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1.
Clin Infect Dis ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657086

RESUMO

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

2.
BMC Health Serv Res ; 24(1): 792, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982430

RESUMO

BACKGROUND: Recently-updated global guidelines for cervical cancer screening incorporated new technologies-most significantly, the inclusion of HPV DNA detection as a primary screening test-but leave many implementation decisions at countries' discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. METHODS: Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing "triage" approaches-i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. RESULTS: Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. CONCLUSIONS: These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias do Colo do Útero , Humanos , Feminino , Malaui/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/economia , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Adulto , Pessoa de Meia-Idade , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Crioterapia/economia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos
3.
J Acquir Immune Defic Syndr ; 95(1): 42-51, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37757844

RESUMO

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV incidence in pregnant and breastfeeding women, but adherence is essential. METHODS: We conducted a pilot randomized trial to evaluate an intervention package to enhance antenatal and postnatal PrEP use in Lilongwe, Malawi. The intervention was based on patient-centered counseling adapted from previous PrEP studies, with the option of a participant-selected adherence supporter. Participants were locally eligible for PrEP and randomized 1:1 to intervention or standard counseling (ie, control) and followed for 6 months. Participants received the intervention package or standard counseling at enrollment, 1, 3, and 6 months. Adherence was measured through plasma and intracellular tenofovir concentrations and scored using a published algorithm. Our primary outcome was retention in care with concentrations consistent with 4-7 doses/week. RESULTS: From June to November 2020, we enrolled 200 pregnant women with the median gestational age of 26 (interquartile range: 19-33) weeks. Study retention was high at 3 months (89.5%) and 6 months (85.5%). By contrast, across the 2 time points, 32.8% of participants retained in the study had adherence scores consistent with 2-5 doses/week while 10.3% had scores consistent with daily dosing. For the composite primary end point, no substantial differences were observed between the intervention and control groups at 3 months (28.3% vs. 29.0%, probability difference: -0.7%, 95% confidence interval: -13.3%, 11.8%) or at 6 months (22.0% vs. 26.3%, probability difference: -4.3%, 95% confidence interval: -16.1%, 7.6%). CONCLUSIONS: In this randomized trial of PrEP adherence support, retention was high, but less than one-third of participants had pharmacologically confirmed adherence of ≥4 doses/week. Future research should focus on antenatal and postnatal HIV prevention needs and their alignment across the PrEP continuum, including uptake, persistence, and adherence.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Feminino , Gravidez , Lactente , Infecções por HIV/tratamento farmacológico , Projetos Piloto , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Malaui , Adesão à Medicação , Assistência Centrada no Paciente
4.
Res Sq ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38196656

RESUMO

Background: New or returning ART clients are often ineligible for differentiated service delivery (DSD) models, though they are at increased risk of treatment interruption and may benefit greatly from flexible care models. Stakeholder support may limit progress on development and scale-up of interventions for this population. We qualitatively explored stakeholder perceptions of and decision-making criteria regarding DSD models for new or returning ART clients in Malawi. Methods: We conducted in-depth interviews with internationally based stakeholders (from foundations, multilateral organizations, and NGOs) and Malawi-based stakeholders (from the Malawi Ministry of Health and PEPFAR implementing partners). The interviews included two think-aloud scenarios in which participants rated and described their perceptions of 1) the relative importance of five criteria (cost, effectiveness, acceptability, feasibility, and equity) in determining which interventions to implement for new or returning ART clients and 2) their relative interest in seven potential interventions (monetary incentives, nonmonetary incentives, community-based care, ongoing peer/mentor support and counseling, eHealth, facility-based interventions, and multimonth dispensing) for the same population. The interviews were completed in English via video conference and were audio-recorded. Transcriptions were coded using ATLAS.ti version 9. We examined the data using thematic content analysis and explored differences between international and national stakeholders. Results: We interviewed twenty-two stakeholders between October 2021 and March 2022. Thirteen were based internationally, and nine were based in Malawi. Both groups prioritized client acceptability but diverged on other criteria: international stakeholders prioritized effectiveness, and Malawi-based stakeholders prioritized cost, feasibility, and sustainability. Both stakeholder groups were most interested in facility-based DSD models, such as multimonth dispensing and extended facility hours. Nearly all the stakeholders described person-centered care as a critical focus for any DSD model implemented. Conclusions: National and international stakeholders support DSD models for new or returning ART clients. Client acceptability and long-term sustainability should be prioritized to address the concerns of nationally based stakeholders. Future studies should explore the reasons for differences in national and international stakeholders' priorities and how to ensure that local perspectives are incorporated into funding and programmatic decisions.

5.
Viruses ; 16(1)2023 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-38257730

RESUMO

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.


Assuntos
Infecções por HIV , HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Humanos , Malaui/epidemiologia , Resultado do Tratamento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Integrases
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