HIV Treatment Schedules Under Scrutiny

Intermittent Dosing Shows Promise for Adults, But Risks Adolescents

New research presented at the International AIDS Society Conference on HIV Science suggests that skipping antiretroviral drug doses on weekends may be a viable option for adults with well-controlled HIV. However, the same intermittent approach appears detrimental for adolescents in Africa, particularly those with limited access to regular viral load testing.

Adults Show Virological Stability with Intermittent Treatment

A comprehensive review analyzing data from eight randomized trials found no significant difference in virological suppression between adults on continuous daily HIV treatment and those on intermittent schedules. Participants in both groups experienced viral rebound at similar rates, approximately 3%. The studies, which included regimens based on NNRTIs, bictegravir, emtricitabine, and tenofovir alafenamide, also revealed comparable rates of treatment-emergent drug resistance between the two approaches (1.9% for intermittent vs. 2.1% for continuous treatment).

The proposed intermittent treatment schedules, such as taking medication five days on and two days off, aim to alleviate the long-term adherence burden for some individuals living with HIV. This strategy has gained traction amidst concerns over antiretroviral drug supply chain disruptions. A UNAIDS survey highlighted that nearly half of 56 countries affected by funding cuts reported supply chain issues, with 14% having less than six months of stock for at least one antiretroviral drug.

Dr. Cassandra Fairhead of the Royal Free Hospital, London, led the systematic review and pooled analysis. The research examined 1346 participants, all of whom had suppressed viral loads at the study’s outset. The review excluded pregnant women and, with one exception, individuals with hepatitis B. While intermittent treatment is not currently recommended by any national or international guidelines, these findings suggest a potential adaptation for specific patient groups.

Adolescents Face Increased Viral Rebound Risk

In stark contrast, the BREATHER Plus study’s 96-week results indicate that intermittent treatment is inferior for adolescents with HIV in sub-Saharan Africa. This study randomized 470 adolescents, with a median age of 16.5 years, to either continue their daily tenofovir disoproxil, lamivudine, and dolutegravir (TLD) regimen or switch to a five-days-on, two-days-off schedule. The majority of participants acquired HIV through vertical transmission and had been on antiretroviral therapy for over a decade.

The study revealed a significantly higher rate of viral rebound in the intermittent treatment arm. Ten percent of participants on continuous treatment experienced viral rebound, compared to 5% in the intermittent arm—a difference of 5.1% (p=0.034). Kaplan-Meier analysis showed that adolescents on intermittent treatment were more than twice as likely to experience viral rebound after 96 weeks.

“Intermittent treatment cannot be recommended as a treatment strategy for adolescents with HIV taking TLD and receiving viral load tests every six to 12 months,” the study investigators concluded. The limited frequency of viral load monitoring in these settings may delay the detection of treatment failure, potentially exacerbating viral rebound and resistance.

A recent report from the World Health Organization indicates that in 2022, approximately 990,000 children under 15 years were living with HIV globally, with a significant proportion residing in sub-Saharan Africa (WHO, 2023). This highlights the critical need for effective and safe treatment strategies tailored to this vulnerable population.

The BREATHER Plus study’s adherence sub-study, utilizing electronic pill bottles, found that tablets were taken correctly on 92% of study days in both arms over 24 weeks, suggesting adherence itself was not the primary driver of the differential outcomes.

Dr. Kekitiinwa A, a key researcher in the BREATHER Plus study, presented the findings, emphasizing the distinct needs of adolescent populations. The concern is that in settings with less frequent viral load monitoring, any switch to intermittent therapy could lead to a more rapid increase in viral rebound and drug resistance if treatment failure occurs.