The South African National AIDS Council (SANAC) which brings together government, civil society and the private sector as a collective has been relentless in its quest to turn the tide against the HIV, STI and TB epidemics and ensure that no one is left behind. The country is embarking on the development of a 5th generation National Strategic Plan for HIV, TB and STIs: 2023 – 2028, but the COVID-19 pandemic, including lockdowns, has had far-reaching effects on especially key and vulnerable populations. Whilst these measures as well as community instabilities (looting) and natural disasters (floods) impacted on the implementation of programmes and services, South Africa introduced innovative ways to ensure resilient systems and responses at community level aligned with the 4th industrial revolution. This resulted in highly effective and high-impact interventions backed by evidence-informed analysis, which shows that there is progress as seen in data comparison between 2020 and 2021.