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      Antiretroviral drug switches to zidovudine‐based regimens and loss to follow‐up during the first COVID‐19 lockdown in Bali, Indonesia

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          Abstract

          Objectives

          International lockdowns during the COVID‐19 pandemic impacted antiretroviral drug supplies in Indonesia. We assessed the impact of antiretroviral treatment (ART) provision and being lost to follow‐up (LTFU) on people living with HIV, attending a key population‐focused HIV clinic in Denpasar, Bali.

          Methods

          This was a retrospective note review of anonymized data from adult Indonesian patients living with HIV. We collected demographic data and information on being LTFU, and assessed the numbers of patients impacted by ART switches from fixed‐dose combination (FDC) tenofovir/lamivudine/efavirenz to multi‐pill zidovudine‐based regimens, during the first international lockdown from March 2020.

          Results

          Records of 260 Indonesian adult patients registered for HIV care and prescribed ART were reviewed; 240 (92.3%) were men, and 90% were men who have sex with men. Between 13 March and 28 May 2020, 214 (87%) out of 247 patients (previously diagnosed with HIV) had to switch to individual, multi‐pill zidovudine‐based regimens from their FDC. The switch lasted a mean of 35 days (range 10–85). Twenty‐five patients (10%) were LTFU; patients who switched were more likely to remain in care. Data on viral load status and toxicity are lacking as laboratory testing requires self‐payment.

          Conclusions

          The majority of patients living with HIV had no choice but to switch to multi‐pill, zidovudine‐based regimens.

          Despite significant efforts to minimize the impact of lockdown on care, 10% of patients were LTFU. Patients switching ART required greater clinic attention and support, improving retention.

          Complete national data are needed to understand the impact of ART stockouts on virological suppression and drug resistance throughout Indonesia.

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          Most cited references9

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          Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

          (2016)
          Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count <100 cells per μL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1·48, 95% CI 1·20–1·82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0·626]). Interpretation We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. Funding The Wellcome Trust.
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            The cascade of HIV care among key populations in Indonesia: a prospective cohort study

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              Evolving ART crisis for people living with HIV in Indonesia

              Country lockdowns in response to the COVID-19 pandemic are causing drug shortages that are crippling health-care provision for people living with HIV in Indonesia. The supply chain of antiretroviral treatment (ART) has halted amid lockdowns and travel restrictions from India. 1 Many Indonesian districts have completely run out of ART, with other districts running out within 2 weeks. This shortage will result in tens of thousands of people living with HIV stopping ART treatment. All ART procurement and administration is handled via the Indonesian Ministry of Health, but drugs are procured from outside the country. First-line ART predominantly involves generic fixed-dosed tenofovir, lamivudine, and efavirenz via Mylan (Canonsburg, PA, USA); some supplies are stuck in procurement systems with no further supplies able to come in. Our clinic, a key population HIV/sexual health clinic in Bali, has made provisions to ration tenofovir, lamivudine, and efavirenz to 10 days' supply at once and made switches to zidovudine-based treatment; we have also stopped immediate ART start. At present, all our stocks of drugs will run out within 2 weeks. There has been disconnected local advice to supply patients with mono or dual ART using existing low stocks of nucleoside reverse transcriptase inhibitors (lamivudine and zidovudine) and non-nucleoside reverse transcriptase inhibitors (efavirenz or nevirapine) to keep people going, which would have terrible consequences in driving ART drug resistance. We have restricted, controlled supply of boosted lopinavir reserved for second-line and third-line treatment. Many of our patients, who are mostly men who have sex with men, live far away but prefer to visit our service rather than government general community clinics, where greater levels of stigma might exist. Many of our patients have lost jobs because of the COVID-19 crisis, have moved back home to different islands, and will stop ART. High loss to follow-up and poor ART adherence already exist, as reflected in poor UNAIDS HIV testing and treatment outcomes. 2 Such outcomes increase the vulnerability of these individuals to infections and ill health, potentially including COVID-19, when they are off ART and accelerate the existing fast-growing HIV epidemic. The Indonesian Ministry of Health has recommended an operational programme for special populations, including people with HIV, and a sped up agreement to supply a maximum of 2–3 months ART (normally 1 month) if drugs are available in high-burden HIV districts and epicentres of the COVID-19 outbreak. These challenges have been brought to the attention of the Presidential Office in Indonesia and the Global Fund to Fight AIDS, Tuberculosis and Malaria, who are aiming to purchase and prioritise the procurement of a small number of tenofovir-based regimens from India via specially arranged shipping, which are expected to arrive in late April. Unfortunately, this will not be enough for the shortages throughout the country.
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                Author and article information

                Contributors
                keertigedela@gmail.com
                Journal
                HIV Med
                HIV Med
                10.1111/(ISSN)1468-1293
                HIV
                HIV Medicine
                John Wiley and Sons Inc. (Hoboken )
                1464-2662
                1468-1293
                21 March 2022
                21 March 2022
                : 10.1111/hiv.13298
                Affiliations
                [ 1 ] Chelsea & Westminster NHS Foundation Trust London UK
                [ 2 ] Yayasan Bali Peduli HIV/Sexual Health Clinic Denpasar Indonesia
                [ 3 ] Pusat Unggulan Kebijakan Kesehatan dan Inovasi Sosial (PUI‐PT PPH, PUK21S) HIV/AIDS Research Centre Atma Jaya Catholic University Jakarta Indonesia
                Author notes
                [*] [* ] Correspondence

                Keerti Gedela, Chelsea & Westminster NHS Foundation Trust, London, UK.

                Email: keertigedela@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-5797-8216
                https://orcid.org/0000-0001-5082-8656
                Article
                HIV13298
                10.1111/hiv.13298
                9111556
                35312145
                251b371b-154b-4b29-9b14-a136e4870a9a
                © 2022 British HIV Association

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 28 February 2022
                : 15 February 2022
                : 01 March 2022
                Page count
                Figures: 0, Tables: 1, Pages: 6, Words: 3476
                Funding
                Funded by: Medical Research Council , doi 10.13039/501100007155;
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.6 mode:remove_FC converted:17.05.2022

                Infectious disease & Microbiology
                antiretroviral treatment,covid‐19,hiv,indonesia,lockdown
                Infectious disease & Microbiology
                antiretroviral treatment, covid‐19, hiv, indonesia, lockdown

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