What this study adds: This study addresses the critical data gap regarding vaccine uptake among South African PLWH. It reveals low uptake (24.3%) and limited vaccine literacy. Crucially, it identifies healthcare provider recommendations as the primary catalyst for acceptance, providing a clear evidence-based strategy to improve clinical outcomes and guideline implementation.

Vaccine-preventable diseases (VPDs) continue to impose a significant clinical and economic burden in South Africa (SA) and globally. In the United States (US), an estimated 40 000 to 50 000 adults die from VPDs annually,¹ with the burden disproportionately affecting at-risk populations, such as individuals at risk of severe clinical outcomes because of underlying comorbidities as well as those with a greater risk of exposure to VPDs.² Countries in sub-Saharan Africa account for 34% of the global VPD burden,³ while at the same time bearing one of the world’s highest HIV burdens – an estimated 7.8 million people were living with HIV (PLWH) in South Africa in 2023.⁴

Hepatitis B virus (HBV) is one of the most common VPDs among PLWH because of overlapping transmission routes.^5,6 In SA, HBV prevalence in this group ranges from 0.4% to 23%.⁷ Furthermore, despite antiretroviral therapy (ART), PLWH remain at heightened risk of invasive pneumococcal disease (IPD). Meiring et al.⁸ reported a 43-fold higher incidence of IPD in PLWH receiving ART compared to their HIV-negative peers. People living with HIV have an increased risk of mortality from human papilloma virus (HPV)-associated malignancies than the general population. This increased risk is particularly significant in women.⁹ Interestingly, the association between HIV and susceptibility to meningococcal infections has been debated across different countries. Earlier African studies did not find a clear link between HIV and meningococcal infections.^10,11 However, Cohen et al.¹² reported an 11-fold higher risk among PLWH in SA, and further studies are necessary to quantify the morbidity and mortality associated with meningococcal disease among PLWH. In Africa, there are limited data on the burden of varicella zoster virus (VZV) among PLWH.⁷ Diphtheria, pertussis, and tetanus follow similar trends,¹³ although global surveillance gaps limit understanding of their true burden in PLWH.

In 2018, the South African HIV Clinicians Society (SAHCS) published guidelines for the vaccination of HIV-positive adolescents and adults in South Africa.⁷ So far, these remain the only guidelines published in the African region and include similar recommendations to those of some international guidelines.^14,15 The SAHCS guidelines advise individuals to receive vaccinations for influenza, pneumococcal disease, meningococcal disease, HPV, tetanus, diphtheria, and pertussis. Additionally, vaccinations for hepatitis A and B are recommended, as well as for measles, mumps and rubella (MMR) for individuals with CD4 cell counts above 200 cells/uL.⁷ The SAHCS guidelines do not recommend the live-attenuated herpes zoster vaccine (Zostavax) for PLWH because of limited epidemiological data supporting its use in Africa.⁷ In contrast, some international guidelines do recommend Zostavax for PLWH, but only those with CD4 cell counts above 200 cells/uL. This recommendation is based on promising clinical trial data and expert opinion, but with limited evidence on long-term effectiveness.^14,15 The recombinant herpes zoster vaccine (Shingrix) was not available in South Africa at the time the SAHCS guideline was published.

The reasons for low vaccination rates among PLWH reported in many countries are multifactorial. A study investigating self-reported vaccination coverage in Germany found that CD4 cell count had the strongest association with vaccine uptake, with CD4 cell count above 200 cells/uL being associated with higher vaccination coverage.¹⁶ These results were corroborated in a study conducted by Johnson et al.,¹⁷ which found that participants with CD4 cell counts less than 200 cells/uL were approximately 9-fold less likely to be up to date on all vaccinations compared to those with CD4 cell counts above 200 cells/uL. An African cohort study assessing HIV clinic visit adherence found that the reason ‘Feeling ill’ accounted for one of the top five reasons for missed clinic appointments, and CD4 count < 200 cells/uL was significantly associated with missing expected visits.¹⁸ This suggests that illness associated with advanced HIV disease may play a role in the ability to follow up with clinic appointments that is reflected in adherence assessments. The relationship between immunological status, clinic attendance and vaccine uptake remains insufficiently explored, however, and warrants further investigation in the South African context. Other barriers to uptake often include lack of information, forgetfulness, and poor provider communication. In a Belgian study, 89% of PLWH were unaware of vaccine recommendations, 38% lacked information on vaccination, and 6% did not see the need for vaccination.¹⁹ A Ugandan study assessing the uptake and acceptability of COVID-19 vaccines found that 90.5% of PLWH trusted vaccine information from healthcare providers more than any other source.²⁰

Concerns over vaccine safety and side effects also persist. In the United Kingdom (UK), 23% of PLWH refused the influenza vaccine because of a fear of adverse effects.²¹ However, a multicentre study involving 30 000 PLWH in the US found no long-term negative impact of influenza vaccination on CD4 cell counts, viral loads, or disease progression. It was further revealed that some patients not receiving ART experienced slight increases in HIV viral loads and reductions in CD4 cell counts following influenza vaccination, and most often normalised 2 to 6 weeks after vaccination.²²

The SAHCS guidelines note that vaccines are often not available at the points of care where PLWH receive treatment, while vaccine cost may serve as an additional barrier to access.⁷ This gap may reflect structural barriers within healthcare systems, as vaccination services are not consistently integrated into routine HIV care. Despite these insights, there remains a paucity of data regarding the accessibility of vaccines recommended by the SAHCS for PLWH. The aim of this study was to investigate vaccine uptake and the factors influencing knowledge and acceptance of vaccination among PLWH attending a tertiary centre infectious diseases clinic, to inform policy and guide interventions to improve vaccine uptake.

This study used a prospective cross-sectional audit and retrospective record review. Patient interviews provided self-reported data on demographics, vaccine uptake, knowledge, and acceptance, while review of the patient files was used to verify HIV monitoring results and medical history.

Data collection was carried out from 01 to 30 June 2023 at the Infectious Diseases Clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), a tertiary teaching hospital in Johannesburg, Gauteng, South Africa’s most urbanised province.²³ Gauteng has the fifth highest HIV prevalence nationally (17.6%), with the highest burden among adolescent girls and young women (35%).²⁴ The CMJAH Infectious Diseases Clinic serves approximately 14 400 to 19 200 patients annually.²⁵ Adults (≥ 18 years) living with HIV were approached during their waiting times for consultation or medication pickup. On average the Infectious Disease Clinic receives approximately 60–80 patients per day. A convenience sampling method was used, whereby patients present at the clinic during the study period were approached and were invited to participate. Prior to the interview, patients willing to participate were provided with an information sheet and consent form, which outlined the study’s purpose and time commitment. The interviews took place in a private consulting room, away from any queues, and lasted no longer than 10 min per participant.

A total of 107 PLWH were interviewed. Most respondents were women (67.3%), and the mean age was 47 years. The majority of participants had completed up to secondary level education (72.9%), and more than half (54.2%) were unemployed. Most participants (57.0%) reported living with HIV for between 11 and 20 years (Table 1).

Among the patients, the most common prior or current infection was tuberculosis (TB) (76.6%), followed by shingles (17.1%) and HBV (15.1%). Nearly all participants (99.1%) were on ART, but only 36.2% were aware of their specific ART regimen. Awareness of key clinical indicators was low, with only 29.0% aware of their HIV viral load and 11.2% aware of their CD4 cell count. Among participants with available data, 76.3% had an undetectable viral load (< 50 copies/mL). The clinical characteristics of the study participants are detailed in Table 2.

People living with HIV are at heightened risk for VPDs, which can lead to severe outcomes. Despite global recommendations for routine adult immunisation in this population, real-world data on vaccine uptake remain limited, particularly in sub-Saharan Africa. This study, the first to assess uptake of recommended vaccines among PLWH in South Africa, reveals a concerningly low uptake, with only 24.3% of the cohort having received at least one adult vaccine (excluding COVID-19 vaccines) post-HIV diagnosis. By comparison, a 2016 Brazilian study reported a 60.5% vaccine uptake rate among PLWH.²⁶ In our cohort, coverage was limited to only four vaccines – influenza, hepatitis B, herpes zoster (shingles), and pneumococcal vaccines, highlighting gaps in uptake of recommended vaccines according to broader HIV clinical guidelines. Influenza had the highest uptake (76.9% of vaccinated participants), likely driven by annual campaigns and availability. This finding aligns with international data presented in the study conducted in Brazil which showed that 71.8% of their cohort had received the annual influenza vaccine.²⁶ In contrast, pneumococcal vaccine uptake was just 3.8%; this is similar to the 4.4% reported in a study conducted in Denmark.²⁷

Our study cohort was predominantly women (67.3%), and female participants were five times more likely to have been vaccinated in univariable analysis, a finding that echoes prior research showing women engage more actively with healthcare.²⁸ However, this association lost statistical significance in the final adjusted model. Most participants were over 40 years of age, and age did not significantly affect vaccine uptake. Socioeconomic challenges were apparent, with the majority of the cohort having only secondary level education (72.9%) and more than half being unemployed (54.2%). However, neither educational attainment nor employment status was significantly associated with vaccine uptake (Table 1). This supports existing evidence that HIV disproportionately affects lower socioeconomic groups,²⁹ which may contribute to knowledge and barriers in accessing immunisation services.

Clinical factors proved critical predictors of vaccine uptake. Participants with a viral load < 500 copies/mL were over 10 times more likely to be vaccinated in univariable analysis. This suggests that better-controlled disease acts as an indicator for overall proactive health engagement. Prior studies reported a CD4 > 200 cells/uL was associated with increased vaccine acceptance.^16,17 Our study found no significant association between CD4 count and vaccine uptake. This lack of correlation may reflect hesitancy among both patients and providers around vaccinating immunocompromised individuals, potentially overriding CD4 cell count status as a predictor. South African HIV management guidelines do not recommend routine CD4 cell count measurement among PLWH on ART once the CD4 cell count is above 200 cells/uL. This may result in inconsistent CD4 cell count data that is not contemporaneous.

A history of opportunistic infections was common, with TB being the most prevalent. The most common VPD was herpes zoster (shingles), followed by hepatitis B. This may explain the greater awareness of vaccines for these specific diseases. Participants who received a vaccine post-HIV diagnosis also often had children and were aware of their own childhood vaccinations, suggesting that prior exposure to or engagement with immunisation, through parenting or personal experience, may build knowledge and acceptance. Furthermore, knowledge of details of one’s HIV care was significantly associated with uptake. Those unaware of their ART medication were 70% less likely to have received vaccination, and awareness of one’s viral load also significantly increased the likelihood of uptake. This finding aligns with studies linking health literacy with proactive health decisions and underscores how empowerment through education drives better clinical outcomes.³⁰ Interestingly, our analysis comparing self-reported clinical data with documented records found no statistically significant association between the accuracy of self-reporting viral load or CD4 count and adult vaccine uptake; however, this was a small subset of the total cohort. In terms of diagnosed conditions, influenza showed the highest agreement between self-report and clinical documentation.

Vaccine hesitancy persists in PLWH, often because of safety concerns, mistrust, and misinformation.^31,32,33 Although not statistically significant, this study suggested that participants who believed vaccines were safe or prevented disease were more likely to be vaccinated. Those who did not fear adverse effects on their HIV condition also had higher acceptance. Crucially, and of great importance, a healthcare provider’s recommendation was the strongest predictor of vaccine uptake. In the final multivariate model, receiving a provider recommendation significantly increased the likelihood of being vaccinated. High willingness supports this, with 67.3% of participants indicating that they would accept a vaccine if advised by their doctor. This highlights the irreplaceable role of trusted providers in countering hesitancy and the need for clinicians to be aware of vaccination guidelines and implement them in clinical practice.

Despite only 29.9% of participants reporting having contracted COVID-19, 64.5% received a COVID-19 vaccine, a rate significantly higher than the general adult population in South Africa, as reported in a global HIV cohort study.³⁴ This was likely influenced by extensive public health messaging and, potentially, vaccine mandates. Most participants cited self and family protection as their primary motivation to vaccinate. This demonstrates the power of coordinated campaigns and perceived severe threat in overcoming barriers.

PLWH remain disproportionately affected by VPDs, despite the availability of effective vaccines. The elevated burden of infections such as HBV, HPV, IPD, and meningococcal disease highlights a critical need for targeted immunisation strategies amongst PLWH. While global and regional guidelines exist, vaccine uptake among PLWH remains suboptimal, particularly in low- and middle-income countries like South Africa. The primary determinants of vaccine uptake identified were healthcare provider recommendation and awareness of vaccination. Key barriers include low health literacy (specifically awareness of one’s own viral load and ART status) and vaccine safety concerns. Strengthening vaccination programmes for PLWH through evidence-based policies, improved surveillance, and enhanced healthcare provider engagement is essential to reduce morbidity and mortality in this vulnerable population.