Human Immunodeficiency Virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its lifecycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we employ a combination of ribosome profiling, disome sequencing and RNA sequencing. We found that the initial host response to viral infection is translationally regulated, and subsequently gives way to transcriptomic changes as the infection progresses. We show that HIV-1 mRNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in translational efficiency of host genes that are implicated in host cell translation. We observed ribosomal collisions in Gag-Pol upstream of the ribosome frameshift site that we attributed to a novel RNA structural fold using RNA structural probing and single molecule optical tweezers. Antisense oligos designed to break this structure decreases frameshifting efficiency. Overall, our work highlights the complexity of HIV-1 gene regulation and will provide a key resource for decoding of host-pathogen interactions upon HIV-1 infection.