Low-level viremia in women is associated with viral failure, but next steps are unclear

Among people living with HIV in the U.S., low-level viremia (LLV) is common among women on antiretroviral therapy (ART) and is associated with a greater risk for virologic failure, a long-term study presented at IDWeek 2023 found. The findings also indicate that women living with HIV experience LLV slightly more than has been previously observed in men living with HIV. However, no clear relationship was seen between the development of LLV and incidence of non-AIDS comorbidities.

Although there is considerable data supporting a connection between LLV and a person’s long-term risk for viral failure, there remains considerable debate over the clinical relevance of LLV. These study results support the hypothesis that any degree of LLV—be it intermittent (i.e., a “blip”) or persistent—can increase virologic failure risk.

However, the results do not make it clear what to do about this potential risk. “Despite how common this is, there are no guidelines on how to counsel and manage people with low-level viremia,” observed study presenter Amalia Aldredge, M.D., of Emory University in Atlanta, Georgia.

Participant Characteristics

The primary analysis included 1,598 women who were enrolled in the Women’s Interagency HIV Study (WIHS) between 2003 and 2020; had been on guideline-based ART for at least a year; and had two consecutive viral load results below 200 copies/mL during the study’s eligibility period.

The WIHS cohort includes women living with or at risk of acquiring HIV across the U.S., though most study sites are located along the East Coast and Southeast. Study participant median age was 47 years; 64% of participants were Black and 22% were Latina. More than half of participants reported an annual household income below $12,000. Nearly half had a body mass index of 30 or higher.

Study Methods and Results

The eligibility period was followed by the virologic categorization period, which considered the participant’s subsequent four viral load measurements. Women were categorized into four groups:

• Maintained virologic suppression (no viral load above the lower limit of detection (LLD) during any study visit; 933 women)

• Intermittent LLV (i.e., “blips”—viral load between LLD and 200 copies/mL at two or more non-consecutive visits; 295 women)

• Persistent LLV (viral load between LLD and 200 copies/mL at two or more consecutive visits; 95 women),

• Virologic failure (viral load at or above 200 copies/mL at any visit; 275 women).

Participants with virologic failure were removed from the primary analysis, leaving data on 1,323 women.

At baseline, HIV characteristics were similar across the three groups included in the primary analysis. Overall, roughly equal proportions of participants were on integrase inhibitor-based, protease inhibitor-based, and non-nucleoside reverse transcriptase inhibitor-based (NNRTI) regimens.

While the majority of participants (58%) remained virally suppressed throughout the study’s five-plus years of follow-up, 18% of women experienced intermittent LLV and 6% experienced persistent LLV. “Both those with persistent and intermittent low-level viremia had an increased risk of viral failure,” explained Aldrege, even after adjusting for age, ART adherence, ART regimen, CD4 count, and race.

The researchers conducted a multimorbidity survival analysis among 780 study participants who experienced at least one of five categories of non-AIDS comorbidities (cardiovascular disease, chronic kidney disease, diabetes mellitus type 2, dyslipidemia, or hypertension) during follow-up. The analysis revealed a higher risk of such conditions among the persistent LLV group, which was attenuated after adjustment for several known risk factors. (The adjusted hazard ratio was 1.61, but with a 95% CI of 0.93 to 2.82.) Aldrege suggested that the trend may not have reached statistical significance due to the relatively small sample size.

Next Steps

The study showed a higher risk of virologic failure and a trend towards multimorbidity among women with LLV. But what does this mean in practice? “I don’t know what the next step is,” admitted Aldrige. “Until we know that, I don’t think we can do anything differently.” She called for further research, particularly in light of the continued development of ever-more-sensitive viral load assays that reduce the lower limit of detection.

Session moderator Maximo O. Brito, M.D., M.P.H., observed that with LLV under current HIV treatment guidelines, “there is no grounds for changing the treatment, so you are left with the anxiety of the patient, the anxiety of the physician.”

To reduce patients’ anxiety about viral blips, conference attendee Renslow Sherer, M.D., a professor of medicine at the University of Chicago Medical Center who spoke during the Q & A following Aldrege’s presentation, suggested sharing with patients a goal stated within U.S. treatment guidelines: maintaining a viral load below 200 copies/mL.

Study Information

Abstract 1025, “Consequences of Low-level Viremia Among Women with HIV in the United States,” was presented by Amalia Aldredge, M.D., at IDWeek 2023 in Boston, Massachusetts.

By Barbara Jungwirth