HIV confab highlights SF research

  • by Liz Highleyman, BAR Contributor
  • Thursday March 16, 2023
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Dr. Annie Luetkemeyer of UCSF presented research at the recent Conference on Retroviruses and Opportunistic Infections in Seattle. Photo: Liz Highleyman
Dr. Annie Luetkemeyer of UCSF presented research at the recent Conference on Retroviruses and Opportunistic Infections in Seattle. Photo: Liz Highleyman

The recent Conference on Retroviruses and Opportunistic Infections featured the work of San Francisco experts, including studies of long-acting injectable HIV treatment and antibiotics to prevent sexually transmitted infections. Highlights from CROI were discussed at the March 9 meeting of the San Francisco Getting to Zero consortium.

Though primarily an HIV meeting, CROI, which took place last month in Seattle, also includes breaking research on new infectious diseases, which this year included COVID-19 and mpox. Mpox has declined dramatically in the Bay Area and across the country, but it still poses a threat to vulnerable people, including those with untreated HIV.

At the conference, Dr. Chloe Orkin of Queen Mary University of London presented results from an analysis of nearly 400 HIV-positive mpox patients in 19 countries, mostly gay men, who had a CD4 T-cell count below 350. Many developed severe manifestations, including extensive lesions, tissue death, and lung involvement. No one with a CD4 count above 200 died, but mortality reached 27% for those with a count below 100.

The presentation of mpox is "very starkly different" among HIV-positive people with advanced immune suppression, Orkin said at a CROI press briefing. She and her colleagues argue that mpox should be considered an AIDS-defining opportunistic infection.

In San Francisco, "we saw some really extreme mpox cases, mainly in people with low T-cell counts," Getting to Zero co-chair Dr. Diane Havlir of UCSF said at the recap meeting. "People did not get [severe mpox] if they were taking HIV treatment and had viral suppression. We absolutely can't let our guard down."

HIV vaccine study

Dr. Susan Buchbinder of UCSF and the San Francisco Department of Public Health presented further details about the latest HIV vaccine failure at CROI.

As the Bay Area Reporter previously reported, the Mosaico trial, which included 30 participants in San Francisco, was halted ahead of schedule in January after interim results showed that a combination vaccine regimen did not provide protection. The HIV incidence rate was 4.1 cases per 100 person-years in both the vaccine and placebo groups. Researchers are now focusing on broadly neutralizing antibodies and more sophisticated vaccine approaches, some of which use the same mRNA technology as COVID vaccines. "There's a really robust pipeline" of new prevention strategies, Buchbinder said.


Doxycycline post-exposure prophylaxis for STI prevention, dubbed doxy-PEP, was among the biggest news at the CROI.

As previously reported, the DoxyPEP study enrolled more than 500 gay and bisexual men and transgender women in San Francisco and Seattle who were either living with HIV or taking PrEP pills. Participants who were randomly assigned to take a single oral dose of doxycycline within 72 hours after sex had about a 65% lower likelihood of being diagnosed with chlamydia, gonorrhea, or syphilis per quarter.

One concern with this approach is that overuse of antibiotics could potentially lead to drug resistance. Dr. Annie Luetkemeyer of UCSF presented follow-up results showing only modest changes in gonorrhea and staph drug resistance in people who used doxycycline for STI prevention.

"We didn't see a marked increase in antimicrobial resistance associated with doxy-PEP use," she told reporters. "We need larger and longer studies of what happens to common bugs," but this must be weighed against the benefits of a substantial reduction in STIs, she noted.

Dr. Jean-Michel Molina of the University of Paris Cité presented findings from another study that evaluated doxycycline PEP plus a vaccine to prevent gonorrhea. The Bexsero meningococcal B vaccine is approved for the prevention of meningitis caused by related bacteria, but it also offers protection against gonorrhea.

The DoxyVAC study included 502 gay and bisexual men on PrEP who had an STI within the past year. They were randomly assigned to receive doxy-PEP or standard care and separately randomized to receive the vaccine or not. Over nine months of follow-up, doxy-PEP and the vaccine each reduced the risk of gonorrhea by 51%, and men who received both had additive protection.

"Even a vaccine with moderate effectiveness could have a big impact," Molina said. "It could reduce the overall burden of gonorrhea, which is becoming more and more resistant."

Unfortunately, doxy-PEP did not work so well for cisgender women. The dPEP Kenya trial enrolled 449 young cisgender women on PrEP. Here too, they were randomized to take doxycycline within 72 hours after sex or received standard care. STI incidence was high, at 27%, with no significant difference between the two groups. Presenter Jenell Stewart, a doctor of osteopathic medicine at the Hennepin Healthcare Research Institute in Minneapolis, said the lack of protection could be attributable to anatomical differences between women and men, poor adherence, or a high level of pre-existing drug resistance.

Another presenter said the results were discouraging.

"The results from the study are deeply disappointing, and we are committed to understanding why doxycycline PEP did not work in this population and also determining the next steps for how to identify prevention tools that will work for and can be used by women," stated principal investigator Dr. Elizabeth Bukusi of the Kenya Medical Research Institute.

DPH is already rolling out doxy-PEP for gay and bi men and transgender women in San Francisco. Asked whether the federal Centers for Disease Control and Prevention should recommend doxy-PEP, Luetkemeyer said, "I think there's enough data out there, and people are looking for guidance. I think it's time to weigh in now as we continue to learn more."

In a statement commenting on the study findings, Dr. Leandro Mena, director of CDC's Division of STD Prevention, said, "These and other data will be vital to our ongoing efforts to ensure CDC's STI treatment and prevention guidance and the Advisory Committee on Immunization Practices vaccine recommendations are aligned with the latest science."

HIV treatment

People living with HIV in San Francisco generally receive good care, but disparities persist. At CROI, DPH researchers presented findings from two studies looking at treatment and PrEP use among approximately 500 people who inject drugs (PWID) in San Francisco based on data from the recently completed National HIV Behavioral Surveillance survey.

Despite an overall decrease in new HIV diagnoses in the city between 2018 and 2022, new cases among PWID jumped by 33%; this group now accounts for 27% of newly diagnosed people. Although 80% of PWID living with HIV in San Francisco are diagnosed, 73% are on antiretroviral treatment and just 52% have an undetectable viral load. Only people experiencing homelessness (an overlapping group) have a lower viral suppression rate, at 27%, according to DPH's 2021 HIV epidemiology annual report; this compares with an overall viral suppression rate of 72%. What's more, just 55% of PWID were aware of PrEP (versus 98% of gay men) and only 1.5% were using it in 2022 (compared with 65% of gay men).

"San Francisco is not on course to get to zero HIV infections among PWID," the researchers concluded. "PWID-sensitive and focused programs are needed to increase HIV testing overall, sustain retention in care, and address stigma if San Francisco is to end the epidemic for all."

Long-acting injectable therapy may be one way to improve outcomes among people who use drugs, people with unstable housing, and others who struggle to stay engaged with traditional HIV care.

The federal Food and Drug Administration approved the first injectable antiretroviral regimen, Cabenuva (cabotegravir plus rilpivirine), in 2021, but only for people with an undetectable viral load who wish to switch to monthly or every-other-month treatment. But this may also be a feasible option for people who have been unable to achieve and maintain viral suppression due to challenges with adherence.

The Ward 86 HIV clinic at Zuckerberg San Francisco General Hospital and Trauma Center is now pioneering this approach with SPLASH, the Special Program on Long-Acting Antiretrovirals to Stop HIV. The program offers intensive support, including case managers, phone or text reminders, and street-based nursing services. Ward 86 medical director Dr. Monica Gandhi said that if a person misses an injection, clinic staff call them and even go looking for them in the community.

Gandhi and her team evaluated outcomes among 133 people who switched to Cabenuva from oral antiretrovirals. Two-thirds were homeless or lacked stable housing, a majority reported substance use, and many had mental health issues. Among the 76 people who already had an undetectable viral load, all maintained viral suppression after switching to the injections. The more exciting finding was that all but two people who started the injections with a detectable viral load were able to get their HIV under control. These response rates were "equivalent to those in clinical trials," Gandhi told the B.A.R.

Use of Cabenuva for people without viral suppression goes beyond the FDA-approved indication, and it might not be an option for those who don't get the same level of intensive support. But for some, it could offer a lifeline.

"For those of us treating HIV on a daily basis, we know that some patients have challenges taking pills, including substance use, housing and food insecurity, and stigma," Gandhi said. "If used creatively and used boldly, long-acting antiretroviral treatment could really make a dent in the epidemic."

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