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20 Jul 2017

#HIV #drug #resistance #report 2017 (@WHO, Jul 20 ‘17, summary)


Title: #HIV #drug #resistance #report 2017.

Subject: HIV/AIDS, antiviral drugs resistance, current situation.

Source: World Health Organization (WHO), full PDF file: (LINK). Summary.

Code: [     ]

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HIV drug resistance report 2017

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ISBN 978-92-4-151283-1

© World Health Organization 2017 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization.

Suggested citation. HIV drug resistance report 2017. Geneva: World Health Organization; 2017.

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Executive Summary

  • Antimicrobial resistance (AMR) is a growing global public health threat, which urgently requires collective action to ensure effective prevention and treatment of infections. Minimizing the emergence and transmission of HIV drug resistance (HIVDR) is a critical aspect of the broader global response to AMR. Prevention, monitoring and response to HIVDR is key to building and sustaining gains in HIV treatment scale-up, and achieving the global 90-90-90 targets for treatment. These widely adopted targets reflect the global community’s commitment to expanding access to antiretroviral therapy (ART) including: diagnosing 90% of all people with HIV infection; providing treatment to 90% of those diagnosed; and ensuring 90% of people on treatment achieve virological suppression, by 2020. By the end of 2016, 70% of people living with HIV (PLHIV) were diagnosed,77% of those who knew their HIV status received ART, and 82% of those on treatment were virally suppressed.
  • The human cost of HIVDR cannot be underestimated: people with non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance are less likely to achieve viral suppression; more likely to experience virological failure or death; more likely to discontinue treatment; and more likely to acquire new HIVDR mutations. Preventing, monitoring and responding to HIVDR is therefore critical to maintaining current achievements, improving treatment outcomes for PLHIV, protecting investments, and guaranteeing the long-term sustainability of care and treatment programmes. Mathematical modelling predicts that if NNRTIs continue to be included in first-line ART regimens, and the level of pretreatment HIV drug resistance (PDR) to NNRTIs reaches above 10% in subSaharan Africa, the global targets to end AIDS as a public health threat by 2030 will not be attained. Achieving and sustaining “the last 90” target will therefore require efforts to contain and respond to HIVDR.
  • Recognizing the importance of addressing HIVDR, within the context of ART scale-up, the World Health Organization (WHO), in collaboration with partners, developed a comprehensive HIVDR surveillance approach in 2004, with guidance updated in 2014 to yield nationally representative estimates of HIVDR.
  • This second HIVDR report has been jointly developed by WHO, the United States Centers for Disease Control and Prevention (US-CDC) and the Global Fund to Fight AIDS, Tuberculosis and Malaria (“The Global Fund”). It provides an update on recent population levels of HIVDR covering the period 2014–2016. The report includes data from 16 nationally representative surveys from 14 countries1 estimating resistance in: adults initiating ART (PDR), children younger than 18 months newly diagnosed with HIV, and adults on ART (acquired HIV drug resistance or ADR). To contextualize results from representative HIVDR surveys, the report is supported by systematic reviews of the published literature on PDR in adults, children and adolescents, and ADR in paediatric and adult populations. Finally, the report includes the prevalence of transmitted HIV drug resistance (TDR) in recently infected people in Malawi and Zimbabwe, estimated as part of recent household Population-based HIV Impact Assessment (PHIA) surveys, supported by the United States President’s Emergency Plan for AIDS Relief (PEPFAR).
  • Twenty-six countries have completed or are currently implementing national HIVDR surveys, based on WHO’s guidance. The swift uptake and implementation of HIVDR surveillance in recent years reflects the commitment of countries, partners and donors to AMR and the monitoring of HIVDR as part of ART scale-up efforts.
  • Of the 26 countries with national HIVDR surveys that are completed or ongoing, 14 have reported data to WHO, and are captured in this report. Brisk uptake of WHO’s revised HIVDR surveillance methods since their publication in 2014 reflects the collective efforts and commitment of countries, and pivotal support provided by US-CDC, the Global Fund, WHO and other partners.
  • Levels of pretreatment resistance to efavirenz or nevirapine, the most affordable and widely used drugs in first-line ART, reached 10% or above in six out of 11 countries that reported PDR survey data.
  • Nationally representative surveys of PDR monitor resistance in people starting ART, including antiretroviral (ARV) drug-naive individuals and people reporting prior exposure to ARV drugs. Levels of NNRTI resistance (defined as resistance to efavirenz or nevirapine) were high (>10%) in six of the 11 countries reporting data (see figure below).
  • Three out of the five countries with NNRTI resistance below 10% monitored PDR only in ARV drug-naive individuals, which may explain the lower prevalence estimates observed in these countries. In the African Region, levels of NNRTI resistance were greater than 10% in three out of four countries, with NNRTI PDR ranging from 8.1% (95% CI 4.3–14.7) in Cameroon to 15.4% (95% CI 10.3–22.5) in Uganda. In Mexico, Central and South America, pretreatment NNRTI resistance exceeded 10% in three of six surveys, ranging from 6.3% (95% CI 3.8-10.2) in Colombia to 19.3% (95% CI 12.2–29.1) in Nicaragua. Finally, in Myanmar, the only country reporting PDR survey data from South-East Asia, NNRTI resistance was low at 3.9% (95% CI 2.1–7.4). Overall, the prevalence of NNRTI resistance reported in PDR surveys is broadly consistent with available data from the PHIA surveys among recently infected people in Malawi and Zimbabwe, where four out of 26 and two out of 30 ARV drug-naive individuals had NNRTI resistance, respectively.
  • Survey findings are also consistent with a systematic review of studies published between 2001 and 2016, which assessed levels of PDR in 56 044 adults across 63 low- and middle-income countries. NNRTI resistance was higher in more recent studies across all regions (Eastern Africa, Southern Africa, Western and Central Africa, Latin America and Asia; P<0.05 for all). Yearly incremental increases in NNRTI resistance were greatest for studies in Eastern Africa (29%, 95% CI 17–42) and smallest for those in Asia (11%, 95% CI 2–20).
  • Pretreatment drug resistance is more than two fold higher among people starting first-line ART with prior ARV drug exposure, compared to ARV drug-naive individuals. With continued ART scale-up, this group is likely to represent an increasing proportion of people initiating treatment who may not be receiving effective treatment.
  • Notably, individuals with prior ARV drug exposure initiating or reinitiating first-line ART had higher prevalence of NNRTI PDR in both PDR surveys and the systematic review. Across the seven PDR surveys that included both individuals with prior ARV exposure – previously on first-line ART or past exposure for prevention of mother-to-child transmission (PMTCT) – and ARV drug-naive individuals, NNRTI resistance was considerably higher among ART initiators with prior ARV drug exposure (21.6%, 95% CI 13.8–32.2), compared to ARV drug-naive treatment initiators (8.3%, 95% CI 6.0–11.4; P<0.0001). The high levels of NNRTI resistance in people reporting prior ARV drug exposure is particularly concerning, as this group is likely to represent an ever-increasing proportion of first-line treatment initiators in some countries. Recognizing that levels of NNRTI resistance are increasing, and that NNRTIs are an essential component of currently recommended first-line ART, WHO has published Guidelines on
    the public health response to pretreatment HIV drug resistance, as a supplement to the 2016 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. These guidelines include new recommendations on the selection of ARV drugs in response to high levels of PDR. They recommend countries consider changing their first-line ART regimen if levels of NNRTI PDR reach 10%. These publications are an important step forward in the global response to HIVDR.
  • Most available PDR data come from adult populations, while data for children and adolescents are limited. Only one nationally representative HIVDR survey among children younger than 18 months was reported between 2014 and 2016; this survey was from South Africa, and documented NNRTI prevalence as high as 63.7% (95% CI 59.0–68.4) in infants diagnosed with HIV through early infant diagnosis. The high levels of NNRTI resistance observed in this survey and in other recent publications strongly support WHO’s 2013 recommendation that all children younger than 3 years of age be started on protease inhibitor (PI)-based regimens, irrespective of PMTCT exposure. Unfortunately, implementation of this policy has been slow, largely due to the unavailability, until recently, of heat stable and palatable paediatric formulations, which do not require a cold chain until the point of dispensing.
  • The global target of 90% virological suppression in people retained on ART was reached in two of the four countries that reported survey data. Among the four countries, it ranged from 68% to 90%, indicating variability in programme quality and service delivery that should be addressed.
  • Achieving optimal viral load suppression and minimizing HIVDR is critical to reaching the 90-90-90 fast track targets by 2020 and eliminating AIDS as a public health threat by 2030. Between 2014 and 2016, four countries (Cameroon, Guatemala, Viet Nam and Zambia) implemented ADR surveys among adults on ART and reported data to WHO. Only Zambia and Viet Nam reached the 90% target for viral load suppression. The heterogeneity in the viral load suppression rates reported among people on ART suggest substantial differences in programme performance across countries.
  • NNRTI resistance among people retained on ART ranged from 4% to 28%, while among people with unsuppressed viral load on first-line NNRTI regimens, it ranged from 47% to 90%. This speaks to the need to scale up viral load testing, promptly switch individuals with confirmed virological failure to second-line treatment, and strengthen adherence support in countries with lower levels of ADR.
  • Overall, the prevalence of NNRTI resistance among individuals on ART for 12–24 months ranged from 4.3% (95% CI 1.9–9.5) in Zambia to 16.7.% (95% CI 13.7–20.2) in Cameroon; among those on treatment for longer durations (36–48+ months), it ranged from 4.2% (95% CI 2.4–7.4) in Viet Nam to 28.3% in Cameroon (95% CI 17.4–42.5). Among people on first-line NNRTI-based regimens with unsuppressed viral load, the prevalence of NNRTI resistance at the 12–24 month time point ranged from 47.3% (95% CI 10.7–87.0) in Zambia to 80.0% (95% CI 51.0–93.9) in Guatemala. At the late time point, among people failing NNRTI-based first-line ART, NNRTI resistance ranged from 84.3 (95% CI 69.4–92.7) in Guatemala to 89.5% (95% CI 71.0–96.7) in Cameroon. High levels of resistance in people with unsuppressed viral load indicate the need for rapid switch to effective second-line regimens. However, ADR surveys show that the use of PI regimens was low across all countries, suggesting inadequate switch to PI-based ART in people failing first-line NNRTI-based ART.
  • Additional data from the PHIA surveys conducted in Malawi, Zambia and Zimbabwe suggest high levels of viral load suppression among people who self-report being on ART for a variable range of time. In this population, the prevalence of viral load suppression ranged from 86% in Zimbabwe to 91% in Malawi among adults aged 15–59 years, suggesting that ART regimens are effective for the majority of individuals who report being on treatment in these countries.
  • Despite the high levels of ADR observed in national surveys and supported by a review of the published literature, the mutations and mutation patterns observed among people failing treatment suggest that currently recommended PI-based second-line ART remains an effective option for most people failing first-line ART. Nonetheless, strategic use of increasingly affordable drugs with higher barriers to development of resistance (e.g. dolutegravir) has the potential to mitigate concerns regarding ongoing treatment efficacy of NNRTI-based therapy, and may possibly reverse the observed trend of increasing NNRTI resistance.
  • As of December 2016, 19.5 million people were receiving ART globally, and over the next decade, ever-larger numbers of people must initiate and be successfully maintained on HIV treatment for life, to achieve global targets for epidemic control. To date, several countries have reported high levels of viral load suppression among people receiving treatment, attesting to the effectiveness of available therapy and the success of ART scale-up. The fact that “the third 90” target is being achieved in several countries is reassuring. However, in other countries viral load suppression in people on ART is well below the global target, and merits attention.
  • This global report demonstrates that levels of PDR are increasing, mostly driven by increasing levels of NNRTI resistance. Although levels of NNRTI PDR have reached above 10% in some of the countries surveyed, viral load and TDR prevalence estimates from the PHIA surveys suggest high levels of viral load suppression among people retained in care who self-report taking ART. Taken together, these data are consistent, and indicate that the majority of PLHIV who are taking ART are likely to control their infection. However, in several countries, significant and increasing proportions of people are infected with a virus resistant to NNRTI, and are therefore significantly less likely to achieve viral suppression when they start ART. In addition, a proportion of people receiving ART may not adhere to it due to individual-, clinic- or programme-level factors, and may therefore develop NNRTI resistance. High levels of NNRTI PDR have the potential to undermine the future success of global ART scale-up; therefore, this report underscores the need to strengthen the quality of HIV programmes to prevent further increases in HIVDR, to monitor when levels of resistance are unknown, and to respond to HIVDR when levels are high.
  • Preventing, monitoring and responding to HIVDR form the basis of the Global Action Plan on HIV drug resistance, a five-year framework for action spearheaded by WHO, which engages global and local stakeholders in a coordinated and resourced response to HIVDR. The Global Action Plan focuses on five strategic objectives: 1) prevention of and response to HIVDR; 2) monitoring of HIVDR through surveillance and routine programmatic data; 3) research and innovation; 4) laboratory capacity; and 5) governance and enabling mechanisms. The Global Action Plan articulates a global consensus and commitment to minimizing AMR and preventing HIVDR from undermining attainment of global HIV targets, including an AIDS-free generation by 2030.
  • The treatment landscape of HIV is rapidly evolving with introduction of new classes of drugs which are becoming available and more affordable in LMIC. As new drugs become available ongoing surveillance in real world settings will be required to preserve their long term efficacy and durability.

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{1} Argentina (PDR survey), Brazil (PDR survey), Cameroon (PDR and ADR surveys), Colombia (PDR survey), Guatemala (PDR and ADR surveys), Mexico (PDR survey), Myanmar (PDR survey), Namibia (PDR survey), Nicaragua (PDR survey), South Africa (HIVDR survey in children <18 months), Uganda (PDR survey), Viet Nam (ADR survey), Zambia (ADR survey) and Zimbabwe (PDR survey).

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Keywords: WHO; Updates; HIV/AIDS; Antivirals; Drugs Resistance.

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