BRISBANE, Australia – The risk of sexual Transmission of HIV with Viral loads of less than 1,000 copies per mL was almost zero, according to a meta-analysis and systematic review.

In eight studies involving 7,762 serodiscordant couples across 25 countries, there were two cases of possible transmission among patients who had detectable viral loads that were under that threshold, reported Lara Vojnov, PhD, of the World Health Organization in Geneva, in a presentation at the International AIDS Society Conference on HIV Science (IAS). The findings were simultaneously published in The Lancet.

In three studies, there was no HIV transmission when the partner living with HIV had a viral load less than 200 copies per mL, according to Vojnov and colleagues. And across four prospective studies, 323 transmissions occurred, but none of the transmissions occurred when infected partners were considered to have stably suppressed HIV, they said.

“Among all studies there were 2 cases of transmission when the index patient’s most recent viral load was less than 1000 copies per mL,” Vojnov’s group wrote. “However, interpretation of both cases was complicated by long intervals between the transmission date and the most recent index viral load result.”

“These data provide a powerful opportunity to destigmatize HIV and promote adherence to anti-retroviral therapy through dissemination of this positive public health message,” they stated. “These findings can also promote access to viral load testing in resource-limited settings for all people living with HIV by facilitating uptake of alternative sample types and technologies.”

However, the researchers emphasized that “these messages and results do not apply to transmission from mother to child. Because vertical transmission can occur during pregnancy, during childbirth, or through breastfeeding, the duration and intensity of exposure to viraemia is considerably higher than that of sexual transmission. There are also no data on risk of transmission through sharing of injection drug use equipment at varying levels of viraemia.”

The study coincided with a WHO policy brief, which addresses the issue of vertical mother-child transmission, stating that “[a]vailable evidence suggests that if a mother living with HIV is taking antiretroviral therapy and maintains a suppressed viral load during pregnancy, delivery and breastfeeding, the risk of vertical HIV transmission can be as low as

Vojnov’s group also noted that “[l]ow-level viraemia could have important health implications for individual patients; however, these outcomes have not been thoroughly studied in the context of current, optimal integrase inhibitor-based antiretroviral therapy. An undetectable viral load should be the ultimate goal for clinical management of all people living with HIV on antiretroviral therapy.”

In an accompanying comment, Linda-Gail Bekker, MBChB, of Desmond Tutu Health Foundation in Cape Town, South Africa, and colleagues highlighted the lack of data on transmission through shared needles. “This review underpins how people who use and inject drugs are so often left behind,” they wrote. “No evidence for viral load levels and the risk of parenteral HIV transmission was provided because in most instances people who use and inject drugs were actively excluded from or not included in these clinical studies.”

Bekker’s group said that the findings offer “strong support for the global undetectable equals untransmittable (U=U) campaign,” and that it’s “important to have strong clinical evidence that indeed HIV viral loads of less than 1000 copies per mL in an individual on antiretroviral therapy does mean that such an individual is no longer infectious to sexual partners. The evidence can be confidently summed up in the message that U=U.”

Bruce Richman, JD, of the Prevention Access Campaign, said in a statement that the “WHO clarification that an undetectable viral load can be confirmed by any WHO-approved test, is a game-changer for health equity, particularly in lower-income countries where plasma-based tests are not cost-effective and scalable. When the WHO’s new brief is translated from policy to implementation, millions more people living with HIV will have the assurance that they’re staying healthy and can’t pass on HIV.”

In a press statement, study co-author Laura Broyles, MD, of the Global Health Impact Group in Atlanta, also emphasized that the findings should “promote the expansion of alternative viral load testing modalities that are more feasible in resource-limited settings. Improving access to routine viral load testing could ultimately help people with HIV live healthier lives and reduce transmission of the virus.”

Vojnov and colleagues conducted the study with data from January 2010 to November 2022. “Studies were included if they pertained to sexual transmission between serodiscordant couples at various levels of viraemia, the science behind undetectable=untransmittable, or the public health impact of low-level viraemia,” they wrote.

A study limitation was the fact that some of the data “were imprecise due to variations across the studies in the definitions of ‘low viral load’, and in the timing and frequency of viral load testing and patient follow-up,” the authors explained.