HIV proviral DNA integration into the host chromosome is carried out by integrase becoming an important target antiretroviral therapy. Raltegravir was the first integrase inhibitor approved for use in HIV therapy and elvitegravir is in the late phase of clinical development; both show good results in monotherapy studies and may be used worldwide for rescue therapy. In this work we analyzed 57 integrase sequences obtained from samples from drug-naive and first line regime-failing patients from Maputo, Mozambique, to evaluate the presence of natural polymorphisms and resistance mutations associated with raltegravir and elvitegravir. No major mutations conferring resistance to integrase inhibitors were found and polymorphic accessory mutations were solely observed in low frequency among subtype C sequences-L74M (3.4%), T97A (1.8%), and E157Q (1.8%)-suggesting that this new antiretroviral drug class will be effective in Mozambique providing a good perspective to the introduction of this class of drugs in that country.