OBJECTIVES: Increasingly, human immunodeficiency virus (HIV) infection is managed as a chronic condition. Payers in the United States (US) typically manage chronic conditions as cost-effectively as possible. One element of cost containment is to institute policies driving utilization of less-expensive generic medications. As generic HIV drugs become available, concerns arise that “de-simplifying” HIV treatment by incentivizing use of generic components of fixed-dose combination (FDC) treatments will impact adherence, resulting in adverse treatment effects. This study evaluated US payers’ likelihood to incentivize patients/physicians from branded FDCs toward a combination of generic single-dose drugs.  METHODS: We conducted targeted research of published literature and payer Web sites to identify information relevant to HIV coverage polices. This informed a discussion guide for one-on-one interviews with 10 payers from US commercial health insurance companies. Participants were recruited to ensure diversity from organizational sizes and geographical regions; interviews were double-blinded (i.e., payer and pharma). RESULTS: Payers indicated HIV management is increasingly perceived as chronic (e.g., diabetes, hypercholesterolemia, schizophrenia) rather than life-threatening and that treatments, while costly, lead to significant savings in medical benefits and ultimately leave medication decisions to specialists.  Payers are cautiously examining potential savings and were willing to institute modest management  for generics (tier 1) while keeping branded FDCs on preferred tier 2 (branded preferred copay). Payers were unwilling to institute, high cost-sharing co-insurance, prior authorizations, or require failure for members to access branded HIV medications presently or in the near future.  CONCLUSIONS: Payers recognize the complexity of treating HIV, the role of adherence, the high cost of failure and the public health component of preventing resistance.  We found payers to cautiously look at potential cost savings in medication management until all FDC components become generic.  We found no widespread desire to drive generic adoption in HIV treatment, and little interest in the “de-simplification” of currently available FDCs.