This Week in HIV Research: Weighing Anchor on NRTI-Free Treatment

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Once again, we set sail through the vast ocean of medical journals in search of new insights into HIV care and treatment. This week, our voyage travels into little-explored inlets of research, as we seek to answer the following questions:

  • Is NRTI-free treatment truly a viable long-term option for people with multidrug resistance?
  • What factors are associated with a greater likelihood that a person will stop HIV treatment?
  • How has frailty risk evolved alongside the HIV epidemic among older people?
  • Where are we trending with skin and soft tissue infections among people with HIV?

Come aboard and take a deeper dive into the latest answers to each of these questions. To beat HIV, you have to follow the science!

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NRTI-Free Salvage Therapy Effective Long-Term

Salvage therapy without nucleoside reverse transcriptase inhibitors (NRTIs) is a viable, lasting HIV treatment option, according to final results from the OPTIONS trial that were published in Journal of Infectious Diseases.

Earlier results from the OPTIONS trial had found similar likelihoods of treatment failure in the "Add NRTIs" (181 participants, 26% probability) and "Omit NRTIs" (179 participants, 30% probability) arms at 48 weeks, provided the regimen included more than two active antiretrovirals. The newly published results, which extend the findings through week 96, find that 65% in the Add arm and 70% in the Omit arm had a viral load below 200 copies/mL when more than two active antiretrovirals were present. (Viral suppression was also achieved among 53% of a subgroup of 53 participants who had two or fewer active HIV drugs left and whose regimen included NRTIs.) Virologic failure was more likely in younger participants and those taking fewer new medications.

A related commentary by University of California-San Diego researchers Martin Hoenigl, M.D., and Susan Little, M.D., noted that 95% in the Add NRTIs group took tenofovir disoproxil fumarate (TDF), suggesting that results may be specific to that medication and may differ if newer drugs, such as tenofovir alafenamide (TAF), were used. However, they agreed with the study authors' conclusion that effective long-term salvage therapy without NRTIs is possible if it includes more than two active drugs.

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Age, Education Associated With HIV Treatment Interruption Risk

Younger people and those with less education are more likely to interrupt HIV treatment, an analysis of data from the multinational START trial that was published in AIDS found.

START randomized participants to begin antiretrovirals immediately or wait until their HIV disease had progressed to a specified point. Overall, 13% of the 2,286 participants in the immediate antiretroviral therapy arm and 11% of 1,152 people in the deferred start arm interrupted HIV treatment at least once. On average, interruptions began after five months on ART and lasted between three and 15 weeks. Among participants under 35 years old, 15% in the immediate and 11% in the deferred arm discontinued antiretrovirals, compared to 9% and 5%, respectively, of people over 50 years old.

Study authors theorized that younger people may have less housing and social stability, making treatment adherence more difficult. They also noted that the level of formal education could be a proxy for socioeconomic status, which might explain the association of education and treatment interruption. "There is a need to strengthen adherence advice and wider social support in younger people and those of lower education status," they concluded.

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Frailty Risk Grows Among Older People With HIV

Among people living with HIV, the prevalence of frailty has dropped in 50-year-olds but increased in 75-year-olds over the last decade, a retrospective study at a specialist clinic in Italy that was published in Open Forum Infectious Diseases showed.

The clinic manages non-communicable diseases, multimorbidity, and frailty in people living with HIV; data were provided on 3,321 clinic patients. Researchers computed a frailty index from 37 routinely collected variables and assigned participants to 3 groups: fit (index < 0.3), frail (index 0.31-0.39), or frailest (index > 0.4). They then developed a frailty compression ratio (FCR), defined as the ratio between the probability of being in the frailest group at age 75 versus at age 50.

Overall, the proportion of people classified as frailest dropped from 33% in 2006 to 16% in 2017, the researchers found. At age 50, the odds of being classified as frailest fell from 41% in 2006 to 36% in 2017; by contrast, at age 75, those odds rose from 23% in 2006 to 69% in 2017. The cumulative FCR was found to rise from 0.56 in 2006 to 1.89 in 2017. The observed results may be related to earlier treatment initiation among people with HIV in more recent years, the researchers noted. They concluded: “This immunological benefit may counteract any possible [antiretroviral]-related toxicity and be the main driver of the shift in onset of frailty toward an older age.” They also argued that using FCR as a metric for measuring frailty may be useful for evaluating the effect of public health interventions, as well as new drugs or treatment strategies.

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Skin, Soft Tissue Infections Decline in Houston, But Remain Prevalent

Rates of skin and soft tissue infections declined by 40% over five years in the Houston, Texas, public health system, researchers reported in Clinical Infectious Diseases. However, such infections remained common: A total of 2,202 such infections were treated in 8,597 people receiving HIV primary care between 2009 and 2014.

Twenty-three percent of the 2,202 infections were cultured, and 70% of the 331 S. aurens isolates with antibiotic susceptibilities were found to be resistant to methicillin (i.e., were MRSA), a proportion that remained stable over the study period.

Low CD4 cell count and high viral load predicted infection. An inverse relationship was also found between infection risk and being a Spanish-speaking Latinx person. Study authors theorized that this could be due to separate social networks within that community which limit exposure to bacteria from the wider population; alternatively, they hypothesized it may be because Spanish speakers are less likely to seek health care for such infections and instead self-treat with antibiotics received informally.

The study authors cautioned that their research relied on language data taken from medical records that was intended to flag the need for translation services, which may not accurately reflect a person’s preferred language. They called for further study into the reasons for skin and soft tissue infections in people living with HIV.