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Higher Mortality Risk Linked to Mental Illness in Persons Living With HIV


In this study from Cape Town, South Africa, patients with comorbid HIV and a history of mental illness had an increased risk of mortality from all causes.

Overall and multivariable analyses conducted among HIV-positive patients on antiretroviral therapy (ART) living in Cape Town, South Africa, showed an association between increased risk of mortality and having a history of mental illness, reports The Lancet Global Health.

The variables adjusted for in both analyses were age, sex, treatment program, and year of ART initiation. Multivariable analysis also accounted for CD4 count and World Health Organization (WHO) clinical stage at ART initiation, retention in HIV care with or without viral load suppression (VLS), and loss to follow-up (LTFU).

VLS was classified as a viral load below 1000 copies/mL, nonsuppressed viral load (NVL) as a viral load of 1000 copies/mL or greater, and LTFU as being beyond 180 days late for a clinic visit at data cutoff.

“Our study is one of a few to quantify mortality associated with mental illness in HIV-positive populations of low-income and middle-income countries and, to our knowledge, the first to do so in South Africa, where the HIV-positive population accounts for 20% of all cases globally,” the authors noted. There is a scarcity of data on mental health–related mortality among people with HIV, they added, despite the fact that these disorders are known to be prevalent among this patient population and linked to poor ART adherence.

The 58,664 patients included in their studies were a median (interquartile range [IQR]) of 33 (28-40) years old and receiving ART between January 1, 2004, and December 31, 2017, in Cape Town. ART program data, from Gugulethu Community Health Clinic, Tygerberg Academic Hospital, and the Khayelitsha ART programme; mental health treatment records; and mortality data from the South African National Population Register were linked for analysis. Just 1 instance of receiving psychiatric medication (antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, or psychostimulants) or being hospitalized for a mental disorder constituted having a history of mental illness.

Of the total patients followed for a median 4.3 (IQR, 2.1-6.4) years, 5.0% (n = 2927) had a history of mental illness. Compared with patients with no history of mental illness, patients with comorbid HIV/mental illness had increased risk of mortality on 3 fronts:

  • All causes: adjusted HR (aHR), 2.98 (95% CI, 2.69-3.30)
  • Natural causes: aHR, 3.00 (95% CI, 2.69-3.36)
  • Unnatural causes: aHR, 2.10 (95% CI, 1.27-3.49)

A total of 6.8% of patients died during follow-up.

Multivariable analysis also produced a higher risk, with an aHR of 2.73 (95% CI, 2.73-3.02).

A third adjustment for results, using a multistate model—that accounted for age, sex, year of ART initiation, cumulative time with NVL, and WHO clinical stage and CD4 cell count at ART initiation—showed an elevated mortality risk on 3 additional fronts:

  • Patients retained in care with VLS: aHR, 3.43 (95% CI, 2.83-4.15)
  • Patients retained in care with NVL: aHR, 2.74 (95% CI, 2.32-3.24)
  • Patients LTFU: aHR, 2.12 (95% CI, 1.78-2.53)

HIV RNA viral load was measured at several time points: 4 to 6 and 12 months after starting ART and annually thereafter.

Additionally, persons with HIV and a history of mental illness were linked to an increased risk of viral rebound:

  • From VLS to NVL: aHR, 1.50 (95% CI, 1.32-1.69)
  • People with VLS LTFU: aHR, 1.19 (95% CI, 1.06-1.34)

Differences in probability were also seen at the post–ART initiation 10-year mark when comparing patients with and without mental illness, especially for death:

  1. With mental illness:
    1. Death: 32.0% (95% CI, 28.9%-35.1%)
    2. LTFU: 34.0% (95% CI, 30.8%-37.1%)
    3. Retention in care with VLS: 28.9% (95% CI, 26.2%-31.7%)
    4. Retention with NVL: 5.1% (95% CI, 3.5%-6.7%)
  2. No mental illness:
    1. Death: 13.4% (95% CI, 12.9%-13.9%)
    2. LTFU: 45.3% (95% CI, 44.6%-46.0%)
    3. Retention in care with VLS: 38.0% (95% CI, 37.4%-38.7%)
    4. Retention with NVL: 3.2% (95% CI, 2.9%-3.5%)

“Excess mortality among people with a history of mental illness occurred independently of HIV treatment success,” the authors concluded. “Interventions to reduce excess mortality should address the complex physical and mental health-care needs of people living with HIV and mental illness.”

They also note that their findings echo those of previous studies linking mental illness with “excess mortality” in persons living with HIV, especially the finding that ART adherence drops.

However, they caution interpretation and generalization due to the influence of confounders that include physical comorbidities and socioeconomic status.


Haas AD, Ruffieux Y, van den Heuvel LL, et al. Excess mortality associated with mental illness in people living with HIV in Cape Town, South Africa: a cohort study using electronic health records. Lancet Glob Health. 2020;8(10):e1326-e1334. doi:10.1016/S2214-109X(20)30279-5

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