People living with HIV (PLWH) and people who use drugs are vulnerable populations who may face barriers to accessing health services and may have irregularities in immune function. People with undiagnosed HIV infection may be particularly likely to have compromised immune function. However, research about whether/how HIV status is related to COVID-19-related health outcomes has been equivocal, and research on the predictors of COVID-19-related health service access/uptake has been limited in Sub-Saharan African settings. Among 470 participants of a peer-recruitment-based HIV-testing intervention in KwaZulu-Natal, we examined whether HIV status and/or hard drug use were associated with uptake of COVID-19 testing and vaccination, and whether they moderated the relationship between COVID-19 vaccination status and COVID-19 IgG antibody status. Women were significantly more likely than men to report testing for COVID-19 (OR = 1.84; p = 0.002) and being vaccinated (OR = 1.79; p = 0.002). Neither HIV status nor drug use was associated with likelihood of getting tested or vaccinated. Vaccinated participants (90% of whom obtained vaccines more than 6 months before the study) were significantly more likely to test positive for COVID-19 IgG antibodies (OR = 6.86; p < 0.0005). This relationship held true for subgroups of PLWH and participants with previously undiagnosed/uncontrolled HIV infection, and was not moderated by HIV status or hard drug use. These findings may suggest that both people who use drugs and PLWH were served as well as other people by KwaZulu-Natal’s COVID-19 response. However, gender-based disparities in COVID-19 service uptake suggest that special care should be taken during future COVID-19 outbreaks or other new epidemics to improve access to related healthcare services among men in this region.