This week, leading experts offer a possible road map for accelerating the way we conduct HIV cure research. We also read updated results on a two-drug regimen as HIV maintenance therapy. And we get data on bone mineral density changes for three different regimens.
To beat HIV, you have to follow the science!
"How can we make significant gains in HIV cure research in the next five years?" ask leading cure researcher Jintanat Ananworanich M.D., Ph.D., and Nobel laureate Francoise Barré-Sinoussi, Ph.D., in an essay published in The Lancet HIV. To date, there remains only one case of a sustained HIV cure, in contrast to 35-million people worldwide living with HIV.
Based on current studies, using a single therapy to eradicate the virus seems very unlikely. Instead, a combination of therapies is a better strategy (much the way combination antiretroviral therapy changed the way we treat HIV). However, as the authors note, researchers struggle to identify what these combinations would be.
The current approach to clinical trials requires that each single therapy be studied in animal models first, then in humans. Then, if that single therapy is combined with another combination, the entire process starts over again. Each step takes years and puts an HIV cure too far in the future, according to the authors. Instead, Ananworanich and Barré-Sinoussi provide a possible road map for accelerating combination cure research for HIV.
In this essay, Alexandra Calmy, M.D., Ph.D., and Delphine Sculier, M.D., M.P.H., argue that it's time to consider single-drug regimens as maintenance therapy for patients living with HIV. Maintenance therapy is currently being studied for patients who have already achieved undetectable viral loads. Reducing the number of drugs would potentially reduce pill burden, spare certain drugs and offer cost savings. Interest in maintenance therapy has renewed in recent years, given improvements in HIV drugs, and particularly the integrase inhibitor class.
The integrase inhibitor dolutegravir (Tivicay, DTG) is very potent at low doses, with a strong resistance profile, and could be coformulated with lamivudine (3TC, Epivir). We'll need large randomized control studies to determine if dolutegravir could work alone as maintenance therapy or would need to be combined with lamivudine, the authors write.
The LATTE study has already demonstrated that the investigational integrase inhibitor cabotegravir plus long-acting rilpivirine (Edurant) works as maintenance therapy. Additionally, the recently approved coformulation of darunavir/cobicistat (Prezcobix) offers a potential option for maintenance, the authors suggest.
Updated results of the LATTE study show that cabotegravir plus rilpivirine continues to work as maintenance therapy at 96 weeks, according to study results published in The Lancet. The study followed 243 patients, 181 of whom were put on maintenance regimen containing one of three doses of cabotegravir and 62 of whom remained on a regimen containing efavirenz.
When last reported, the 48-week results found that 82% of those taking cabotegravir (all doses) plus rilpivirine maintained viral suppression versus 71% in the efavirenz group. Now, the 96-week results show that 76% of those taking cabotegravir plus rilpivirine maintained viral suppression versus 63% in the efavirenz group.
The study authors suggest moving forward with cabotegravir at 30 mg for further study. The LATTE study will also assess whether long-acting injectable formulations of cabotegravir and rilpivirine could work as maintenance therapy, with the hope that monthly or quarterly injections could maintain viral suppression in patients living with HIV.
In the Clinic
To assess bone mineral density (BMD) changes from three different HIV regimens, researchers followed 328 treatment-naive patients who were randomized to receive tenofovir/emtricitabine (Truvada) with either atazanavir (Reyataz) boosted with ritonavir (Norvir), darunavir (Prezista) boosted with ritonavir, or raltegravir (Isentress).
After 96 weeks, average BMD loss in the spine was -4.0% in the atazanavir group, -3.6% in the darunavir group and -1.8% in the raltegravir group. Average BMD loss in the hip was -3.9% in the atazanavir group, -3.4% in the darunavir group and -2.4% in the raltegravir group.
These findings showed that average BMD losses were similar for those receiving the two protease inhibitors (atazanavir or darunavir), but lowest for those receiving the integrase inhibitor raltegravir, according to the researchers. Further analysis showed that higher baseline markers of inflammation and immune activation were independently associated with subsequent BMD loss.
Silicone vaginal rings offer an easy and effective way of preventing sexually transmitted infections (STIs), including HIV, for women. Researchers in France have developed a silicone ring that delivers a slow, continuous stream of antiviral drugs, according to a study presented at ICAAC/ICC 2015 in San Diego.
Based on the study's preliminary results, the rings can release 3 to 5 mg per day of tenofovir (Viread) for a period of time of at least 50 days. The rings can also release 1.5 to 3.5 mg per day of acyclovir, a common herpes simplex (HSV) medication. Both doses can neutralize HIV and HSV present in semen, the study reports.
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