This Week in HIV Research: Unexpected Outcomes

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Normally, HIV treatment works. Normally, it also improves a person's CD4 count. But "normally" isn't always -- and as all of our studies this week can attest, counterintuitive outcomes sometimes occur. Our latest review of recently published research features attempts to describe and explain these results:

  • A patient-centered care model improves viral suppression -- despite only modestly affecting adherence.
  • Subpar immune responses occur nearly half the time among people who start HIV treatment with a CD4 count over 500.
  • Extreme drops in CD4 count occur very rarely in the face of viral suppression.
  • Vaccination alone may not be enough to protect HIV-positive people from hepatitis A exposure.

Read on to learn more about each of these findings. To beat HIV, you have to follow the science!


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Viral Suppression Improves Under Patient-Centered Care Model

A patient-centered care model significantly improved viral suppression rates, researchers reported in Clinical Infectious Diseases. This was especially true among African-American participants, whose viral suppression rate rose by 23%, from 63% to 78% of people in that group.

This was a demonstration project in which community pharmacists and HIV medical providers shared clinical information, identified treatment-related problems, and developed plans to overcome them. It was conducted at 10 project sites across the U.S., with 26 to 107 enrollees at each site, for a total of 765 participants, 43% of whom are African American. Adherence data – based on a Proportion of Days Covered (PDC) measure, i.e., whether prescriptions had been filled -- were analyzed for 421 people and viral suppression data for 649 persons.

Although the overall percentage of people who were adherent didn't change significantly, people who began the study with an especially low level of adherence (less than 50% PDC) did improve by a great deal -- from a mean of 28% PDC to a mean of 62%. Viral suppression increased from 75% overall at baseline to 86% overall at the end of the demonstration project, with particularly high gains seen among people with private insurance (up 31%), adults aged 25-34 (up 26%), African Americans (up 23%), and Ryan White care recipients (up 23%).

Participating pharmacists had received HIV-specific, as well as cultural competency training. They reviewed medication regimens and worked with clinicians to optimize treatment plans. This strategy may have resulted in more effective antiretroviral regimens, which in turn could explain the findings, study authors hypothesized. Improved retention in care among study participants could also have contributed to the results, they added.


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Poor Immune Recovery Common When Starting Treatment With Higher CD4 Count

At initial CD4 cell counts > 500 cells/mm3, 40% of participants saw little improvement in that count (≤ 50 cells/mm3 increase) after eight months on HIV treatment, a data analysis from the START trial published in AIDS showed.

START is a large randomized multi-country trial comparing immediate treatment after diagnosis to starting antiretroviral therapy only when CD4 cell counts drop to 350 cells/mm3. The data in the current study come from 1,884 participants in its immediate treatment arm.

Low CD4 recovery was more likely in men, in those with lower HIV RNA levels, lower CD4 cell counts at initial screening for study participation, and higher CD8 cell counts at baseline. It was also more common in African participants -- who were also more likely to be treated with one NNRTI + 2 NRTIs than those in the U.S., where treatment often includes one PI + 2 NRTIs.

Unlike other studies, age made no difference in the results, the researchers wrote. However, most of the cohort was younger than 45.

It is unclear whether a low CD4 cell recovery poses a mortality or morbidity risk to those with high counts to begin with, study authors noted, since too few clinical events occurred in the immediate treatment arm to give the study sufficient power to explore that question.


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Genetic Factors May Play Role in Extreme CD4 Drop Despite Viral Suppression

Genetic factors may play a role in unusual cases where a person's CD4 cell count drops steeply despite consistent viral suppression, a small study published in JCI Insight showed.

Researchers compared five people with such a CD4 decline (which researchers called extreme immune decline, EXID) to 15 more typical immunological non-responders and eight people who had a good immunological response to HIV treatment. After 192 weeks of treatment, those in the EXID group had lost a median of 157 CD4 cells/µl, in one case dropping to as low as 9 cells/µl. During that same period, non-responders gained a median of 193 cells/µl and responders 427 cells/µl.

EXID participants were from sub-Saharan Africa and the Middle East and had HIV clades other than B (the HIV version most common in North America and Europe). An autoimmune response that depletes CD4 cells and an altered inflammasome/caspase-1 activation, both influenced by genes, appear to be the two mechanisms contributing to EXID, study authors concluded.

Further research into this phenomenon may help develop treatments for immunological non-responders, according to a related press release.


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Immunoglobulin After Hep A Exposure Warranted for People With HIV, Even if Vaccinated

Six of the 11 people living with HIV who contracted the hepatitis A virus (HAV) during an acute outbreak had been previously vaccinated against HAV, the Tennessee Department of Health reported in Morbidity and Mortality Weekly Report.

About 90% of the general population is already protected against hep A after the first dose in a 2- or 3-shot series, but immunity is not developed to the same degree in people living with HIV. Depending on CD4 cell count and HIV viral load when the first vaccine dose is given, those with HIV may take longer to achieve hepatitis seroconversion and the vaccine's effect may taper off sooner than in people with intact immune systems, the researchers write. Among the six people in the outbreak who had been vaccinated, four had been only partially vaccinated; two had received the full course of hep A vaccination; and one received hepatitis post-exposure prophylaxis after an initial and subsequent exposure to HAV.

Study authors recommended that health care providers consider giving immunoglobulin prophylactically after a person living with HIV has a high-risk exposure to hepatitis A independent of that person's vaccination history.