Unique Populations Treatment of pregnant women, and persons with co-infections including tuberculosis, hepatitis, or renal insufficiency can alter treatment recommendations. While a PK study evaluating DTG in pregnant women is underway, to
date no clinical trials have evaluated DTG use in pregnant women, though animal studies demonstrate that DTG can cross the placenta . The FDA label states that DTG should be prescribed in pregnancy only if potential benefit justifies Selleck Emricasan the potential risk, category B . DTG should be given twice daily when co-administered with rifampin (600 mg daily) as rifampin decreases DTG exposure by approximately 50% due to minor metabolism via CYP3A4 . Rifabutin also reduces DTG trough concentration by about 30%, but this reduction
maintains concentrations above the PA-IC50 (0.016 μg/mL) and does not require dose adjustment [24, 43, 44]. Transaminase monitoring for hepatotoxicity is recommended when treating patients with hepatitis B and/or selleck chemical hepatitis C co-infection. Those with mild-to-moderate hepatic impairment (Child–Pugh Score A or B) do not require dose adjustments, but treatment in severe hepatic impairment (Child–Pugh Score C) is not recommended. DTG has not been studied in patients on dialysis, and those with severe renal impairment may have decreased drug concentrations that could dampen therapeutic effect and lead to resistance [24, 44, 45]. The Future Dolutegravir is now a recommended first-line agent in the United States for both treatment-naïve or treatment-experienced INSTI-naïve (once-daily dosing) and treatment-experienced with suspected INI-resistance (twice-daily dosing) adults and adolescents
at least 12 years old weighing a minimum of 40 kg . In resource-limited settings, ART is typically limited to combination NRTI/NNRTI as first-line regimens, and NRTI/boosted PI regimens as second line. Third-line regimens containing integrase inhibitors are rare, and it is unclear if they will become available in a resource-limited context. A fixed-dose combination of ABC/3TC/DTG has shown bioequivalence to individual formulations  and could hold promise, especially for resource-limited settings such as sub-Saharan Africa where Arachidonate 15-lipoxygenase the HIV burden is high, the HLA-B*5701 mutation is rare, and renal monitoring for regimens that include tenofovir are limited. In 2010, ViiV Healthcare announced the intention to make their patents, including DTG, available to generic manufacturers under a royalty-free agreement. Whether these negotiations will result in the ability of resource-limited settings to access DTG is uncertain [47, 48]. To date, clinical trials of DTG have primarily included white males from developed countries. Future studies that include more women and children, non-subtype B virus, HIV-2 (primarily West Africa), and non-white ethnicity are Selleck Selumetinib encouraged.