#554 - New for HIV Prevention, Cancer Prevention, Time for Some Intimacy?

From the Literature

1)  Another Option for HIV Prevention?

The US Preventive Services Task Force has recommended pre-exposure prophylaxis (PrEP) for HIV prevention since 2019. The wording of the recommendation included the term “effective antiretroviral therapy,” to allow for newer medications that would be produced after the recommendation (rather than specify the Emtricitabine / Tenofovir Disoproxil Fumarate (F/TDF) combination (Truvada) on which the initial recommendation was based). Adherence issues associated with the daily oral F/TDF regimen were a major focus of the recommendation, as efficacy dropped off dramatically under 70% adherence. Emtricitabine/tenofovir alafenamide fumarate (F/TAF) (Descovy) was deemed effective soon after the recommendation, and more recently a bimonthly injection of cabotegravir was approved.

A new study of twice-yearly injectable Lenacapavir has just been published. The study compared the newer lenacapavir with F/TAF with the active control (F/TDF). They also compared the rate of new infections on these medications with the “background rate of infections” in the population of adolescents and young women in South Africa and Uganda. The study was thoughtful and overall well-done. It was funded by the makers of Truvada and Descovy. Part of the backstory here was that the initial Descovy trials did not include cis gender women as participants, and Gilead received some criticism for that. This new study is an attempt to recover that ground by studying both lenacapavir and F/TAF compared to F/TDF in cis gender women specifically.

There were 5345 participants randomized and 5338 analyzed. Over the year of treatment, the background (no prophylaxis) rate of HIV was 2.41 per 100 person-years, the per 100 person-year rates for F/TDF, F/TAF, and lenacapavir were 1.69, 2.02 and zero. That’s right, zero infections in the study for lenacapavir. Also, importantly, rates for the F/TAF group were not meaningfully different than the background rate of infection. Other STI rates were high and similar between groups. Post-hoc analysis revealed lower rates of HIV incidence with higher rates of adherence with F/TAF and F/TDF- confirming the lesson from the first F/TDF trials. There were more injection site reactions with lenacapavir than with the other drugs, but few withdrawals due to those and gastrointestinal and renal side effects were less than the oral medications.

John’s Comments:

HIV prevention is important but is also complex and changes frequently as evidence accumulates. I would recommend the CDC HIV PrEP guidelines as the most up to date source to ensure that you’re thinking of all the right things (e.g., when to start PrEP, how to monitor treatment, other testing to consider, etc.). Lenacapavir has not yet made it into these guidelines.

Remember, the best way to ask about risk in a patient for whom you’re considering PrEP is to ask about specific risky behaviors – “How many sexual partners have you had in the last year?”, or “Do you have anal receptive intercourse?” This enables you to learn about true risk factors without getting lost in not-specific-enough labels associated with identity (gay, straight, etc.)

Reference:

• Bekker LG, Das M, Karim QA, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. New England Journal of Medicine. 0(0). Link

From the Literature and the American Cancer Society

2)  Modifiable Risk Factors for Cancer Prevention

Cancer prevention and early detection are central to the mission of both primary care medicine and public health.  Large reductions in smoking and improvements in earlier cancer detection have contributed to steady declines in cancer mortality since the early 1990s, averting an estimated 3.8 million cancer deaths.  In 2014, an estimated 42% of cancer cases and 45% of cancer deaths in the US could be attributed to modifiable risk factors.  Furthermore, cancer screening tests can prevent thousands of additional cancer cases and deaths through identification and removal of premalignant abnormalities (colorectal and cervical) and detection of cancers at an early stage when treatment is more effective.

A recently published paper updated these estimates based on the proportion and number of invasive cancer cases (excluding nonmelanoma skin cancers) and deaths, overall and for 30 cancer types among adults who were aged > 30 in 2019 in the US, that were attributable to potentially modifiable risk factors.  The researchers used an accepted formula to estimate the population-attributable fraction (PAF; i.e., the proportion of cancer attributable to risk factors in the population) for each risk factor and associated cancer in each stratum of sex and age group. 

Risk factors included cigarette smoking; second-hand smoke; excess body weight; alcohol consumption; consumption of red and processed meat; low consumption of fruits and vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and seven carcinogenic infections. Numbers of cancer cases and deaths were obtained from data sources with complete national coverage, risk factor prevalence estimates from national surveys, and associated relative risks of cancer from published large-scale pooled or meta-analyses.

They found that in 2019, an estimated 40% of all incident cancers (excluding nonmelanoma skin cancers) and 44% of all cancer deaths were attributable to the evaluated risk factors.  Cigarette smoking was the leading risk factor contributing to cancer cases and deaths overall (19.3% and 28.5%, respectively), followed by excess body weight (7.6% and 7.3%, respectively), and alcohol consumption (5.4% and 4.1%, respectively). For 19 of 30 evaluated cancer types, more than one half of the cancer cases and deaths were attributable to the potentially modifiable risk factors considered in this study.  Lung cancer had the highest number of attributed cancer cases and deaths, followed by female breast cancer, skin melanoma, and colorectal cancer for attributed cases and by colorectal, liver, and esophageal cancer for attributable deaths.

The authors concluded these findings reinforce that the morbidity and premature mortality from cancer in the US can be substantially reduced through broad and equitable implementation of known preventive initiatives, such as excise taxes on cigarettes to reduce smoking, screening for and treating HCV infection, and vaccination against HPV infection.  They note that further implementation research is needed for broad application of known interventions, particularly for excess body weight, unhealthy diet, alcohol consumption, and physical inactivity.   

Mark’s Comments:

It is encouraging to see how attention to risk factor reduction can have a profound impact on modifying these risk factors.  For example, current smoking has declined from 20.9% in 2005 to 11.5% in 2021.  Cervical cancer is estimated to be 100% preventable based on this study.  The authors note that further research is also needed on the association between potentially modifiable risk factors and cancers for which the current evidence for causality in humans is limited; on common cancers with few established modifiable risk factors (e.g., prostate cancer and non-Hodgkin lymphoma); on other potentially modifiable exposures, such as occupational carcinogens, air pollution, and other environmental risk factors; on associations of exposures throughout the lifetime; and on interactions between risk factors. 

These are exciting times here at Carilion Clinic as we prepare to break ground on a new cancer center.  At the same time, I am also hoping that some of our efforts (and resources) can also be devoted to finding and more effectively implementing ways to prevent those cancers in the first place.  There appears to be plenty of opportunities.

References:

• Islami F, et al.  Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019.  CA Cancer J Clin. Published ahead of Print July 1, 2024. 1–28.  Link
• American Cancer Society:  Cancer Prevention and Early Detection – Facts and Figures 2023-2024.  December 2023.  Link

From PeerRxMed ( www.PeerRxMed.org )

3)  Asking Powerful Questions to Build Professional Intimacy

"Intimacy is the willingness to be vulnerable." – Brené Brown

Who is a colleague who knows you well?  As I reflect on my professional friendships where others “know me best,” at some point we have explored together the questions that matter most to each of us.  While initially our conversations were limited to work-related topics and casual banter, over time we began to share aspects of ourselves we hadn’t previously revealed, including our struggles, our fears, our hopes, our dreams, and the “bigger” questions of life for us, particularly those regarding purpose and meaning.   

However, in our fast-paced and perpetually demanding world of healthcare, forming deep, meaningful friendships can be challenging, even as we know these connections are vital for our emotional support and professional well-being.  “I don’t have time” is the most common reason for not having such bonds, but if it were simply a matter of time, we would likely feel closely connected with those we’ve worked alongside for countless hours, often over many years.  What then is the often-missing ingredient for developing such relationships?   

Psychologist Arthur Aron’s research on intimacy-building highlights the importance of asking (and answering) the right questions to foster these bonds.  While the word “intimacy” may initially seem off-putting (“I’m not seeking intimacy with my colleagues!”), it is important to remember that the Latin origins of the word intimacy (intimis/intimatus) mean “inmost” and “to make known” – or what I have come to understand as “into-me-see.” 

In this particular study, randomly paired participants were given a series of 36 progressively intimate questions to both ask and answer over 45 minutes.  The questions were designed to encourage mutual self-disclosure and ranged from light-hearted  (“When did you last sing to yourself?”) to more deeply personal (“What’s your most treasured memory?” and “When did you last cry in front of another person?”).  Results demonstrated that by using this more intentional process, interpersonal connections were consistently deepened compared to those who engaged in small talk. 

Building our professional friendships requires more than just shared experiences; it demands intentionality and vulnerability.  Dr. Aron’s intimacy-building questions offer a practical tool for fostering these connections.  I challenge you to integrate some of his questions into your conversations with your PeerRx partner or another colleague and experience how the dialogue helps transform your interactions – and your relationship.  Here's a structured process that might be useful and includes the 36 questions, though I would encourage you to savor these questions and answer them together over many weeks rather than all at once.  By embracing the art of asking and answering good questions, you can build stronger, more intimate friendships that enrich your professional (and personal) life.  That sounds like a wonderful reason to reconsider “professional intimacy.”

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org