RESUMO
BACKGROUND: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). METHODS: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up. DISCUSSION: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Análise Custo-Benefício , Aconselhamento , Feminino , Genótipo , Herpes Genital , Humanos , Lactente , Lesoto , Estudos Longitudinais , Masculino , Tanzânia , Falha de Tratamento , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT. METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed. FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study. INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART. FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation. TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.
Assuntos
Infecções por HIV , Viremia , Humanos , Infecções por HIV/tratamento farmacológico , Masculino , Feminino , Tanzânia/epidemiologia , Adolescente , Lesoto , Criança , Viremia/tratamento farmacológico , Pré-Escolar , Carga Viral , Lactente , Farmacorresistência Viral , Fármacos Anti-HIV/uso terapêutico , Adulto Jovem , Resultado do TratamentoRESUMO
BACKGROUND: Multi-month dispensing (MMD) of antiretroviral therapy (ART) represents one approach of differentiated service delivery (DSD) aiming to improve quality and cost-effectiveness for HIV services in resource-limited settings. However, reduction in clinic visits for people living with HIV (PLWH) should go along with out-of-clinic care tailored to PLWH`s preferences and comorbidities to maintain quality of care. eHealth supported MMD offers a potential solution. METHODS: Between October 2019 and January 2020 we assessed preferences on an eHealth supported MMD package among adult PLWH attending routine ART care at a rural clinic in Lesotho using a mixed-methods approach. Participants reported their preferences among different refill and eHealth options. They were invited to test automated text messages (SMS) informing about their viral load results, an automated tuberculosis symptoms screening call and telemedical support by an expert nurse. Telemedical service comprised a call-back option if participants required any additional support and adherence counselling for closer follow-up of participants with unsuppressed viral loads. After 6 weeks, participants were followed-up to assess perception of the chosen eHealth support using a qualitative approach. RESULTS: Among 112 participants (median age = 43 years; 74% female), 83/112 (75%) preferred MMD for 6-12 months (median = 9 months, IQR = [5, 12]). Neither sex, age, employment, costs and time for travel to clinic, nor the duration of taking ART correlated with the MMD preference. All 17 participants attending routine viral load measurement wished to receive the result via SMS. Fifteen (19.2%) participants requested a telemedical nurse call-back during the study period. All participants with recent unsuppressed viral load (N = 13) requested telemedical adherence counselling for closer follow-up. Among 78 participants followed-up, 76 (97%) would appreciate having the call-back option in future. Seventy-five participants (67%) received and evaluated the automated symptomatic tuberculosis screening call, overall 71 (95%) appreciated it. CONCLUSIONS: The great majority of PLWH in this study preferred 6-12 months MMD and appreciated the additional eHealth support, including viral load results via SMS, telemedical nurse consultations and automated tuberculosis symptom screening calls. eHealth supported MMD packages appear to be a promising approach for DSD models and should be assessed for clinical endpoints and cost-effectiveness in larger studies.