Does the time difference between Karachi and São Paulo change during the year?

No. The gap stays at 8h all year.

When is the best time to call São Paulo from Karachi?

There is no overlap between standard working days, so one side has to call early or late.

Karachi is 8h ahead of São Paulo. This gap is the same all year — neither city shifts its clocks relative to the other.

Karachi

Pakistan

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São Paulo

Brazil

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A 9-to-5 working day in Karachi does not overlap one in São Paulo at all — somebody has to take the call outside office hours.

City	Time zone	UTC offset
Karachi · Pakistan	Asia/Karachi	UTC+5
São Paulo · Brazil	America/Sao_Paulo	UTC−3

What is the time difference between Karachi and São Paulo?: Karachi is 8h ahead of São Paulo. This gap is the same all year — neither city shifts its clocks relative to the other.
Does the time difference between Karachi and São Paulo change during the year?: No. The gap stays at 8h all year.
When is the best time to call São Paulo from Karachi?: There is no overlap between standard working days, so one side has to call early or late.