INTRODUCTION
South Africa has the largest Human Immunodeficiency Virus (HIV) epidemic in the world. It therefore accounts for a large proportion of the global burden of the HIV pandemic, with 19% of the worldwide population of PLWH, 15% of new infections and 11% of the Acquired Immunodeficiency Syndrome (AIDS)-related deaths.(1) In addition, South Africa has the largest antiretroviral treatment (ART) programme in the world, accounting for a fifth of all persons worldwide on ART.
Since 2004, there has been a substantial improvement in access to ART in South Africa. There has been an evolution of the National HIV Treatment Guidelines with the change of ART eligibility criteria from a CD4 cell count < 200 cells/µl in 2004, to treatment for all with a universal test and treat (UTT) policy introduced in September 2016. (2,3)
The proportion of patients newly diagnosed with advanced HIV is decreasing, showing some success of UTT.(4) However, 15 years since the ART rollout, challenges persist. South Africa is still experiencing gaps in the cascade of HIV care that result in complications and death from TB and AIDS-related illnesses (5), and hospitals still admit a large number of patients with HIV-related conditions.(6) From June 2012 to October 2013, almost a decade into the ART era in the country, over 60% of all medical admissions in a district hospital in Cape Town were HIV-related.(7) A study in 2016, conducted at a regional public-sector hospital in Johannesburg, found that nearly half of the medical admissions were PLWH, and the mortality rates were higher among PLWH compared to those patients who are HIV-negative. (6)
Under the strategy of UTT, the HIV epidemic in South Africa has matured and access to ART has increased. As such, this is an appropriate time to review and compare current data with that predating UTT. Thus, following the introduction of the policy of UTT, the aim of this study was to assess the prevalence of PLWH admitted to a general medical ward of a tertiary public hospital in a large urban city in South Africa, and additionally to determine the medical indication for their admission, adherence to ART, their admission CD4 counts as well as their employment status at time of admission.
METHODS
The study was a clinical audit of general medical patient admissions to Helen Joseph Hospital, in Johannesburg South Africa, a public-sector tertiary institution, which provides tertiary level healthcare to a regional population of approximately 1 million people. The study population included all medical patients admitted to a single medical unit over a 5 month period from September 2018 to January 2019. ART was freely available to all patients during this period.
Ethical approval for the study was obtained from the University of the Witwatersrand's Human Research Ethics Committee. Patients gave informed consent prior to their results being accessed. Data was collected from all patients during the study period. Descriptive statistics were performed for all patients. Results were reported as mean ± standard deviation (SD) or median values with interquartile ranges (IQRs) for continuous variables, and frequencies and percentages for categorical variables as appropriate.
DEFINITIONS
Treatment naïve is defined as HIV infected patients who have never been on ART.
Currently on ART with previous interruption is classified as PLWH and on ART at admission but having interrupted therapy for more than 5 days previously.1
Treatment interrupted describes HIV infected patients not on ART for at least 5 days at admission but on ART previously.
Virological failure was defined as per the World Health Organisation (WHO) definition: A plasma viral load above 1000 copies/ mL on two consecutive occasions 3 months apart while on ART, despite adherence support (9). For the purposes of this report and because patients were only assessed once during this study, those on ART were deemed to be failing treatment if found to have a viral load above 1000 copies/mL on only a single occasion namely at the time of their admission.
Tuberculosis (TB) infection was defined as a positive GeneXpert or TB culture on sputum, cerebrospinal fluid, pleural fluid, fine needle aspiration of lymph nodes, ascitic fluid or a positive urine lipoarabinomannan (LAM) test.
RESULTS
A total of 794 patients were admitted to our medical unit during the course of the study (Figure 1). Of the 794 patients, 337 patients were found to be HIV-infected (42.4%) while 214 patients tested negative for HIV and 243 patients were not tested for HIV status on admission (status unknown). Of the HIV-infected patients, 246 (73%) were already known to be HIV-infected prior to admission while 91 (27% ) were newly diagnosed with HIV infection on admission.
Demographics
The demographic characteristics of the study population are summarised in Table 1. The mean age of the HIV infected patients at admission was 40.7 years (SD 12.3), while that of the HIV-negative was 49.7 years (SD 37.1) and those not tested was 57.4 years (SD 36.8). The mean age of newly diagnosed HIV infected patients was 39.8 (SD 10.9) years. Those on treatment had a higher mean age of 43.3 years (SD 12.4), while that of patients who had interrupted treatment was 40 years (SD 12.4). The HIV-infected, ART naïve patients had a mean age of 35.3 years (SD 12.4)). Males accounted for 51% of all HIV infected patients and 59.3% of newly diagnosed PLWH. 52% of patients who had interrupted ART were male. The majority of admitted PLWH were unemployed (58.4%) compared to only 36.3% of HIV-negative patients or patients that were not tested.
Demographic characteristics of HIV-negative, HIV status unknown and HIV infected patients admitted
| HIV tested negative (Total n = 214) | HIV status unknown or not tested (Total n = 243) | HIV positive (Total n = 337) | Newly Diagnosed HIV infected (Total n = 91) | HIV positive on ART (Total n = 191) | On ART at admission with previous interruption (Total n = 48) | ART naïve at admission (HIV infected) (Total n = 26) | Treatment Interrupted (Total n = 29) | |
|---|---|---|---|---|---|---|---|---|
| Mean Age, years. | 49.7 (SD 37.1) | 57.4 (SD 36.8) | 40.7 (SD 12) | 39.8 (SD 10.9) | 43.3 (SD12.4) | 40 (SD 12.4) | 35.3 (SD 12.4) | 37.9 (SD 12.4) |
| Male | n = 109 (50.9%) | n = 104 (42.8%) | n = 172 (51%) | n = 54 (59.3%) | n = 61 (43.7%) | n = 27 (56.2%) | n = 15 (57.7%) | n = 15 (52%) |
| Unemployed (% of Total | 43% (n = 92) | 30.4% (n = 74) | 58.4% (n = 197) | 61.5% (n = 56) | 52.3% (n = 100) | 60% (n = 29) | 69.2% (n = 22) | 75.8% (n = 22) |
ART History
At the time of admission, 191 (77.6%) patients previously known to be HIV infected were on ART. Of these patients, 48 (25%) had previously interrupted treatment. Almost 12% of patients known to be HIV infected currently had interrupted treatment (i.e. stopped taking ART for at least 5 consecutive days). Of the patients previously known to be HIV infected, 10.5% had not yet initiated treatment despite knowing their HIV infected status (ART naïve).
CD4 count and viral load
Of the 91 persons newly diagnosed with HIV, a CD4 counts and viral loads were not available for 10 patients and 28 patients respectively. In the already known HIV infected group, 17 (7%) did not have their CD4 count available and 36 (14.6%) did not have a viral load test.
Among all HIV infected patients, the median CD4 cell count was 67 cells/µl (IQR 23-259.5) and the median viral load was 31,400 copies/ml (IQR 96.5 - 421,000). Among newly diagnosed HIV infected admissions, the median CD4 count was 44 cells/µl (IQR 13-108) and the median viral load was 438 000 copies/ml (IQR 180,250- 1,255,000). Patients who had interrupted ART had a median CD4 count of 92 cells/µl (IQR 16-147.5) and median viral load of 957.5 copies/ml (IQR 13,350 – 404,500). (Table 2).
Of all HIV infected admissions 26.1 % (88/337) had viral loads greater than 1000 copies/mL, with 32.9% (n=47/143) of all patients on ART having viral loads >1000copies/mL and 85% (41/48) of patients who had previously interrupted treatment having viral loads >1000copies/mL.
Laboratory characteristics of HIV infected patients collected on admission
| All HIV infected | Newly Diagnosed HIV infected | On Treatment without interruption | Currently on ART with previous interruption | ARV naïve (known HIV positive not on ART) | Interrupted ART | ||
|---|---|---|---|---|---|---|---|
| CD4 cell count (cells/µl) | Median | 67 | 44 | 100 | 100 | 100 | 92 |
| IQR | 23–259.5 | 13–108 | 30.2–350.6 | 28–350 | 31–354.5 | 28–351 | |
| Viral Load (copies/ml) | Median | 31 400 | 438 000 | 862 | 957.5 | 778 | 957.5 |
| IQR | 96.5–421000 | 180 250–1 255 000 | 20–123 000 | 20–133250 | 20–105750 | 20.8–139750 | |
Indications for admission and co-morbid illnesses.
The most frequent indication for admission among HIV infected patients was TB, (n=76/337 (22.6%). Of the admitted HIV-positive patients, 59 (17.5%) had AIDS-defining illnesses. These included; Pneumocystis jirovecci pneumonia (n=22), cryptococcal meningitis (n=11), cryptosporidium gastroenteritis (n=2), disseminated herpes simplex infection (n=2), disseminated cytomegalovirus infection (n=1), Mycobacterium avium complex infection (n=2) and AIDS-defining malignancies (n=8) (Figure 2).
Co-morbid illnesses among HIV infected patients at admission
Note: These co-morbid diseases were either diagnosed on admission or noted to have been diagnosed previously. Non-communicable diseases include: diabetes mellitus, hypertension, chronic obstructive pulmonary disease, heart disease.
Non-communicable diseases (NCDs), which comprised of diabetes mellitus, hypertension, chronic obstructive pulmonary disease and heart disease, accounted for 19 (5.6%) admissions of HIV infected patients compared to 149 (32.6%) of patients whose HIV status was negative or unknown. The relative risk of being admitted with a NCD when comparing HIV infected to HIV-negative/not tested patients was 0.2 (95% CI: 0.1 - 0.3).
Interruption of ART
A quarter of patients on ART had previously interrupted treatment (Table 3).The most frequent reason for treatment interruption was “no reason”, while the next most common reasons were forgetting to take treatment, denial of status despite previous documentation, and a lack of understanding with regard to HIV and its management. Social reasons accounted for 29.9% of reasons for interrupting treatment. These included being unable to afford travel to a clinic, food insecurity, child reliant on a caregiver to obtain medication and social influence. Other reasons for ART interruption included drug-related side effects in 8 patients and social stigma in another 8 patients (10.3 %).
Reasons given for interrupting ART among HIV infected patients admitted to hospital (n=77)*
| Reasons for Interrupting | Number of patients |
|---|---|
| No Reason | 18 |
| Lack of insight into treatment | 4 |
| Unable to afford transport to clinic | 10 |
| Forgets | 4 |
| Denial | 5 |
| Travel related/travelling for work | 9 |
| Drug side-effects | 8 |
| Social stigma | 8 |
| Depression/Psychosis | 5 |
| Food insecurity | 2 |
| Child dependent on parent to collect tablets | 2 |
| Traditional healer advising to stop | 1 |
| Clinic stock-out | 1 |
* A total of 77 patients include those currently on ART with previous interruption and those admitted while having interrupted ART.
DISCUSSION
This study found that the proportion of PLWH admitted to the medical wards of a large public hospital in South Africa, over a five month period in 2018/2019, was high (42%) despite increased access to ART in recent years. Of interest is that more than a quarter (27%) of patient admissions even in the era of UTT, were newly diagnosed at the time of admission. Disappointingly close to half of those on ART were not virologically suppressed.
Newly diagnosed patients who were ART-naïve and often extremely ill on admission, had lower median CD4 counts of only 44 cells/µl. Patients on treatment also had a low median CD4 count of 100 cells/µl. This confirms that admission median CD4 counts of hospitalised patients, when compared with studies completed prior to the implementation of UTT in South Africa, show little change.(6,7,10–12) Despite the current UTT programme, low CD4 counts in this group of HIV-infected patients probably explains their susceptibility to AIDS-defining conditions and the likelihood of admission to hospital. Changes in absolute CD4 cell count can also be affected by acute illness, co-morbidities and drugs such as systemic corticosteroids or chemotherapy. As a result, it is important to monitor changes in the CD4 cell count over time as opposed to using single readings. (13)
In the current study, TB and other AIDS-defining illnesses were the primary conditions that resulted in hospital admission among PLWH. (6,7) Tuberculosis and other AIDS-defining illnesses contributed to high hospital case-loads in the period before the policy of UTT (14), but the current study highlights the persistence of these illnesses as a large burden on the health system despite increased ART access.
The majority (58%) of HIV infected patients admitted in this study were unemployed. This highlights a possible association of unemployment with poor ART outcomes and late presentation. Thus alleviation of poverty and unemployment is likely to increase successful outcomes but this requires further investigation.
This study also found that social reasons for interrupting treatment such as transport costs and work-related travel play a large role as highlighted by earlier research (15,16). Major social interventions would need to be implemented to address these issues. There is growing evidence that differentiated service delivery may be a successful approach to tackle some of these issues. These interventions include adherence support clubs, contraception and family planning, service delivery to specific high risk groups as well as more decentralised centres of care. (5,8,17)
A quarter of patients on ART had previously interrupted their treatment and almost 10% of all HIV infected patients had interrupted treatment completely at the time of admission. The most common reason for treatment interruption in this study was “no reason”. This was the response given by patients in their own words when asked about why they had interrupted treatment. This indicates a concerning disengagement from care as patients were not willing to engage with a healthcare worker as to the reason for their treatment interruption. Possible reasons for this could be stigma around HIV diagnosis, distrust of healthcare workers, language barriers, denial and unwillingness to disclose social and monetary barriers to accessing care. Of note is that 10.5% of all HIV admissions in the study already had a positive status on admission but had not yet initiated treatment, again showing an alarming failure of linkage to care. This is in keeping with a trend that there are still an appreciable number of patients who should have started ART but have not yet done so (4). This again may be due to a number of factors including patient factors such as stigma, costs of travel to and from clinics and heath care provider factors such as stock outs, long waiting times, staff shortage and inadequate communication between health professionals and patients (15). This together with the high treatment interruption rate and large numbers of patients with unsuppressed viral loads shows that the successes made in treating regardless of CD4 count are being countered by a significant proportion of patients that present again due to interrupting ART, resulting in virological failure.(4) The large scale public health response to the Covid-19 pandemic can perhaps provide a way forward in finding solutions to combat these issues with improved access to health care services and systems to reach millions of South Africans in a short period of time. Media campaigns, public and private co-operation and large vaccination drives may provide the infrastructure and logistical support needed to improve HIV management.
A worryingly large number of patients were not tested for HIV on admission to hospital. Reasons for this are speculative but possibly include patients’ unwillingness to consent to testing, patients unable to consent due to medical illness and patients possibly were not tested on admission but tested later during their hospital stay.
Prior to the policy of test and treat regardless of CD4 count and universal access to ART, up to 60% of medical admissions were due to HIV-related illnesses, up to 50% of patients on ART were not virally suppressed, high numbers of patients known to be HIV infected were still ARV naive and large numbers of patients were newly diagnosed on admission (6,7). Some areas in the country are showing success in moving towards the UNAIDS 90-90-90 targets (20,25). However, this study shows that the situation remains minimally changed within a public hospital setting, despite the UTT policy.
LIMITATIONS
Limitations of this study are that it is a single centre cross sectional study conducted over a short time span. Only admissions to a single medical unit was sampled. Data was collected from September to January and thus there may be seasonal variation in indications for admission. Indications for admission were based on initial assessment and not a discharge diagnosis. Not all admitted patients were tested for HIV, thus possibly underestimating the prevalence of the HIV-positivity rate in the study cohort.
CONCLUSION
In conclusion, the proportion of medical patients, who are HIV infected and admitted to public hospitals in South Africa remains high even in the era of UTT. The indications for admission among HIV infected patients have remained unchanged despite the new ART policy. There has also been little change in the median CD4 counts of patients admitted to hospitals compared to before the universal test and treat era and rates of virological failure remain similar. Additional interventions are needed to provide solutions. Improvements may only ensue with a reversal of poverty and unemployment of many of our patients. As HIV treatment is the purview of primary care, the assessment and strengthening of primary care clinics providing HIV treatment may be necessary.