Impact of HIV Drug Resistance on HIV/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub–Saharan Africa

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Abstract

To inform the level of attention to be given by antiretroviral therapy (ART) programs to HIV drug resistance (HIVDR), we used an individual-level model to estimate its impact on future AIDS deaths, HIV incidence, and ART program costs in sub–Saharan Africa (SSA) for a range of program situations. We applied this to SSA through the Spectrum-Goals model. In a situation in which current levels of pretreatment HIVDR are over 10% (mean, 15%), 16% of AIDS deaths (890 000 deaths), 9% of new infections (450 000), and 8% ($6.5 billion) of ART program costs in SSA in 2016–2030 will be attributable to HIVDR.

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Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis

Ravindra K. Gupta, Michael R. Jordan, Binta Sultan … (2012)

Summary Background The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings. Methods We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models. Findings Study-level data were available for 26 102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (–0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0·0001) and southern Africa (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region. Interpretation Our findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The findings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention efforts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middle-income countries—no changes in antiretroviral treatment guidelines are warranted at the moment. Funding Bill & Melinda Gates Foundation and the European Community's Seventh Framework Programme

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Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Linda Wittkop, Huldrych F Günthard, Frank de Wolf … (2011)

The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Of 10,056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. European Community's Seventh Framework Programme FP7/2007-2013 and Gilead. Copyright © 2011 Elsevier Ltd. All rights reserved.

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What Is Required to End the AIDS Epidemic as a Public Health Threat by 2030? The Cost and Impact of the Fast-Track Approach

John Stover, Lori Bollinger, José Antonio Izazola-Licea … (2016)

In 2011 a new Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and AIDS-related deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services for 2015, resulting in a reduction of new HIV infections by more than half, in line with the goals of the declaration of the UN High Level Meeting in June 2011. However, the approach suggested a leveling in the number of new infections at about 1 million annually—far from the UNAIDS goal of ending AIDS by 2030. In response, UNAIDS has developed the Fast-Track approach that is intended to provide a roadmap to the actions required to achieve this goal. The Fast-Track approach is predicated on a rapid scale-up of focused, effective prevention and treatment services over the next 5 years and then maintaining a high level of programme implementation until 2030. Fast-Track aims to reduce new infections and AIDS-related deaths by 90% from 2010 to 2030 and proposes a set of biomedical, behavioral and enabling intervention targets for 2020 and 2030 to achieve that goal, including the rapid scale-up initiative for antiretroviral treatment known as 90-90-90. Compared to a counterfactual scenario of constant coverage for all services at early-2015 levels, the Fast-Track approach would avert 18 million HIV infections and 11 million deaths from 2016 to 2030 globally. This paper describes the analysis that produced these targets and the estimated resources needed to achieve them in low- and middle-income countries. It indicates that it is possible to achieve these goals with a significant push to achieve rapid scale-up of key interventions between now and 2020. The annual resources required from all sources would rise to US$7.4Bn in low-income countries, US$8.2Bn in lower middle-income countries and US$10.5Bn in upper-middle-income-countries by 2020 before declining approximately 9% by 2030.

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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J. Infect. Dis

Journal ID (publisher-id): jid

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press (US )

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date (Print): 01 May 2017

Publication date (Electronic): 17 February 2017

Publication date PMC-release: 17 February 2017

Volume: 215

Issue: 9

Pages: 1362-1365

Affiliations

[1 ]Institute for Global Health , University College London, United Kingdom;

[2 ]Avenir Health , Glastonbury, Connecticut;

[3 ]Tufts University School of Medicine , Boston, Massachusetts;

[4 ]African Health Research Institute, KwaZulu-Natal, South Africa and Division of Infection and Immunity , University College London, United Kingdom;

[5 ]World Health Organisation , Geneva, Switzerland; and

[6 ]Centre for Health Economics, University of York , United Kingdom

Author notes

Correspondence: A. N. Phillips, PhD, FMedSci, Institute for Global Health, University College London (UCL), Royal Free Campus, London NW3 2PF, UK ( andrew.phillips@ 123456ucl.ac.uk ).

Article

Publisher ID: jix089

DOI: 10.1093/infdis/jix089

PMC ID: 5451603

PubMed ID: 28329236

SO-VID: b8e05ea3-1741-456f-af90-5cc8ea8e7844

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 13 November 2016

Date accepted : 15 February 2017

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Impact of HIV Drug Resistance on HIV/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub–Saharan Africa

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 13

Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

What Is Required to End the AIDS Epidemic as a Public Health Threat by 2030? The Cost and Impact of the Fast-Track Approach

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