Final answer:
The first generation single-drug therapy for HIV failed in the long run due to Development of drug resistance option (c). The development of combination therapy, known as HAART, was a breakthrough in HIV treatment as it decreased the chances of the virus developing resistance to multiple drugs simultaneously.
Step-by-step explanation:
The first generation single-drug therapy for HIV, specifically AZT (azidothymidine), failed in the long run due to the development of drug resistance option (c). When AZT is used individually, the high mutation rate of the virus allows it to easily and rapidly develop resistance, limiting the drug's effectiveness. This is why a breakthrough occurred with the development of HAART (highly active anti-retroviral therapy) that involves a combination of different drugs, making it more difficult for the virus to develop resistance to multiple drugs at the same time.