The question of efavirenz

Efavirenz (Sustiva) has been particularly suspected of causing long-term depression and sleep disturbance in a minority of people taking it that persists beyond the well-documented central nervous system (CNS) side-effects commonly seen in the first month on therapy. Some studies, such as one in Australia (Kelly), found that up to 40% of patients on the drug continued to report CNS side-effects during long-term follow-up, and that these persisted beyond 18 months in 16% of patients.

Allin and colleagues from King’s College Hospital in London reported on a small group of six patients who had been referred over a two-year period from a single London hospital with acute severe psychiatric symptoms including suicidal ideation out of a total of 200 patients who had started medication with efavirenz. Suicide was out of proportion to the depressed mood and inner feelings of tension that were also reported and was attempted in two cases, with homicidal ideation additionally present in one of the six. All symptoms resolved when efavirenz was withdrawn. Four of the six patients had a prior psychiatric history but two did not.

Other studies however, (e.g. Blanch) have found that CNS side effects fade away to below the level of statistical significance in all but a small minority of patients. If you are virologically suppressed on efavirenz but suspect that it may be causing symptoms like depression, anxiety, bad dreams or sleep disturbance, it may be possible to switch to either nevirapine or PI-based therapy. Many HIV physicians avoid giving efavirenz to people with histories of psychiatric illness.

The stigma of lipodystrophy

One of the ironies of HAART was that as soon as combination therapy became really effective, it started producing facial and bodily fat redistribution and shape changes that made some people look sicker or more distinctive than they ever had before.

The first paper to examine the psychological effects of lipodystrophy was written in 2000 (Collins). Qualitative data were collected from 33 individuals, including 14 heterosexual women and 19 gay men. Average age was 39 years, with a range of 29 to 56 years.

Body image was generally poor, with some respondents describing themselves as "grotesque," "deformed," or "damaged goods." Responses included: "I've basically decided that I will be unattractive to a potential partner. I find myself concentrating on the outside and choosing to overlook what might be attractive on the inside."

Self-esteem was also affected, with individuals describing feeling "unloved and unlovable." One said: "Like all gay men, I relied (perhaps too heavily) on physical attractiveness to define me and bolster my self-esteem."

Many claimed that they had been able previously to cope with HIV and still feel good about themselves but that now, with the body changes, coping has become increasingly difficult.

Effects on social relations related mainly to social withdrawal. Responses here included: "I don't really go out in public much anymore unless it is to the market, or occasionally to the movies -- in the dark. Strangers stare. Children point." "I feel I should go to the gym to do something about this, but I am too embarrassed to be seen in my gym clothes."

Sexual relations were frequently affected by the general feeling of unattractiveness. One person described his body changes as being "cruise suicide." Another said: "I feel self-conscious in public, sexually unattractive, so don't try to stimulate an already reduced libido." From a woman whose husband is negative and who gained 22.5 kg (50 lb) within months of starting HAART: "He now refuses to have sex with me... only as my body changed has the HIV become an issue in our love lives. Now, he is afraid of catching HIV. Perhaps he was in denial before."

There were other issues related to current relationships. A number of respondents said they were afraid their partners no longer found them attractive. One said: "My lover left me because, as he has no lipodystrophy and no viral load, my face was a constant reminder of the HIV he allowed himself to ignore."

Disclosure issues were a common theme, with comments including: "People in my community can tell I am HIV-positive from just looking at my face. It is like the old KS [Kaposi sarcoma] lesion on the nose." "It is no secret what this face means. I have been open about my [HIV] status, but I prefer to announce it myself. Not have it plastered across my face." "All my students and co-workers started to tell me 'how skinny I was.' In my thoughts, this meant 'how sick you are.'"

After an article was published in a local newspaper describing lipodystrophy, one man said it had likely "outed" him to his family after he had been able to hide his HIV from them for 15 years. While forced disclosure relates to a loss of control, other experiences threaten locus of control. Examples were "I feel my body changes are out of my control, and it is concurrent with feeling my life is out of control." "There seems so little I can do to prevent this or correct it. All my doctor tells me is to work out and is not even sure that can help."

Feelings of helplessness and of loss of control can lead to depression. Depression and demoralization were frequently expressed themes in the sample: "I feel constantly dejected." "I have thought about killing myself seriously. I guess what keeps me going is the hope of T20 [a new antiretroviral drug being developed]." "I used to be able to stay quite positive about the inconveniences, feeling that it was worth it to still be alive. Now, I am finding it hard to keep that attitude - I'm feeling really sick and tired of dealing with AIDS and sometimes wonder if it is worth it anymore. I used to keep up with all the research and developments, and now I just cannot muster the oomph to do it. How much this bad attitude re AIDS is connected to the poor body image and resulting poorer self-esteem I cannot say. I can say they are happening at the same time."

Not surprisingly, given this treatment-associated burden, when treatments were developed that ameliorated the appearance of lipodystrophy they were welcomed by patients and improved their mental health.

In one study (Moyle) 30 patients were randomised to two arms for immediate or deferred treatment with polylactic acid (New-Fill) to correct the appearance of facial wasting. Patients provided self-assessment of appearance on a visual analogue (VA) scale and a Hospital Anxiety and Depression assessment (HAD).

Patient VA assessments, anxiety and depression scores improved with treatment. At week 12, immediately-treated patients had significantly better VA scores (7 vs. 1, p<0.001) and 33% less anxiety (6 vs. 9 p=0.056) than Del patients. Benefits on VA and anxiety scores persisted through week 24. Depression scores fell in both groups by week 24, by two-thirds in the immediately treated group and by a half in the delayed treatment group.

References frequency of mental illness

Allin M et al. Frequency of serious psychiatric adverse events with efavirenz. Antiviral Therapy 8:L85. 2003

Anderson WJ, Weatherburn P. The needs of people with HIV in the UK: findings from a national survey. Int J STD AIDS 15(12): 793-796, 2004. “What do you Need?” survey can be downloaded from http://www.sigmaresearch.org/

Blanch J et al. Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. Journal of Acquired Immune Deficiency Syndromes 27(4): 336-343, 2001.

Cochran SD, Mays VM. Lifetime prevalence of suicide symptoms and affective disorders among men reporting same-sex sexual partners: results from NHANES III. Am J Public Health. 90: 573–578, 2000.

Cochran SD et al. Prevalence of non-medical drug use and dependence among homosexually active men and women in the US population. Addiction 99(8): 989-998, 2004.

Collins E. Psychosocial Impact of the Lipodystrophy Syndrome in HIV Infection. AIDS Reader 10(9): 546-551, 2000

Hooshyar D. Depression High Among HIV-Positive Patients: Rates Are More than Five Times Greater. AIDS Alert 19(3): 34, 2004.

Justice AC et al. Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study. AIDS 18: S49-S59, 2004.

Kelly M et al. Long-term follow-up of efavirenz usage in patients with HIV disease. 12^th Annual Conference of the Australasian Society for HIV Medicine, Melbourne, abstract 88, 2000.

Malanda S. Are we meeting the psychological needs of Black African HIV-positive individuals in London? Controlled study of referrals to a psychological medicine unit. AIDS Care 13(4): 413-419. 2001.

Moyle G. Polylactate (NewFill) Injections Subjectively and Objectively Improve Appearance and Reduce Anxiety and Depression Scores in HIV Positive Persons with Facial Lipoatrophy: A Randomised, Open Label, Immediate vs. Delayed Therapy Study. 42^nd ICAAC Conference, San Diego, abstract H-1934, September 27-30, 2002.

Paul JP et al. Suicide Attempts among Gay and Bisexual Men: Lifetime Prevalence and Antecedents. American Journal of Public Health 92(8), 2002.

Weatherburn P et al. Project Nasah: An investigation into the HIV treatment information and other needs of African people with HIV resident in England. Sigma Research, February 2003. Can be downloaded from http://www.nat.org.uk/documents/final.nasah.pdf

Weissman MM, Bland RC, Canino GJ, et al. Prevalence of suicide ideation and suicide attempts in nine countries. Psychol Med. 29: 9–17, 1999.