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Consequences of low-level viremia among women with HIV in the United States

Presenter: Amalia Aldredge, MD, Infectious Diseases Fellow, Emory University, Atlanta, GA.


Levels of baseline viral suppression predicted virologic failure risk among women in the Women’s Interagency HIV Study taking antiretroviral therapy who were followed for 5 years, according to Amalia Aldredge, MD, Infectious Diseases Fellow, Emory University, Atlanta, GA, United States. While low levels of viremia are common in HIV patients, Aldredge said in an ID Week 2023 oral presentation, there are no clinical guidelines on counselling and management for low levels of viremia.

While viral loads above 200 cells/mL are considered viral failure, low-level viremia, with viral loads of up to 199 cells/mL, occurs in about a third of people with HIV taking antiretroviral therapy and has been associated with virologic failure risk, resistance, and inflammation and may increase risk of non-AIDS comorbidities, Aldredge said. Even though HIV pathogenesis, treatment response, and non-AIDS comorbidity risk are known to be sex-differential, women have been underrepresented in major studies, which have been conducted in majority-male populations. Increased cumulative HIV viral loads (virologic copy-years), she added, are associated with non-AIDS comorbidities, particularly in women.

“I think of copy-years as being akin to pack-years of smoking,” Aldredge said, adding, “We don’t know the contribution from low-level viremia.” The study aim was to examine the relationship between low-level viremia and time to virologic failure and to multimorbidity.

Aldredge and colleagues included women with HIV enrolled in the Women’s Interagency HIV Study between 2003 and 2020. All had received antiretroviral therapy for at least 1 year and had at least 2 consecutive HIV-1 viral loads less than 200 cells/mL. Aldredge noted that low-level viremia follows different patterns, with some persistent and others intermittent (known as “blips”). Investigators categorized women using 4 consecutive viral load measurements in a virologic categorization period and then followed them for outcomes assessment. The categories were:

  • Virologic suppression (viral load undetectable at all visits)
  • Intermittent low-level viremia (viral load detectable up to 199 cells/mL at nonconsecutive visits)
  • Persistent low-level viremia (viral load detectable up to 199 cells/mL at ≥ 2 consecutive visits)
  • Virologic failure (any viral load ≥ 200 cells/mL).

The associations of virologic category with time to incident virologic failure and multimorbidity (defined as ≥ 2 of 5 non-AIDS comorbidity components [hypertension, dyslipidemia, diabetes, cardiovascular disease, kidney disease]) were estimated using adjusted Cox proportional hazards models.

Among 1,598 women included (median age 47 years), 64% were Black and 21% were Hispanic. The median CD4 count was 652 cells/µL, and the rates of at least 95% adherence with antiretroviral therapy were reported at 87% overall, 90% in those with viral suppression, 86% in those with intermittent low-level viremia, 86% in those with with persistent low-level viremia, and 76% in those with with virologic failure. The study analysis did not include the 275 (17%) women who had virologic failure during the virologic categorization period.

Over a period of 18 months, viral suppression occurred in 58% of patients (n = 933), intermittent low-level viremia in 19% (n = 295), and persistent low-level viremia in 6% (n = 95). Underscoring that intermittent or persistent low-level viremia occurred in 25% of participants, Aldredge noted that compared with viral suppression, the adjusted hazard ratio for incident virologic failure was 1.89 (95% CI 1.45–2.47) for those with intermittent low-level viremia and 2.31 (1.53–3.47) for those with persistent low-level viremia. After excluding 543 women with baseline multimorbidity, the adjusted hazard ratio for incident multimorbidity was higher for women with persistent low-level viremia at 1.61 (0.93–2.82) and lower for those with intermittent low-level viremia (0.84 [0.56–1.26]).

Compared with viral suppression, Aldredge said, intermittent and persistent low-level viremia were associated with increased risk of virologic failure. After covariate adjustment, persistent low-level viremia was associated with a trend toward increased multimorbidity risk. Aldredge observed that the low-level viremia rate of 25% in women is lower than the rate found in prior studies in men. She and colleagues are now evaluating the impact of sex and gender on low-level viremia and its consequences. “But ultimately, we need further research to mitigate the adverse consequences of low-level viremia,” she concluded.

Dr. Aldredge had no conflicts to disclose.

References

Crespo-Bermejo C, de Arellano ER, Lara-Aguilar V, et al. Persistent low-level viremia in persons living with HIV undertreatment: an unresolved status. Virulence 2021; 12(1):2919–2931. doi:10.1080/21505594.2021.2004743

Elvstam O, Malmborn K, Elén S, et al. Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort. Clin Infect Dis 2023; 76(1):25–31. doi:10.1093/cid/ciac762

Taramasso L, Magnasco L, Bruzzone B, et al. How relevant is the HIV low level viremia and how is its management changing in the era of modern ART? A large cohort analysis. J Clin Virol 2020; 123:104255. doi:10.1016/j.jcv.2019.104255

Morton ZP, Mehta CC, Wang T, et al. Cumulative HIV-1 viremia is associated with increased risk of multimorbidity among U.S. women living with HIV, 1997–2019. Open Forum Infect Dis. Published online December 28, 2022:ofac702. doi:10.1093/ofid/ofac702

Collins LF, Sheth AN, Mehta CC, et al. Incident non-AIDS comorbidity burden among women with or at risk for human immunodeficiency virus in the United States. Clin Infect Dis 2021; 73(7):e2059–e2069. doi:10.1093/cid/ciaa1928

Collins LF, Sheth AN, Mehta CC, et al. The prevalence and burden of non-AIDS comorbidities among women living with or at risk for human immunodeficiency virus infection in the United States. Clin Infect Dis 2021; 72(8):1301–1311. doi:10.1093/cid/ciaa204

Pond RA, Collins LF, Lahiri CD. Sex differences in non-AIDS comorbidities among people with human immunodeficiency virus. Open Forum Infect Dis 2021; 8(12):ofab558. doi:10.1093/ofid/ofab558

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