Background: In Malaysia, there are still lack of studies related to the challenges of people infected with HIV (PIWH). Therefore, this study was conducted to explore the experiences of PIWH and how they cope with HIV. Methods: This qualitative study was based on a social constructivist and grounded theory approach. A total of 12 PIWH were selected by purposive sampling, all of whom participated in semi-structured and audio-recorded interviews, which were supported with non-participant observations and diary entries on three occasions for each participant. The interviews and diaries were transcribed and analysed using the grounded theory approach, which was assisted by utilizing NVIVO-8 to identify the themes related to the experiences of the participants. Results: PIWH experienced challenges related to their career and relationships with family and others. These challenges led to difficulties in gaining employment and career development, as well as feelings of denial, being uncomfortable, rejection, and labelling. They found that their lives were totally and dramatically changed after being tested positive for HIV. Conclusions: Among PIWH, HIV impacted relationships with significant others and career development. The absence of support and acceptance from significant others affected the ability of PIWH to cope with their daily challenges. The results of this study have implications for policymakers in terms of gaining sufficient knowledge and awareness to provide prevention programmes for HIV/AIDS.