)Background: Sexually transmitted disease (STD) partner services (PS) are a core component of STD programs. Data on costs are needed to support PS programming. Methods: In Washington State STD PS programs, disease intervention specialists (DIS) conduct telephone-based interviews and occasional field visits, offer expedited partner therapy to heterosexuals with gonorrhea or chlamydia, and promote human immunodeficiency virus (HIV) testing, preexposure prophylaxis, and HIV care. We conducted activity-based microcosting of PS, including: observational and self-reported time studies and interviews. We analyzed cost, surveillance, and service delivery data to determine costs per program outcomes. Results: In King, Pierce, and Spokane counties, respectively, DIS allocated 6.5, 6.4, and 28.8 hours per syphilis case and 1.5, 1.6, and 2.9 hours per gonorrhea/chlamydia case, on average. In 2016, each full-time DIS investigated 270, 268, and 61 syphilis and 1177, 1105, and 769 gonorrhea/chlamydia cases. Greater than 80% of syphilis cases in King and Pierce were among men who have sex with men versus 38% in Spokane. Disease intervention specialists spent 12% to 39% of their time actively interviewing cases and notifying partners (clients), and the remaining time locating clients, coordinating and verifying care, and managing case reports. Time spent on expedited partner therapy, HIV testing, and referrals to HIV treatment or preexposure prophylaxis, was minimal (<5 minutes per interview) at locations with resources outside PS staff. Program cost-per-interview ranged from US $527 to US $2210 for syphilis, US $219 to US $484 for gonorrhea, and US $164 to US $547 for chlamydia. Discussion: The STD PS resource needs depended on epidemic characteristics and program models. Integrating HIV prevention objectives minimally impacted PS-specific program costs. Results can inform program planning, future budget impact, and cost-effectiveness analyses.
- Vaccine Effectiveness During an Outbreak of COVID-19 Alpha Variant (B.1.1.7) in a Men’s Correctional Facility in Rural VirginiaSilverman, Rachel A.; Ceci, Alessandro; Cohen, Alasdair; Helmick, Meagan; Short, Erica; Bordwine, Paige; Friedlander, Michael J.; Finkielstein, Carla V. (2022-07)In April 2021, a COVID-19 outbreak occurred at a correctional facility in rural Virginia, USA. Eighty-four infections were identified among 854 incarcerated persons by facilitywide testing with reverse transcription quantitative PCR (qRT-PCR). We used whole-genome sequencing to link all infections to 2 employees infected with the B.1.1.7α (UK) variant. The relative risk comparing unvaccinated to fully vaccinated persons (mRNA-1273 [Moderna, https:// www.moderna.com]) was 7.8 (95% CI 4.8–12.7), corresponding to a vaccine effectiveness of 87.1% (95% CI 79.0%–92.1%). Average qRT-PCR cycle threshold values were lower, suggesting higher viral loads, among unvaccinated infected than vaccinated cases for the N, E, and S genes. Vaccination was highly effective at preventing SARS-CoV-2 infection in this high-risk setting. This approach can be applied to similar settings to estimate vaccine effectiveness as variants emerge to guide public health strategies during the ongoing pandemic.
- Vaccine Effectiveness during Outbreak of COVID-19 Alpha (B.1.1.7) Variant in Men’s Correctional Facility, United StatesSilverman, Rachel A.; Ceci, Alessandro; Cohen, Alasdair; Helmick, Meagan; Short, Erica; Bordwine, Paige; Friedlander, Michael J.; Finkielstein, Carla V. (Centers for Disease Control and Prevention, 2022-07)In April 2021, a COVID-19 outbreak occurred at a correctional facility in rural Virginia, USA. Eighty-four infections were identified among 854 incarcerated persons by facilitywide testing with reverse transcription quantitative PCR (qRT-PCR). We used whole-genome sequencing to link all infections to 2 employees infected with the B.1.1.7α (UK) variant. The relative risk comparing unvaccinated to fully vaccinated persons (mRNA-1273 [Moderna, https:// www.moderna.com]) was 7.8 (95% CI 4.8–12.7), corresponding to a vaccine effectiveness of 87.1% (95% CI 79.0%–92.1%). Average qRT-PCR cycle threshold values were lower, suggesting higher viral loads, among unvaccinated infected than vaccinated cases for the N, E, and S genes. Vaccination was highly effective at preventing SARS-CoV-2 infection in this high-risk setting. This approach can be applied to similar settings to estimate vaccine effectiveness as variants emerge to guide public health strategies during the ongoing pandemic.