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Sexual healing
   Last updated: 27.10.04
Sexual dysfunction is affecting too many people with HIV, by Gus Cairns
An epidemic of sexual unhappiness?
The loss of sexual drive or desire, or problems achieving orgasm, can have a significant impact on an individual’s quality of life and feelings of self-worth, and may even contribute to emotional problems such as anxiety and depression. These problems – grouped together under one name, sexual dysfunction (SD) – can occur in anyone, but people living with HIV appear to be particularly affected.
A recent study1 by St Mary’s Hospital in west London found that 26% of their gay male patients with HIV (regardless of whether or not they were on HAART) reported low libido and the same percentage reported problems achieving an erection. When it came to individuals taking antiretrovirals, the proportion with erectile dysfunction (ED) increased to 48%, although the proportion of men experiencing loss of libido did not increase.
Compare this with 2% and 10%, respectively, for loss of libido and ED amongst a control group of HIV-negative gay men.
Dr Pepe Catalan, consultant psychiatrist at the Chelsea and Westminster Hospital in London, confirms that “sexual dysfunction is very common in people with HIV, even in patients not on antiretrovirals.” He says, “I see two or three patients a week here for it.”



How many, exactly?
The results of the St Mary’s study are not the highest-ever figures reported for sexual dysfunction in people with HIV. An earlier French study2 questioned 156 HIV-positive men on HAART about all aspects of sexual dysfunction – erectile function, ability to have an orgasm, sexual desire and satisfaction with sex. It found that 71% of them reported “some degree of sexual dysfunction since the beginning [of treatment]”. This compared with 18% of them reporting SD before testing HIV-positive and 32% after diagnosis but before initiating HAART.
Other studies have reported somewhat lower figures, however.
A US study3 found that 32% of gay men on HAART experienced “sexual dysfunction or loss of libido”. But this study excluded patients who had experienced SD before they started antiretrovirals and also relied on a review of case records to see if they had mentioned it to their regular HIV doctor. However, since the French study reported that 44% of the men with SD had never mentioned their problems to their regular physician, it is possible that the US study underestimated the prevalence of SD.
An Italian study from 20014 asked HIV-positive men on antiretrovirals about their inability to have or to sustain an erection. It found that 10% of patients on protease inhibitors (PIs) had ED compared with 7% on PI-sparing regimens. There was a higher rate seen (16%) in individuals taking indinavir, which, because it was the most frequently prescribed PI at the time, was taken by 70% of those with ED.


Desire, arousal and orgasm
As can be seen from the above studies, sexual dysfunction covers a range of different conditions. These may be broadly separated into three types:
  • Disorders of desire (not wanting it)

  • Disorders of arousal (not getting or sustaining erections, or in the case of women, vaginal dryness and/or not getting aroused)

  • Disorders of orgasm (not being able to achieve orgasm, or in the case of some men, achieving it too quickly)

Dr Catalan explains how he figures out which problems are which, and what may cause them. “You have to deconstruct the sexual dysfunction of the individual patient to find out whether they are complaining of erection problems, orgasm problems or loss of libido,” he says.
“If people are complaining of a loss of interest in sex – if they don’t masturbate or find they don’t think about sex at all – then I might suspect low testosterone levels and prescribe replacement therapy if it is low.
“But if people are still interested in sex but complaining about erection problems, I’ve given up measuring their testosterone, as it’s always turned out to be normal.
“Psychological factors are always part of sexual dysfunction, because, of course, once you’ve had one ‘failure’ you will be anticipating it each time. So it’s important to stress that it’s not all caused or cured by pills.
“A lot of my patients are gay men who’ve had a very active sex life when younger. They’ve used sex as ‘comfort eating’ and may have been used to having sex on recreational drugs. They come to me in their 40s and want to settle down, have a regular partner, start looking after themselves better. But sex in that context feels dull. They’ve ‘done’ sex! Here, more complex issues come into play, such as fear of intimacy and commitment.”


Does HAART cause sexual dysfunction?
It is still unclear which HIV medications cause SD, and to what degree, or whether the epidemic rates of SD in HIV-positive men are more to do with sex being problematic in general.
The US study found that the only two factors significantly associated with sexual dysfunction were the use of ritonavir and depression. People with one of these factors were 2.3 times more likely to report SD.
However this study relied on self-reported SD and, as the investigators comment themselves, “it is possible that decreased fear about infecting a potential sexual partner or an improved sense of well-being resulting from effective combination antiretroviral therapy may have caused patients to focus more on issues of sexual function.”
In the French study, although overall rates of sexual dysfunction were extremely high, no difference was seen in the rates reported among individuals who were taking PIs, had never taken PIs, or had taken them but switched to NNRTIs. However twice as many people on HAART experienced SD compared with those not on HAART.


Is it PIs or NRTIs?
In the Italian study, indinavir use was significantly implicated in ED. However this study also suggested that scientists may be fingering the wrong culprit when it comes to the class of antiretrovirals responsible. The researchers made measurements of the nerve function of a small subgroup of their patients and found that every single one had evidence of impaired electrical conductivity in the nerves serving the genital area. These are served by the very lowest (sacral) part of the spinal cord and may be particularly vulnerable to neuropathy. Nerves of the autonomic nervous system, which control arousal as opposed to sensation, could also be damaged. Could it be that the NRTI d-drugs are the culprits?
The recent St Mary’s study suggests that this is possible. It found that erectile dysfunction, as opposed to general sexual dysfunction, was doubled in the men on HAART, suggesting that there may a physiological link between HAART and the ability to have or sustain an erection. However, the study also found unusually high levels of the female sex hormone, oestradiol, in these men. Since most PIs and two of the NRTIs, d4T and AZT, interfere with the metabolism of fat, and fat metabolism is also involved in generating steroid hormones like testosterone and oestradiol, could one or both classes of antiretrovirals be causing hormonal havoc in some men?
The Chelsea and Westminster has contributed to a large European study of 900 HIV-positive people that will be published soon.
“It found that length of time on antiretrovirals was associated with sexual dysfunction, but no matter how you teased it out, you could not find an association with one drug or class,” reveals Dr Catalan.
“The main factors that were predictors of sexual dysfunction were:
  • Age – a stronger age effect than might have been anticipated

  • Self-reported depression

  • Taking antidepressants

…and really nothing else specific. Sexual dysfunction always has a complex aetiology.”
The study included women, too.
“We found rates of sexual dysfunction or dissatisfaction in women that were at least as high as in men. Unfortunately, women get left out all the time. Men’s sexuality is like an on/off switch, where pills may well be effective, but women’s sexuality seems more complex. Additionally, women may be too shy or traumatised to come forward – I see very few – and, of course, we don’t have a Viagra for women.”


Normal service will be resumed as soon as possible
Whatever the cause of sexual dysfunction, the effect is of a considerable degree of emotional distress and relationship difficulty for a group of people who already have more than enough reasons to find sex problematic.
The good news is that there is much that can be done about ED in particular, thanks to the advent of the phosphodiesterase inhibitors, like Viagra (sildenafil) and Cialis (tadalafil).
“I advise my patients to try out Viagra for first time by themselves,” says Dr Catalan. “By masturbating alone they can establish that it does work. If they’ve been very anxious about performance it can be disappointing if Viagra fails to conquer that anxiety.”


Can HAART and Viagra be safely combined?
PIs and NNRTIs are metabolised by the P450 3A4 enzyme in the liver, which also processes Viagra and Cialis. Consequently, combining these with anti-HIV drugs may produce high levels in the blood and worsen side-effects. Symptoms include flushing, headache, racing pulse, sweating, faintness, blurred vision and unwanted, painful erections. These symptoms are acutely magnified if you take poppers – plus a severe drop in blood pressure can also happen which can cause fainting or even death.
Pfizer, the manufacturers of Viagra, recommends taking Viagra at a reduced dose of 25mg when on PIs or NNRTIs. The European Agency for the Evaluation of Medicinal Products recommends that ritonavir should not be taken with Viagra. However, if the two drugs are co-administered, the dose of Viagra should not exceed 25mg every 48 hours. Since Viagra is actually available in three strengths – 25mg, 50mg and 100mg - Dr Catalan suggests starting at 12.5mg (i.e. half of the lowest-strength pill) and if that doesn’t work, increasing the dose to a maximum of 25mg.
Eli Lilly, the manufacturers of Cialis (available in 5mg, 10mg, and 20mg pills) recommends taking no more than 10mg when co-administered with PIs or NNRTIs, and no more frequently that once every 72 hours.
Levitra (vardenafil), from GlaxoSmithKline (GSK), appears to interact much more severely with HAART, and is not recommended at any dose with PIs or NNRTIs. A GSK study found that 800mg indinavir three times a day taken with 10mg vardenafil increased vardenafil peak levels sevenfold, and resulted in a 16-fold increase in total vardenafil exposure. Although specific interaction studies have not been conducted with ritonavir, other PIs or NNRTIs, GSK says they expect to see levels similar to those seen with indinavir, and Levitra “should be avoided” if you are taking PI- or NNRTI-based HAART.


Other options
Given these interaction issues, Dr Catalan also sometimes prescribes apomorphine, a drug that works in a completely different way, on the brain, rather than the penile blood vessels.
“It stimulates desire as well as improving erections,” he says. “Some patients really respond to it, others find it doesn’t work at all.”
More local non-systemic remedies are available, though less easy to use. These include Caverject, which uses a tiny needle to inject the vasodilator alprostadil, and Muse, which is a small alprostadil pill inserted into the urethra with an applicator. Caverject needles should never be shared, however, since there has been a case of HIV infection reported through this route.
Herbal remedies with Viagra-like effects also exist. The most effective is yohimbe, from the bark of an African tree. This works both by interfering with the same chemical pathway as Viagra and by stimulating the neurotransmitter dopamine, in a similar way to apomorphine.
However, yohimbe can cause similar, but worse, side-effects to Viagra. Serious adverse effects, including kidney failure, seizures and death, have been reported to the US Food and Drug Administration with products containing yohimbe and the herb is currently under investigation. Yohimbe’s levels in the body are also boosted by ritonavir and other P450 3A4 inhibitors, including grapefruit juice.
Ginkgo biloba is a herb that relaxes the walls of blood vessels and improves blood flow generally. One study has shown benefit in treating erectile and sexual arousal disorder in both men and women.5 Care needs to be taken if combining Ginkgo with anticoagulant medicines like warfarin, aspirin or vitamin E and also the diabetic drug, metformin.
When low testosterone is implicated in sexual dysfunction, testosterone injections or patches such as Testoderm, sometimes combined with other steroids, can often work wonders for loss of libido. “I find the injectable testosterone works best – testosterone propionate or Sustanon,” says Dr Catalan. “An injection will give you a sustained dose for two to three weeks. There are also subcutaneous implants that work for 2-3 months.
“Testosterone patches and gels also work, but the patches can cause irritation and patients tell me the gel is horribly sticky.”


The politics of Viagra
Pepe Catalan is very aware of the debate around Viagra and HIV - that prescribing erection-enhancers to HIV-positive men may enable them to have unsafe sex and transmit HIV. However, there appears to be no evidence in support of that argument. “A survey of gay men using gyms in London6 found those who were prescribed Viagra did not have very high rates of unprotected anal sex,” says Dr Catalan. “It was the men who ordered it off the internet who were more likely to use it to overcome the effects of recreational drugs, or just to have an instant hard-on – they were the ones who tended to use it irresponsibly.
“I have also prescribed Viagra on occasion to patients who lose their erection when they try to put on a condom. Even though this usually has a psychological cause, it enables some patients, as one said to me, to ‘have something to put a condom on’.
“In addition, the NHS only allows doctors to prescribe Viagra for certain conditions like diabetes and prostate surgery, and HIV is not one of those. Many HIV clinics pay for Viagra out of their general HIV funding, but that means patients cannot be sent to their GPs for repeat prescriptions.”


Go and talk to someone
Disclosure difficulty; fear of infecting others or of acquiring sexually transmitted infections (STIs); lipodystrophy, and other causes of poor body image; drug abuse and alcoholism; broken relationships – all these can lead to disaster when it comes to sex.
However, various kinds of sex therapy and counselling are available, from cognitive-behavioural solutions for premature ejaculation, to guided sex techniques for nervous lovers, to long-term therapy for the bereaved and the rejected.
Sexual happiness is as much a right of HIV-positive people as it is for anyone, so if you are having sexual problems you should not hesitate to ask for help.



References
1.Lamba H, et al. International Journal of STDs and AIDS, 15 (4): 234-4, 2004.
2.Lallemand F, et al. JAIDS 30: 187-190, 2002.
3.Colson AE, et al. JAIDS 30: 27-32, 2002.
4.Sollima S, et al. AIDS 15 (17), 2331-2333, 2001.
5.Cohen AJ, et al. Journal of Sex and Marital Therapy 24 (2), 139-143, 1998.
6.Elford J, et al. AIDS 15, 1409-1415, 2001.