Browsing by Author "Bolton Moore C"

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A controlled study to assess the effects of a Fast Track (FT) service delivery model among stable HIV patients in Lusaka Zambia.
(2022) Bolton Moore C; Pry JM; Mukumbwa-Mwenechanya M; Eshun-Wilson I; Topp S; Mwamba C; Roy M; Sohn H; Dowdy DW; Padian N; Holmes CB; Geng EH; Sikazwe I
Fast Track models-in which patients coming to facility to pick up medications minimize waiting times through foregoing clinical review and collecting pre-packaged medications-present a potential strategy to reduce the burden of treatment. We examine effects of a Fast Track model (FT) in a real-world clinical HIV treatment program on retention to care comparing two clinics initiating FT care to five similar (in size and health care level), standard of care clinics in Zambia. Within each clinic, we selected a systematic sample of patients meeting FT eligibility to follow prospectively for retention using both electronic medical records as well as targeted chart review. We used a variety of methods including Kaplan Meier (KM) stratified by FT, to compare time to first late pick up, exploring late thresholds at >7, >14 and >28 days, Cox proportional hazards to describe associations between FT and late pick up, and linear mixed effects regression to assess the association of FT with medication possession ratio. A total of 905 participants were enrolled with a median age of 40 years (interquartile range [IQR]: 34-46 years), 67.1% were female, median CD4 count was 499 cells/mm3 (IQR: 354-691), and median time on ART was 5 years (IQR: 3-7). During the one-year follow-up period FT participants had a significantly reduced cumulative incidence of being >7 days late for ART pick-up (0.36, 95% confidence interval [CI]: 0.31-0.41) compared to control participants (0.66; 95% CI: 0.57-0.65). This trend held for >28 days late for ART pick-up appointments, at 23% (95% CI: 18%-28%) among intervention participants and 54% (95% CI: 47%-61%) among control participants. FT models significantly improved timely ART pick up among study participants. The apparent synergistic relationship between refill time and other elements of the FT suggest that FT may enhance the effects of extending visit spacing/multi-month scripting alone. ClinicalTrials.gov Identifier: NCT02776254 https://clinicaltrials.gov/ct2/show/NCT02776254.
Cervical cancer screening outcomes in Zambia, 2010-19: a cohort study.
(2021-Jun) Pry JM; Manasyan A; Kapambwe S; Taghavi K; Duran-Frigola M; Mwanahamuntu M; Sikazwe I; Matambo J; Mubita J; Lishimpi K; Malama K; Bolton Moore C
BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort. METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level. FINDINGS: Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 [77·8%]). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14-6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2-22·9) of screening positive. INTERPRETATION: CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets. FUNDING: US President's Emergency Plan for AIDS Relief.
Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.
(2022) Pry JM; Vinikoor MJ; Bolton Moore C; Roy M; Mody A; Sikazwe I; Sharma A; Chihota B; Duran-Frigola M; Daultrey H; Mutale J; Kerkhoff AD; Geng EH; Pollock BH; Vera JH
As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR <60ml/min/1.73m2 allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28-40), and median CD4 cell count was 292 (IQR: 162-435). The proportion of individuals with an eGFR <60ml/min/1.73m2 was 6.9% (95% CI: 6.7-7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2 p-value <0.001). Estimated GFR less than 60ml/min/1.73m2, per the unadjusted CKD-EPI equation, was significantly associated with age, sex, body mass index, and blood pressure. Using routine serum creatinine measures, we identified a significant proportion of individuals with eGFR indicating moderate or great kidney function impairment among PLHIV initiating ART in Zambia. It is possible that differentiated service delivery models could be developed to address this subset of those in HIV care with increased risk of chronic kidney disease.
'I need time to start antiretroviral therapy': understanding reasons for delayed ART initiation among people diagnosed with HIV in Lusaka, Zambia'.
(2022-Dec) Mwamba C; Beres LK; Topp SM; Mukamba N; Simbeza S; Sikombe K; Mody A; Geng E; Holmes CB; Kennedy CE; Sikazwe I; Denison JA; Bolton Moore C
INTRODUCTION: Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately. METHODS: We conducted a qualitative study to inform interventions supporting rapid initiation in the 'Test and Start' era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation. RESULTS: Drawing on messages gleaned from facility-based counselling and community information, many cited greater fear of rapid sickness or death due to imperfect adherence or treatment side effects than negative health consequences due to delayed initiation. Participants described needing time to 'prepare' their minds for a lifetime treatment commitment. Concerns about inadvertent HIV status disclosure during drug collection discouraged immediate initiation, as did feeling healthy, and worries about the impact of ART initiation on relationship dynamics. CONCLUSION: Findings suggest that counselling messages should accurately communicate treatment risks, without perpetuating fear-based narratives about HIV. Identifying and managing patient-specific concerns and reasons for the 'need for time' may be important for supporting individuals to rapidly accept lifelong treatment.Key messagesFear-based adherence messaging in health facilities about the dangers of missing a treatment dose or changing the time when ART is taken contributes to Zambian patients' refusals of immediate ART initiationResponsive health systems that balance a stated need for time to accept one's diagnosis and prepare to embark on a lifelong treatment plan with interventions to identify and manage patient-specific treatment related fears and concerns may support more rapid ART initiationPerceived social stigma around HIV continues to be a significant challenge for treatment initiation.
Impact of CYP2B6 genotype, tuberculosis therapy, and formulation on efavirenz pharmacokinetics in infants and children under 40 months of age.
(2022-Mar-15) Nikanjam M; Tran L; Chadwick EG; Bwakura-Dangarembizi M; Bolton Moore C; Samson P; Spector SA; Chakhtoura N; Jean-Philippe P; Frenkel L; Zimmer B; Benns A; Libous J; Capparelli EV
OBJECTIVE: Dosing efavirenz (EFV) in children less than 3 years of age is challenging due to large variability in drug levels. This study evaluated differences in pharmacokinetics with tuberculosis (TB) therapy, formulation, age, and CYP2B6 genotype. DESIGN: Pharmacokinetic data from three IMPAACT/PACTG studies (P382, P1021, and P1070) for children initiating therapy less than 40 months of age were evaluated. METHODS: Pharmacokinetic data were combined in a population pharmacokinetic model. Exposure from the 2-week pharmacokinetic visit was compared with changes in viral RNA between the Week 0 and Week 4 visits. RESULTS: The model included 103 participants (19 on TB therapy). CYP2B6 516 genotype information was available for 82 participants (TT: 15, GT: 28, GG: 39). Median age at the first pharmacokinetic visit was 17.0 months (range: 2.0-39.0 months). Liquid formulation led to a 42% decrease in bioavailability compared with opened capsules. TB therapy (isoniazid and rifampin) led to a 29% decreased clearance, however Monte Carlo simulations demonstrated the majority of participants on TB therapy receiving standard EFV dosing to be in the target area under the curve range. Clearance was 5.3-fold higher for GG than TT genotype and 3.3-fold higher for GT than TT genotype. Age did not have a significant effect on clearance in the final model. Initial viral RNA decay was lower for patients in the lowest quartile of exposures (area under the curves) than for higher quartiles (P = 0.013). CONCLUSION: EFV dosing should account for CYP2B6 516 genotype and formulation, but does not require adjustment for concurrent TB therapy.
Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regression.
(2022-Jan) Pry JM; Sikombe K; Mody A; Iyer S; Mutale J; Vlahakis N; Savory T; Wa Mwanza M; Mweebo K; Mwila A; Mwale C; Mukumbwa-Mwenechanya M; Kerkhoff AD; Sikazwe I; Bolton Moore C; Mwamba D; Geng EH; Herce ME
INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.
Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.
(2024-Apr) Gaur AH; Capparelli EV; Calabrese K; Baltrusaitis K; Marzinke MA; McCoig C; Van Solingen-Ristea RM; Mathiba SR; Adeyeye A; Moye JH; Heckman B; Lowenthal ED; Ward S; Milligan R; Samson P; Best BM; Harrington CM; Ford SL; Huang J; Crauwels H; Vandermeulen K; Agwu AL; Smith-Anderson C; Camacho-Gonzalez A; Ounchanum P; Kneebone JL; Townley E; Bolton Moore C
BACKGROUND: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. METHODS: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC INTERPRETATION: Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. FUNDING: The National Institutes of Health and ViiV Healthcare.