Combinations containing TAF and cobicistat linked to physical depression symptoms in women with HIV


Women with HIV taking antiretroviral combinations containing tenofovir alafenamide (TAF) and a cobicistat-boosted protease inhibitor or integrase inhibitor were more likely to experience numerous physical symptoms of depression than women taking other antiretroviral regimens, the Women’s Interagency HIV Study reported at the 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023) in Seattle on Tuesday.

The study investigators say their findings suggest that doctors need to look at drug combinations rather than individual antiretrovirals when considering whether HIV medication might be causing or contributing to the physical symptoms of depression.

Depression manifests in several ways. Non-physical symptoms such as sadness, hopelessness, despair, loss of libido, lack of pleasure and suicidal thoughts are often accompanied by physical symptoms including sleep disturbance, tiredness, changes in appetite, weight gain or loss, aches and pains, or sexual dysfunction.



A mental health problem causing long-lasting low mood that interferes with everyday life.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Physical symptoms accompanying depression are more common in women than men and may be confused with symptoms of menopause or side effects of antiretroviral treatment in women with HIV. Some antiretroviral drugs have been associated with depression, especially in people who've had depression in the past, but there is no gender-specific information about the impact of antiretroviral treatment on depressive symptoms in women with HIV.

Some antiretroviral drugs have been associated with depression but it can prove challenging for clinicians to identify which agents might be contributing to depression and whether antiretroviral drugs are exacerbating physical or non-physical symptoms of depression. Identifying the role of specific drugs or combinations in depression is important for improving the management of depression, which is a common mental health problem in people with HIV.

Women’s Interagency HIV Study (WIHS) researchers investigated the contribution of antiretroviral drugs in combination to physical and non-physical symptoms of depression in women with HIV.

This cohort study follows women with HIV in the United States. Participants are questioned about depression at each clinic visit using a standardised questionnaire. In this analysis, WIHS investigators looked at depressive symptoms in 1538 women who had attended clinic visits at least twice since 2014.

Participants had a mean age of 49, 72% were Black and 14% were Hispanic and just over a quarter had a viral load above 50 copies/ml (27%).

The majority of women were taking tenofovir disoproxil fumarate (TDF) (54%) and 20% were taking tenofovir alafenamide (TAF). Just under half were taking an integrase inhibitor (49%), a third were taking a non-nucleoside reverse transcriptase inhibitor (33%) and 31% were taking a protease inhibitor.

The investigators divided participants into three groups: those with high depression scores at a majority of clinic visits (459 participants), those with low depression scores at the majority of visits (500 participants) and those with no depressive symptoms at any visit (579 participants).

Compared to women with no depression, women with high depression scores were significantly less likely to have completed high school, significantly more likely to have a household income of $12,000 a year or less, and significantly more likely to report that they smoked, and had recently used marijuana or crack cocaine, cocaine or heroin.

The researchers analysed the association between antiretroviral drug exposure during the follow-up period and depression physical symptom scores. Three drug combinations were found to be associated with high physical symptom scores in the high depression score group:

When cobicistat-boosted darunavir or elvitegravir were combined with tenofovir disoproxil fumarate (TDF), the original formulation of tenofovir, there was no significant association between these combinations and a high physical symptom score in the high depression score group.

Women taking the following two combinations had significantly lower physical symptom scores in the high depression score group:

In the low-depression score and no-depression groups, no drug combination was associated with higher or lower rates of physical symptoms of depression.

No drug combination was associated with a higher rate of non-physical symptoms of depression in any group.  

No other combinations were associated with an increased risk of depressive symptoms.


Parra-Rodriguez L et al. Effect of common antiretroviral combinations on depressive symptoms in women with HIV. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 469, 2023.

View the abstract on the conference website.