Double-stranded viral DNA enters the host cell nucleus through pores in the nuclear membrane. Another viral enzyme, integrase, then inserts the double-stranded viral DNA at random into the DNA of the host. The viral DNA then becomes integrated into the human DNA, turning the host cell into a "factory" for manufacturing more virus.

In the normal human cell, DNA in the nucleus tells the cell which proteins to produce. As the first step in this process, DNA acts as a template to produce messenger RNA (mRNA), which communicates the DNA's instructions to other parts of the cell. A cell infected with HIV contains viral DNA as well as human DNA, and both are copied into mRNA. The mRNA leaves the nucleus and enters the cytoplasm, where it delivers its instructions for making proteins.