A surreal illustration depicting the global challenge of HIV drug resistance.

HIV Drug Resistance: An Emerging Global Challenge

Soraya Malik in Health & Wellness December 2025 • 5 min read.

"Understanding the rise of HIV drug resistance in low- and middle-income countries and strategies to combat it for a healthier future."

For over 15 years, the global effort to combat HIV through antiretroviral therapy (ART) has seen remarkable success. However, a significant challenge is emerging: the increasing prevalence of HIV drug resistance, particularly in low- and middle-income countries (LMICs). This resistance threatens to undermine the progress made, potentially leading to increased mortality, higher HIV incidence, and greater costs for healthcare systems.

To achieve the ambitious UNAIDS global targets for combating HIV, enhanced strategies are essential. These include improving the quality of ART services, ensuring the durability of available ART regimens, and actively working to curb the development of resistance. Strategies also include the rollout of drugs with greater efficacy and higher genetic barriers to resistance, as well as ensuring universal access to viral load monitoring, reliable drug supply chains, and patient-centered care models.

This article will examine the contemporary data on HIV drug resistance in LMICs, exploring the implications for the global HIV response. It will also highlight the potential impact and the resistance risks associated with novel ART strategies, identifying existing knowledge gaps and areas for further research.

The Rising Threat of HIV Drug Resistance

A surreal illustration depicting the global challenge of HIV drug resistance.

The global scale-up of antiretroviral therapy (ART) has been a game-changer in the fight against HIV, averting an estimated 7.8 million deaths and preventing 30 million new infections in low- and middle-income countries (LMICs) between 2004 and 2014. Today, over 21 million people with HIV are receiving ART, representing just over half of all people infected worldwide. A significant majority – nine out of ten – of those living with HIV reside in LMICs, primarily in sub-Saharan Africa and Asia, regions that bear the brunt of the global epidemic.

The World Health Organization (WHO) has championed a public health approach to ART, emphasizing simplified and standardized treatment protocols. This approach aims to facilitate effective care delivery, particularly in settings where clinical expertise and access to antiretroviral drugs and laboratory monitoring are limited. The goal is ambitious: to end the AIDS pandemic as a public health threat by 2030.

The 90-90-90 Targets: By 2020, ensure that 90% of people with HIV know their HIV status, 90% of those infected are receiving ART, and 90% of those on ART have sustained viral suppression.
Sustained Viral Suppression: A key factor in maximizing individual health and survival, as well as reducing HIV incidence.
Lifelong Commitment: The need to successfully maintain individuals on effective ART for life to achieve global targets.

After 15 years of ART scale-up, an alarming trend is emerging: rising HIV resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in many LMICs. First-generation NNRTIs like efavirenz and nevirapine remain the cornerstone of first-line therapy and peripartum prophylaxis. These drugs are highly susceptible to resistance because of their low genetic barrier; a single mutation can result in complete loss of drug activity. Forecasts predict that the global rise in HIV drug resistance could lead to increased mortality, higher HIV incidence, and greater costs for ART programs if changes are not made to the standards of care in many LMICs.

Charting a Course for the Future

Rising HIV drug resistance poses a significant threat to the achievements made in controlling the epidemic. The commitment of policymakers and national governments is crucial to achieving global HIV targets. While substantial knowledge gaps remain in addressing resistance in LMICs, a range of measures can be taken to minimize HIV drug resistance and maintain global HIV control. The rollout of fixed-dose combination therapies provides a unique opportunity to improve treatment outcomes, provided it is implemented with improved quality of services and appropriate monitoring frameworks. Through continued research, innovation, and collaboration, we can chart a course towards a future where HIV drug resistance is effectively managed, and the global HIV targets are within reach.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/s2352-3018(18)30173-5, Alternate LINK

Title: Hiv Drug Resistance In Low-Income And Middle-Income Countries

Subject: Virology

Journal: The Lancet HIV

Publisher: Elsevier BV

Authors: Raph L Hamers, Tobias F Rinke De Wit, Charles B Holmes

Published: 2018-10-01

Everything You Need To Know

What exactly does HIV drug resistance mean, and why is it becoming such a big problem?

HIV drug resistance occurs when the virus mutates in such a way that antiretroviral drugs (ART) become less effective at suppressing it. This means the drugs can no longer prevent the virus from replicating and potentially causing further damage to the immune system. The rise of HIV drug resistance is especially concerning because it can lead to treatment failure, increased HIV incidence, and higher healthcare costs. Additionally, certain classes of drugs, like non-nucleoside reverse-transcriptase inhibitors (NNRTIs), are particularly prone to resistance due to their low genetic barrier.

What are the UNAIDS global targets, and why are they so important in the effort to control HIV?

The UNAIDS global targets, specifically the 90-90-90 targets, are crucial benchmarks in the fight against HIV. These targets aim to ensure that by 2020, 90% of people with HIV know their status, 90% of those infected are receiving ART, and 90% of those on ART have sustained viral suppression. Achieving these targets is significant because they directly impact individual health outcomes, reduce HIV incidence, and contribute to ending the AIDS pandemic. The concept of sustained viral suppression is key to maximizing individual health and survival, as well as reducing HIV incidence.

What is antiretroviral therapy (ART), and how does it help people living with HIV?

Antiretroviral therapy (ART) is a treatment that uses drugs to suppress the HIV virus, slowing its progression and helping people with HIV live longer, healthier lives. Over 21 million people with HIV are currently receiving ART globally. ART is a lifelong commitment, it helps individuals to achieve sustained viral suppression. If ART fails due to drug resistance, individuals may experience disease progression and become more likely to transmit the virus to others. Strategies to improve ART include enhancing the quality of services, ensuring the durability of available regimens, and using drugs with greater efficacy.

What are non-nucleoside reverse-transcriptase inhibitors (NNRTIs), and why are they so prone to resistance?

Non-nucleoside reverse-transcriptase inhibitors, or NNRTIs, are a class of antiretroviral drugs commonly used as a first-line treatment for HIV. Drugs like efavirenz and nevirapine fall into this category. NNRTIs are highly susceptible to resistance because they have a low genetic barrier, meaning that a single mutation in the virus can render them ineffective. The rising resistance to NNRTIs is a significant concern because these drugs are often the cornerstone of initial treatment regimens, especially in resource-limited settings.

What are fixed-dose combination therapies, and how do they play a role in managing HIV treatment?

Fixed-dose combination therapies involve combining multiple antiretroviral drugs into a single pill. This approach can improve adherence to treatment by simplifying the dosing schedule. However, the success of fixed-dose combination therapies depends on the quality of healthcare services and monitoring frameworks. If resistance develops to one component of the combination, the entire regimen may fail. Ensuring appropriate monitoring and quality services is crucial to maximizing the benefits of fixed-dose combination therapies.