The truth about Truvada

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Post by Neil McKellar-Stewart01 Dec 2013

Truvada is a combination of two antiretroviral (ARV) drugs: tenofovir (TDF) and emtricitabine (FTC) and is one of the mainstay backbones for treating people living with HIV. It is highly effective when used with other ARVs and has very few short-term side-effects.

Truvada has also been investigated in several major clinical trials as the combination of choice for use in people at high risk of acquiring HIV. These include the HIV-negative partners of PLHIV, people who inject drugs (specifically those who may share injecting equipment), and gay and bisexual men who have unprotected anal intercourse with multiple partners.

The use of pre-exposure prophylaxis (PrEP) is not new. Childhood vaccinations and antibiotics to prevent malaria while travelling or a staph infection while in hospital are all now common practice.

Truvada is regarded as an effective drug for PrEP because tenofovir has a long half-life and concentrates particularly in the mucous tissues within the rectum; while FTC concentrates in the genital tissues. So, together they act to reduce the risk of HIV transmission through sexual activity.

Three PrEP demonstration studies (in Victoria, Queensland and NSW) are underway to see how oral PrEP might be implemented in Australia.

Safety is an obvious issue for those considering enrolling.

As noted above, Truvada has a very good safety profile. Soon after commencing some people experience mild side-effects including diarrhoea, nausea, headache or fatigue. All of which generally resolve within a month.

Of more concern are metabolic changes resulting from long-term use. Tenofovir is excreted through two separate parts of the kidney and has been shown to cause slight changes in the structure and function of what are termed the proximal tubules. This may result in lower than optimal levels of phosphate and other molecules needed for healthy bone development and maintenance. Such events are uncommon and in their severest form exceedingly rare.

The vast majority of PLHIV taking tenofovir (which is also in the single tablet regimens Atripla and Eviplera) suffer no significant decline in kidney function and continue to maintain good bone health.

Lifestyle factors such as smoking, low calcium and vitamin D, along with increasing age and HIV infection itself, probably contribute as much as anything else to any losses in kidney or bone health.

The results of the only large scale controlled trial investigating the safety of Truvada as PrEP have recently been published6.

The study found that over two years, there were no significant differences in measures of kidney function between those who took PrEP and those who did not. Adherence was high and the only sero-conversions in the study were those in the non-treating arm. All this was as expected and good news.

As part of the screening process, a subset of men had their bone mineral density (BMD) measured at their hip, lumbar spine and femur 7. A few were found to have reduced BMD already and were excluded from the trial. Interestingly, amphetamine or inhalant use was associated with a five-fold increased risk of decreased BMD. Conversely, use of calcium, multivitamin and vitamin D supplements appears to reduce the risk by 70%. Among those remaining men who received Truvada over two years, there were small but significant decreases in BMD compared with those who received the placebo. These losses occurred mainly in the first 12 months and are consistent with other studies.

The conclusions which can be drawn from this study and knowledge we have of how TDF is processed through the kidneys are:

  • Adverse effects on kidney function are rare and probably of very limited significance for people taking TDF over 24 months.
  • However, it is known that reductions in function of the tubules in the kidney are associated with use of TDF. Non-steroidal anti-inflammatory drugs (NSAIDs) and treatments for herpes (aciclovir) may increase concentrations of TDF in the tubules and pose an increased risk of kidney damage.
  • For this reason, it is important to confirm good kidney function prior to using TDF or TDF/FTC. This is measured by standard blood and urine analysis.
  • Pre-existing risk factors for poorer kidney health need to be investigated by your doctor. These include age over 50 years, smoking, raised blood pressure (hypertension), overweight and diabetes.
  • Significant decreases in BMD may occur in the first 12 months of TDF use.
  • People considering using TDF for PrEP should ensure the best possible bone health and should be screened for vitamin D status. Use of calcium and multivitamin supplements may ensure that bone health is good before commencing TDF and during its use. People with a history of bone disease or low-impact bone fractures should obtain medical advice before using TFD/FTC.
  • HIV ARVs including TDF/FTC are generally safe for most people; however, all of them have some side-effects, and for this reason should not be used without prior screening and ongoing medical care.
  • Use of TDF/FTC should be consistent to ensure that HIV infection does not occur. We know that the drug works if it is in sufficient concentration in the blood stream. If sero-conversion occurs and it is not identified, it is possible that with inconsistent use of PrEP, HIV may develop resistance to TDF/FTC. This may seriously complicate future HIV treatment.

The USA is the first country to license Truvada as PrEP for people at high risk of acquiring HIV (including those listed above). It’s important to note that no drug is currently licensed in Australia for PrEP use. Doctors are unable to prescribe HIV drugs for this purpose. Some gay men and others at high risk of acquiring HIV may choose to obtain generic versions from reputable overseas suppliers of online HIV medicines. People in this situation can be assured that the risk of adverse events is low, however, they should ensure that they discuss their use with their doctor/s and that they receive ongoing monitoring of their general health (including HIV/STI screening and kidney function).

Because TDF/FTC is licensed for PrEP in the USA there are a range of authoritative, reliable websites proving information it its use, these include: