Hepatitis C cure can be assessed 4 weeks after treatment – European AIDS Treatment Group

Report on the 96-Week Efficacy and Safety of Long-Acting Injectable HIV Therapy in Africa

Executive Summary

This report details the 96-week findings of a phase 3b trial evaluating a long-acting injectable (LAI) HIV therapy, comprising cabotegravir and rilpivirine, in African populations. The study demonstrates that the 8-weekly injectable regimen is noninferior to standard daily oral therapy in maintaining viral suppression. These results provide crucial evidence of the regimen’s durability and safety, supporting its potential integration into African HIV treatment programs. The findings directly contribute to the United Nations Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health and Well-being) by advancing efforts to end the AIDS epidemic, SDG 10 (Reduced Inequalities) by validating an advanced treatment option for resource-limited settings, and SDG 5 (Gender Equality) by providing specific data on outcomes in women, who represent a majority of participants.

Introduction: Aligning HIV Treatment with Sustainable Development Goals

The global effort to combat the HIV epidemic, a core component of SDG 3.3, relies on effective and sustainable antiretroviral therapy. While standard oral regimens are highly effective, long-acting therapies offer a valuable alternative that may improve treatment satisfaction and adherence. This study provides a definitive evaluation of an 8-weekly LAI regimen in a sub-Saharan African context, a region central to the global HIV response. The research assesses the durability, safety, and suitability of this innovative therapy within a public health framework, aiming to provide evidence that can reduce health disparities and advance global health equity, in line with SDG 10.

Methodology: A Framework for Equitable Health Research

The study was a prospective, multicenter, randomized, open-label, noninferiority trial conducted over 96 weeks across eight sites in Uganda, Kenya, and South Africa. This approach ensures that findings are relevant to the populations most affected by HIV, directly addressing the principles of SDG 10.

Trial Design and Participants

• Participants: 512 African adults with HIV-1, virologically suppressed on standard first-line oral therapy.
• Randomization: Participants were randomized 1:1 to either continue standard oral therapy or switch to LAI cabotegravir (600 mg) and rilpivirine (900 mg) injections every 8 weeks.
• Monitoring: Viral load was monitored every 24 weeks, simulating conditions typical of public health programs in the region.
• Primary Outcome: The primary outcome for this 96-week analysis was the proportion of participants with a plasma viral load of less than 50 copies/mL.

Key Findings and Efficacy Analysis

The trial’s results demonstrate the long-term effectiveness of the LAI regimen, providing a strong foundation for its consideration in public health strategies aimed at achieving SDG 3.3.

Virologic Suppression and Contribution to SDG 3.3

1. Primary Efficacy: At 96 weeks, viral suppression (
2. Noninferiority: The treatment difference was -0.4% (95% CI -3.1% to 2.0%), successfully meeting the prespecified noninferiority margin of 10%. This confirms that the LAI regimen is as effective as the standard of care for maintaining viral suppression.

Virological Failure and Drug Resistance

• Confirmed Virological Failure (CVF): CVF occurred in 2% (4/255) of participants in the LAI group and in no participants in the oral therapy group. While the noninferiority criterion for this secondary outcome was not met, the overall rate of failure was low.
• Resistance Development: Of the participants with CVF in the LAI group, three had new resistance mutations to both cabotegravir and rilpivirine. Importantly, these participants were able to achieve viral resuppression after switching back to a standard oral regimen, suggesting that future treatment options under a public health approach remain viable.

Safety, Tolerability, and Gender-Specific Outcomes

The overall safety profile was acceptable, though the study identified important sex-specific metabolic changes that are critical for promoting gender equality in health outcomes, a key target of SDG 5.

Overall Safety Profile

• Adverse Events: Grade ≥3 adverse events occurred in 16% of the LAI group and 9% of the oral therapy group, with most considered unrelated to the study drug.
• Tolerability: Injection-site reactions were common (77%) but mostly mild (grade 1-2). Only one treatment-related adverse event (injection-site abscess) led to discontinuation of the LAI therapy.

Addressing Gender Equality in Health (SDG 5)

• Weight and Metabolic Changes: Women in the LAI group experienced greater increases in body weight, BMI, and incident obesity compared to women in the oral therapy group. They also showed a greater rise in total cholesterol and triglycerides.
• Implications: These findings underscore the importance of monitoring metabolic health, particularly in women, when implementing this regimen. Recognizing and managing these gender-specific outcomes is essential for ensuring equitable and effective care for all individuals living with HIV.

Implications for Public Health and SDG Alignment

The trial results have significant implications for the evolution of HIV care in resource-limited settings, supporting progress toward both SDG 3 and SDG 10.

Suitability for African Treatment Programs (SDG 10)

• Regimen Forgiveness: Efficacy was maintained even among the 10% of participants who experienced injection delays of more than 14 days, suggesting the regimen is robust enough for real-world program settings.
• Simplified Implementation: The study found that potential risk factors for virologic failure identified in other populations (e.g., viral subtype A1, obesity) were not associated with failure in this trial. This suggests that complex and costly baseline resistance testing may not be necessary, facilitating wider and more equitable access.

Enhancing Patient Well-being and Treatment Satisfaction

• Quality of Life: Overall quality of life was high and similar between both groups.
• Treatment Satisfaction: Satisfaction scores increased significantly more in the LAI group. Over 99% of participants in the LAI group expressed a preference for injectable therapy over daily oral pills, highlighting its potential to improve the well-being of people living with HIV.

Conclusion: Advancing Global Health through Collaborative Innovation

This trial provides definitive evidence that 8-weekly long-acting injectable cabotegravir and rilpivirine is a durable, effective, and well-tolerated option for HIV treatment in Africa. By demonstrating noninferiority to the standard of care and high patient preference, this research supports the adoption of new technologies that can help achieve the goals of SDG 3 (Good Health and Well-being). The study’s focus on a public health approach in a high-burden region promotes SDG 10 (Reduced Inequalities), while its detailed analysis of outcomes in women contributes to SDG 5 (Gender Equality). The successful collaboration between African and international researchers and funders also exemplifies the spirit of SDG 17 (Partnerships for the Goals), heralding a new era of patient-centered HIV care in the public health approach.

1. Which SDGs are addressed or connected to the issues highlighted in the article?

SDG 3: Good Health and Well-being

The article is fundamentally centered on health, specifically the treatment of HIV/AIDS. It evaluates a new long-acting injectable therapy to improve health outcomes for people living with HIV in Africa, directly contributing to the goal of ensuring healthy lives and promoting well-being.

SDG 10: Reduced Inequalities

The study addresses health inequalities by focusing on an African population, which has been underrepresented in previous trials for this therapy conducted “mainly in Europe and North America.” By generating evidence for “a population representative of those receiving treatment in the public health approach in sub-Saharan Africa, with a majority of participants being women,” the research aims to ensure that advanced medical treatments are effective and accessible for diverse populations, reducing disparities in health outcomes.

SDG 17: Partnerships for the Goals

The trial exemplifies a multi-stakeholder partnership. The acknowledgements section states that the trial was funded by Janssen, with drug donations from both Janssen and ViiV, and conducted by African research institutions like the Joint Clinical Research Centre in Uganda and sites in Kenya and South Africa. This collaboration between private industry and research institutions in developing countries is a clear example of a partnership to advance science, technology, and health goals.

2. What specific targets under those SDGs can be identified based on the article’s content?

SDG 3: Good Health and Well-being

• Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.

  The article’s entire focus is on improving HIV treatment to achieve and maintain viral suppression. The study’s primary outcome is “durable virologic suppression,” which is the cornerstone of HIV treatment strategies aimed at preventing disease progression and stopping transmission, thereby contributing directly to the goal of ending the AIDS epidemic.

• Target 3.8: Achieve universal health coverage, including … access to safe, effective, quality and affordable essential medicines … for all.

  The research evaluates a new long-acting therapy as a “valuable alternative to standard oral therapy in treatment programs in Africa.” By assessing its efficacy, safety, and patient preference, the study provides the evidence needed for this new treatment to be considered for inclusion in public health programs, thus expanding access to effective and quality essential medicines within the framework of universal health coverage.

SDG 10: Reduced Inequalities

• Target 10.3: Ensure equal opportunity and reduce inequalities of outcome…

  The article explicitly notes that previous trials were conducted in Europe and North America and that this trial provides the “definitive evaluation of long-acting therapy in a population representative of those receiving treatment in the public health approach in sub-Saharan Africa.” By generating specific evidence for African populations, the trial works to reduce inequalities in health outcomes and ensure that new medical innovations are suitable for all, not just populations in high-income countries.

SDG 17: Partnerships for the Goals

• Target 17.6: Enhance North-South, South-South and triangular regional and international cooperation on and access to science, technology and innovation…

  The trial is a direct result of a North-South partnership. As stated in the acknowledgements, pharmaceutical companies (Janssen, ViiV) provided funding and the drugs (technology), while research centers in Uganda, Kenya, and South Africa conducted the scientific research. This collaboration facilitates the transfer of and access to new medical technology and innovation in the African region.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Indicators for SDG 3 (Target 3.3)

The article provides several direct and implied indicators for measuring progress in combating AIDS:

• Viral Suppression Rate: This is a primary indicator of treatment effectiveness. The article states, “At 96 weeks, 247/255 (97%) in the long-acting group and 250/257 (97%) in the oral therapy group had VL
• Rate of Virological Failure: This measures the durability of the treatment. The article reports, “Confirmed virological failure… occurred in 4/255 (2%) participants in the long-acting therapy group and in no participants in the oral therapy group.” A low failure rate indicates a robust treatment option.
• Incidence of Drug Resistance: This is critical for the long-term sustainability of treatment programs. The article notes that among those with virological failure, “All three had new resistance mutations to both rilpivirine… and cabotegravir.” Monitoring resistance is essential to ensuring future treatment options remain viable.

Indicators for SDG 3 (Target 3.8)

The article implies indicators related to access to quality and effective medicines:

• Safety and Tolerability Profile: To be considered a quality medicine, a drug must be safe. The article measures this through adverse events: “Adverse events of grade 3 or greater severity occurred in 41/255 (16%) participants in the long-acting therapy group and 22/257 (9%) in the oral therapy group,” concluding an “acceptable safety and tolerability profile.”
• Patient Treatment Satisfaction and Preference: High satisfaction is an indicator of a treatment’s suitability and can predict adherence, which is crucial for effectiveness. The article reports, “Treatment satisfaction score increased more… in the long-acting therapy group… 243 (>99%) responded that they preferred long-acting therapy over oral therapy.”

Indicators for SDG 10 (Target 10.3)

The article implies an indicator for reducing inequalities in health research:

• Demographic Representation in Clinical Trials: The composition of the study population serves as an indicator of research equity. The article highlights its focus on “a population with a high proportion of women and Black participants, extensive prior exposure to NNRTI-containing regimens, and viral subtypes common in Africa,” thereby ensuring the findings are relevant to the most affected populations and reducing inequalities in evidence generation.

4. Create a table with three columns titled ‘SDGs, Targets and Indicators” to present the findings from analyzing the article.

Source: nature.com