Need assessment for HIV drug resistance testing and landscape of current and future technologies in low- and middle-income countries

Parkin, Neil; Harrigan, P. Richard; Inzaule, Seth; Bertagnolio, Silvia

doi:10.1371/journal.pgph.0001948

Cited by 5 publications

(2 citation statements)

References 54 publications

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“… 37 As a result, there are no established standards in the literature for such estimations at the country level or within smaller geographic areas. 38 It is necessary to use estimated proportion of receiving DRT among people living with HIV to approximate the DRT demand.…”

Section: Methodsmentioning

confidence: 99%

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

Wang,

Kingwara,

Wagner

et al. 2024

BMJ Open

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BackgroundHIV drug resistance (DR) is a growing threat to the durability of current and future HIV treatment success. DR testing (DRT) technologies are very expensive and specialised, relying on centralised laboratories in most low and middle-income countries. Modelling for laboratory network with point-of-care (POC) DRT assays to minimise turnaround time (TAT), is urgently needed to meet the growing demand.MethodsWe developed a model with user-friendly interface using integer programming and queueing theory to improve the DRT system in Kisumu County, Kenya. We estimated DRT demand based on both current and idealised scenarios and evaluated a centralised laboratory-only network and an optimised POC DRT network. A one-way sensitivity analysis of key user inputs was conducted.ResultsIn a centralised laboratory-only network, the mean TAT ranged from 8.52 to 8.55 working days, and the system could not handle a demand proportion exceeding 1.6%. In contrast, the mean TAT for POC DRT network ranged from 1.13 to 2.11 working days, with demand proportion up to 4.8%. Sensitivity analyses showed that expanding DRT hubs reduces mean TAT substantially while increasing the processing rate at national labs had minimal effect. For instance, doubling the current service rate at national labs reduced the mean TAT by only 0.0%–1.9% in various tested scenarios, whereas doubling the current service rate at DRT hubs reduced the mean TAT by 37.5%–49.8%. In addition, faster batching modes and transportation were important factors influencing the mean TAT.ConclusionsOur model offers decision-makers an informed framework for improving the DRT system using POC in Kenya. POC DRT networks substantially reduce mean TAT and can handle a higher demand proportion than a centralised laboratory-only network, especially for children and pregnant women living with HIV, where there is an immediate push to use DRT results for patient case management.

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Section: Methodsmentioning

confidence: 99%

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

Wang,

Kingwara,

Wagner

et al. 2024

BMJ Open

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“…HIV-1 has been shown to adapt in response to host immune, antiretroviral, and vaccine pressure ( 11 – 14 ). The rapid development of drug resistance mutations that was observed when monotherapies became available in the 1990s has been mitigated by the use of a combination of antiretrovirals, although drug resistance mutations have increased in some populations ( 15 ). For T cell immune responses, the observation of T cell escape mutations at the individual level ( 12 ) was followed by evidence of HIV-1 adaptation at the population level with HLA-associated polymorphisms spreading in populations where a given HLA is more frequent ( 16 – 18 ), leading to partially predictable HIV-1 escape pathways ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s

Lewitus,

Li,

Bai

et al. 2024

mBio

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Global surveillance of HIV-1 sequences is critical for designing relevant prophylactic and therapeutic interventions to infection. We designed an open-source platform, Hervé, for analyzing and visualizing the diversification dynamics of HIV-1 protein sequences. We characterized the evolution of over 12,000 HIV-1 Env, Gag, and Pol protein sequences from 1980–2020 and found that, despite a steady increase in intra-subtype and circulating recombinant form diversity, the most frequent residue at each site, i.e., the consensus, has varied only moderately.

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Challenges for Novel Antiretroviral Development in an Era of Widespread tenofovir-disoproxil/lamivudine (or emtricitabine)/dolutegravir availability (TLD) Availability

Fairhead,

Levi,

Hill

2024

Clinical Infectious Diseases

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Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.

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Need assessment for HIV drug resistance testing and landscape of current and future technologies in low- and middle-income countries

Cited by 5 publications

References 54 publications

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s

Challenges for Novel Antiretroviral Development in an Era of Widespread tenofovir-disoproxil/lamivudine (or emtricitabine)/dolutegravir availability (TLD) Availability

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