Achieving viral suppression reduces morbidity and mortality from HIV-related and unrelated causes, while also playing an important role in preventing HIV transmission.1–3 In this article, Bush et al used clinical data at an outpatient site to describe the frequency of blips, defined as a HIV viral load >20 copies/mL.4 The magnitude of viremia during blips, time to return to viral suppression, management of viremia, and antiretroviral therapy (ART) adherence were not described which limit the interpretation of the data. Low-level viremia (LLV) has been defined as a single HIV viral load <200 copies/mL, followed by a return to a viral load below the lower limit of detection in adherent individuals.5 Broyles et al recently published a systemic review in August 2023 investigating sexual HIV transmission among individuals with LLV. Among 8 studies of 7762 discordant partners globally, no transmission events were identified when the partner with HIV had a viral load <200 copies/mL. Two potential transmissions were identified when the index partner's viral load was <1000 copies/mL; however, interpretation was limited by the timing of viral load testing. This suggests that HIV transmission is low when the viral load is <1000 copies/mL and HIV is untransmittable when the viral load is undetectable at <200 copies/mL.6 When evaluating LLV, it is critical to consider ART adherence. The significance of viremia may differ in those who are not fully adherent to their medication, increasing the risk of virologic failure, compared with those who are fully adherent and experience isolated blips that return to undetectable without intervention.

As the authors point out, despite the robust evidence that Undetectable = Untransmittable (U=U), transmission of sexually transmitted infections (STIs) remains a critical concern. Increases in STIs may be driven by decreased condom use in the setting of widespread acceptance of U=U and increased availability of HIV pre-exposure prophylaxis (PrEP), as well as due to COVID-19 related disruptions to critical sexual health services.7,8 In the United States, there were over 2.5 million cases of syphilis, gonorrhea, and chlamydia reported in 2022.9 In addition, recent outbreaks of sexually transmitted Mpox have occurred, which have disproportionately affected men who have sex with men and persons with HIV.10 Sexually transmitted infections are very costly to the healthcare system and can cause serious morbidity, including neurologic/ocular complications in the case of syphilis, as well as contribute to pelvic inflammatory disease and infertility in women. Ulcerative anogenital infections are of significant importance as they have been shown to enhance the risk HIV transmission in serodiscordant couples when the partner with HIV is not on suppressive ART.11 Fortunately, both the PARTNER and Opposites Attract study provided reassuring data that U=U even in the presence of STIs, with no HIV transmissions occurring when either partner had an STI.2,3

Convenient and efficient access to STI testing (including home testing) and treatment, expedited partner therapy, and provision of PrEP should be incorporated into comprehensive strategies to combat the HIV and STI syndemic. Furthermore, doxycycline postexposure prophylaxis (doxy-PEP) has been shown to reduce risks of syphilis, chlamydia, and gonorrhea in men who have sex with men and transgender women.12 In clinical practice, integrating doxy-PEP into standard PrEP care has resulted in strong uptake and is a high impact intervention resulting in the rapid decline of STI incidence.13 Promoting U=U should not diminish the emphasis on STI screening and prevention strategies. Instead, a holistic approach should be used to address “risk” perception and awareness, ensure treatment adherence, and improve access to prevention services and management for both HIV and STIs. Dissemination of this unified message via patient-centered language offers a powerful opportunity to destigmatize HIV and STIs and promote engagement in care.

AUTHOR ACKNOWLEDGEMENT

All authors contributed to manuscript creation.

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