Initial data gathered from seven separate studies found tenofovir alafenamide (TAF) is just as effective as tenofovir disoproxil fumarate (Viread, TDF), with fewer side effects to the kidneys and bones, when used in cisgender women. These results, presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle, are similar to those found in cisgender men.
TDF was approved for use in patients with HIV in 2001 and for use in those with hepatitis B in 2008. The drug was highly successful and became a staple of most HIV treatment regimens, but was known to cause kidney toxicity and loss of bone density in some patients. In 2015, the Food and Drug Administration (FDA) approved the tenofovir prodrug TAF, which can be effective in smaller quantities relative to the original.
TAF is now included in a number of commonly used antiretroviral combination pills, most notably bictegravir/emtricitabine/TAF (Biktarvy) and emtricitabine/TAF (Descovy), which are among the list of first-line drugs currently recommended in U.S. first-line HIV treatment guidelines. For the most part, research has shown that TAF is equally effective as TDF with fewer negative side effects. But, as researcher Melanie Thompson, M.D., with AIDS Research Consortium of Atlanta pointed out in her presentation, the majority of participants in these studies were men.
Though women make up 52% of adults living with HIV worldwide, they are often underrepresented in clinical trials, and health care providers are forced to assume that women will have the same results as men. For this analysis, an all-women team of researchers looked at seven studies that included a total of 779 cisgender women. Two of the studies (representing 260 of the women) were of individuals who were treatment-naive. The other five studies (representing 519 women) were conducted among virally suppressed individuals who were switching from a TDF regimen to TAF.
The data show that the two tenofovir treatments have similar efficacy rates. At 96 weeks, the FDA snapshot showed 86% viral suppression for women on TAF and 85% for those on TDF. This is close to what research has found in men -- 87% viral suppression on TAF and 85% on TDF.
The reporting of adverse effects was also similar among women taking TDF and TAF. The most common side effects for treatment-naive women on both drugs included nausea, swelling of the throat and nasal passages, headache, upper respiratory infection, diarrhea, joint swelling and pain, dizziness, and back pain. Again, this was similar to the common side effects found in men on both medications.
The differences between the two drugs were most evident when it came to kidney toxicity. The analysis looked at two biomarkers that could indicate kidney injury and found that both were lower in women taking TAF than in those on TDF. Moreover, no women on TAF developed proximal renal tubular dysfunction, which is known to happen on TDF. The researchers referred to the lower adverse renal effects as a "highly treatment significant difference" between the two drugs.
The researchers also looked at adverse effects related to bone density. Women who started treatment with TAF had less bone mineral density decline than those who started on TDF. And, women who switched from TDF to TAF had improvements in bone mineral density. These were similar to the results found in men.
The analysis of the pooled data suggests that women have similar experiences with tenofovir to those of men. The researchers conclude that starting therapy with TAF or switching to TAF has significant safety advantages for women, while offering the same amount of viral suppression as treatment with TDF. Melanie Thompson ended her presentation by saying that "the other finding from this analysis is that it is both feasible and awesome to work with an all-female research team."