51成人动漫

SAN FRANCISCO -- A San Francisco man was infected with a partially resistant strain of HIV despite consistent use of Truvada (tenofovir DF/emtricitabine) for pre-exposure prophylaxis (PrEP), a researcher said here.

After a year on PrEP with apparently good adherence according to blood and hair sample tests, the young man was infected with an HIV strain that was resistant to emtricitabine, but still susceptible to tenofovir, reported Stephanie Cohen, MD, of the San Francisco Department of Public Health.

This is the sixth known case of HIV infection despite a high level of adherence, the authors said in a at the annual IDWeek meeting, with joint sponsorship by the Infectious Diseases Society of America (IDSA), the (HIVMA), the (SHEA), and the (PIDS).

"We've always said that PrEP is not 100% efficacious," Charlene Flash, MD, of Baylor College of Medicine in Houston, who was not involved with the case report, told 51成人动漫. "So although it's important for us to evaluate the parameters of what happened in each individual case, it's an important reminder that PrEP is not a golden bullet. It's just one element in our prevention toolkit."

The FDA approved Truvada for HIV prevention in 2012 based on data from the iPrEx trial, which showed that once-daily Truvada reduced the risk of HIV infection by 92% among mostly gay and bisexual men with blood drug levels indicating consistent use. Across several other studies and demonstration projects, no one who took Truvada at least four times a week has become infected.

However, a handful of cases of apparent or confirmed PrEP failure in real-world use have been reported at scientific conferences and in the medical literature.

In 2016, that a man who used PrEP consistently was infected with an HIV strain that was resistant to both tenofovir and emtricitabine. A similar case was reported in New York City later that year. In 2017, researchers from Amsterdam reported the first case of PrEP breakthrough involving drug-susceptible HIV.

Another probable case from North Carolina was presented at a conference earlier this year. That case was the first to measure drug levels in hair samples to assess adherence over time. This technique showed that the man had adequate tenofovir levels during the three months prior to testing positive for HIV, but because he had short hair this was as far back as the tests could go.

The latest case involves a 21-year-old young Latino man who reported having sex with men and transgender and non-transgender women. He tested negative for HIV antibodies and HIV RNA at San Francisco's main STI clinic. He was prescribed a 30-day supply of daily Truvada with two refills and asked to return in 3 months for follow-up monitoring. He again tested negative for HIV at 3, 6, and 10 months after PrEP initiation.

At his 13-month visit, a rapid HIV antibody test was negative and his PrEP prescription was renewed. But 5 days later his HIV RNA test came back positive, with a viral load of 559 copies/mL.

The man reported excellent adherence to PrEP and drug level tests supported his self-reports. Blood plasma measurement showed that he had adequate levels of tenofovir and emtricitabine prior to this clinic visit, and dried blood spot testing indicated good adherence over the preceding 6 weeks. Because he had longer hair than the North Carolina man, hair segment tests were able to show adequate levels of tenofovir going back 6 months.

Genotypic and phenotypic testing showed that the man's HIV was resistant to emtricitabine, with the L74V, L100I, M184V, and K103N mutations. However, his virus remained susceptible to tenofovir and did not have the K65R mutation. The genetic diversity of his virus population suggested he had acute infection, probably acquired within the previous few weeks, according to the researchers.

The man was immediately notified and started a complete antiretroviral regimen consisting of tenofovir alafenamide, emtricitabine, dolutegravir (Tivicay), and ritonavir-boosted darunavir (Prezista). In addition, one of his sex partners was found to be HIV positive with the same viral genotype and an HIV RNA level of 15,000 copies/mL, and he was re-linked to care.

Based on these findings, the researchers concluded that HIV acquisition can occur in a person taking Truvada PrEP when the virus is resistant to emtricitabine, even if adherence is high and it remains susceptible to tenofovir.

"Individuals taking PrEP and health care providers should be aware that PrEP failure is very rare, but not impossible, even with consistent adherence," they wrote.

Robert Grant, MD, of the UCSF Gladstone Institutes, the lead investigator for the iPrEx trial, put the latest case into perspective, asking why the media puts so much emphasis on occasional PrEP failures.

"HIV infections during PrEP use are extremely rare," Grant told 51成人动漫. "There are only a few cases reported worldwide after hundreds of thousands of people have used PrEP and tens of thousands of HIV infections have been prevented. Almost all people who use PrEP stay free of HIV, and a handful of others are diagnosed early and promptly and successfully treated."

Cohen emphasized that HIV breakthroughs while taking PrEP consistently are not a significant contributor to new infections.

"By far the most common reason for PrEP to not work is because it isn't used," she told 51成人动漫. "In other words, our biggest challenge in HIV prevention is not figuring out why in these extremely rare circumstances PrEP is ineffective, but rather how can we make sure those who can benefit from PrEP know about it? How can we make it as acceptable, accessible and affordable as possible? And how do we support individuals who choose to take PrEP so that they can stay on it throughout periods of risk?"

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