Truvada and Isentress: Effectiveness as HIV PEP Treatment
One of the standard regimens for treatment-naïve patients, based on the recommendations of the Department of Health and Human Services (DHSS), is a combination of Truvada + INSTI (integrase strand transfer inhibitor). Official HIV treatment guidelines are usually updated from year to year to reflect new findings from research trials and real-world effectiveness.
Until recently, Truvada, a two-drug combination of emtricitabine (Emtriva) and tenofovir DF (Viread) plus a third drug dolutegravir (Tivicay), is the mainstay treatment for pre- and post-exposure prophylaxis. However, in May 2018, the European Union’s drug regulatory agency and the European’s Medicines Agency (EMA) cautioned about the use of Tivicay in pregnant women with HIV. 3 The drug was linked to birth defects in a large observational study in Botswana. The Centers for Disease Control now recommends raltegravir (Isentress) in lieu of dolutegravir for post-exposure prophylaxis (PEP). The CDC issued statements in the avoidance of Tivicay for patients:
- Who are sexually active and of childbearing potential or women who have been sexually assaulted and are not currently using an effective birth control method;
- Who are in early pregnancy since the risk of developing neural tube defects in unborn infants is during the first 28 days.
Truvada and Isentress combo for PEP
PEP has been found to significantly reduce the risk of HIV infection in cases of possible exposure to the virus. But in order for the preventive tool to work, it must be started within 72 hours of exposure, and the antiretroviral regimen must be taken for 28 consecutive days. Late initiation and missing a dose will render the drug ineffective. In facts, animal studies suggest that PEP failure rates increase within 48–72 hours of exposure. The CDC recommends Isentress as a preferred regimen for pregnant women and those of childbearing potential. Prior to initiation of PEP, all women who may possibly get pregnant must have a pregnancy test performed. If a non-pregnant woman is required to take Tivicay, she must use an effective birth control method throughout treatment. If pregnancy is confirmed in the first trimester, the patient should use the combination of Truvada and Isentress or other suitable alternative.
Tivicay vs Isentress
In the UK, a protease inhibitor (PI) combination Kaletra (lopinavir/ritonavir) used to be the drug of choice for PEP until 2014. Isentress replaced Kaltera in the same year because the combination of Truvada and Isentress is associated with fewer side effects compared to the previous recommendations. Raltegravir is also more rapidly absorbed than the PI combo.
Isentress is the first HIV-1 integrase inhibitor. It works by blocking the strand transfer activity of the HIV enzyme integrase, therefore preventing the integration process. While HIV can infect a cell, it cannot make copies of itself because of the inhibitory effect of the drug. Just like Tivicay, a similar INSTI drug, it can be taken without regard to food. In several studies, Isentress and Tivicay have both demonstrated efficacy as PEP, but the former was linked to slightly higher side effect risk and discontinuation rates. A two-year study comparing dolutegravir and raltegravir for the treatment of HIV-positive volunteers showed the following results:
- Virological failure was reported at 5% for dolutegravir-containing regimens and 10% for raltegravir-based regimens.
- One volunteer from raltegravir group developed viral mutation and resistance to INSTIs
- Response to therapy:
Dolutegravir regimen – from participants with CD4 count of less than 350 cells, 78% achieved a viral load of 50 copies/ml. From participants with CD4 count of less than 200 cells, 71% achieved a viral load of 50 copies/ml.
Raltegravir regimen – 69% of those with baseline count of 350 cells achieved a viral load of 50 copies/ml while only 56% of those with baseline count of 200 cells achieved a viral load of 50 copies/ml.
- Both regimens showed similar rates of reported side effects, but two participants had discontinue treatment due to side effects.
- There were no significant lab test results for both regimens. There were small increases in creatinine levels for dolutegravir but researchers concluded that such results pose no harm.
- The study did not find any difference in participants’ heart health. Changes in heartbeat or presence of abnormal heart rhythms were insignificant. One participant in the dolutegravir group experienced slightly abnormal heart rhythm.
To summarize, Isentress is a good alternative to Tivicay for PEP treatment in pregnant women and those who are planning to get pregnant. Results were similar regardless of baseline viral load and additional drugs or nukes in the regimen. Both drugs caused a relatively low rate of mild to moderate side effects in the first year of treatment.