Nigeria is among the top ranked countries with high human immunodeficiency virus (HIV) burden worldwide, with about 3.1 million HIV-infected people and an estimated 215,000 HIV-related deaths in 2010 [
These studies have revealed that most HIV-infected patients in Nigeria present late to health care facilities with features of advanced HIV-related disease such as weight loss and chronic diarrhoea [
Currently, after more than eight years of availability of highly active antiretroviral therapy (HAART) in Nigeria, there is still a dearth of studies determining the morbidity and mortality patterns of hospitalised adult HIV/AIDS patients in relation to antiretroviral therapy (ART) status. Although few studies have evaluated the clinical and laboratory presentations of ART-related drug toxicities among out-patients [
A retrospective cohort analysis of routinely collected medical records of adult (>13 yrs) nonpregnant HIV/AIDS patients admitted into medical wards of Ahmadu Bello University Teaching Hospital (ABUTH) between January 2006 and December 2009 was undertaken using a standardized data extraction form. Only hospitalised patients with complete clinical details indicating diagnosis and clinical outcome were included. The demographic, clinical, and laboratory parameters of patients at the time of last hospitalisation were retrieved and analysed. Clinical diagnoses of prior hospitalisations during study period were documented when available. Based on ART status at last hospitalisation, patients were categorised into two groups, including group 1 (no previous ART experience) and group 2 (previous ART experience). Group 1 was defined as patients who had no prior history of receiving ART (based on patients account and available records) at the time of hospitalisation, while group 2 was defined as patients who had a prior history of receiving ART for whatever duration. Adherence to ART and use of Cotrimoxazole prophylaxis were not assessed as this information was not available in the admission medical records for most of the patients.
The study was undertaken in ABUTH, Zaria, a 700-bed referral hospital in Zaria, Kaduna state, Northern Nigeria. The HIV/AIDS treatment centre, situated within the hospital premises, offers comprehensive HIV treatment and care, including diagnosis of opportunistic infections, to adults, pregnant women, and children. Over 5000 HIV-infected nonpregnant adults are currently under care in the outpatient clinic, and sick patients are often admitted into the medical wards, managed by teams led by consultant physicians of various specialities. The HIV/AIDS treatment centre is supported by the US Presidents Emergency Plan for AIDS Relief (PEPFAR).
The diagnoses of HIV/AIDS-related events, ARV drug toxicities, and ART failure were based on WHO 2006 guidelines [
A case of IRIS was defined as a patient with unexpected deterioration in clinical condition with signs and symptoms of inflammation/infection soon after commencing ART (<6 months of regular ART). IRIS cases were classified as paradoxical or unmasking according to established clinical guidelines [
Aetiological diagnosis was based on compatible clinical presentation, response to therapy, or confirmatory investigations, all in accordance WHO 2006 guidelines for defining HIV/AIDS-related events [
The treatment of all opportunistic infections and use of HAART was according to the Nigerian National HIV adult treatment guidelines [
Survival outcomes (i.e., died or survived) were based on last contact with physician during hospitalisation. All discharged cases, cases of “discharged against medical advice” (DAMA), and transferred cases were classified as survived. Causes of death, filled into standardized death certification forms by attending physician at time of death, were discussed, reviewed, and validated at weekly mortality meetings. Unfortunately, permission for postmortem was not given for most patients in view of incongruous cultural/religious beliefs.
The ABUTH Institutional Review Board gave approval for the study.
Statistical analysis was undertaken using SPSS 17. Descriptive statistics were represented as median and interquartile range (IQR). Differences in variables by ART status were sought by Mann Whitney test and chi-square test as appropriate. Demographic and available laboratory data were compared according to survival status (i.e., died or survived). An unconditional binary logistic regression analysis checked for model fitness and interactions, and represented in odds ratio (OR) with 95% confidence interval (CI) was used to determine independent predictors of mortality. For regression analysis, we categorised age into young adults (15–45 yrs) and middle age/elderly (>45 yrs), PCV into severe anaemia (PCV < 24%,) and mild or no anaemia (PCV ≥ 24%), CD4 cell count into very severe immunosuppression (CD4 ≤ 50 cells/ul) and low or normal (CD4 > 50 cells/ul), symptom duration into acute (<30 days) and chronic (≥30 days), and hospital stay into ≤3 days and >3 days. Gender (male/female) and ART status (group 1/group 2) were also included in the regression analysis. Differences in survival between group 1 and 2 patients were represented in a Kaplan-Meir survival curve.
A total of 207 HIV/AIDS patients, representing 5.9% of 3464 adult medical admissions, and consisting of 152 (73.4%) group 1 and 55 (26.6%) group 2 patients, were studied. The demographic and clinical characteristics of patients according to ART status are shown in Table
Baseline characteristics of hospitalised HIV/AIDS patients in relation to antiretroviral therapy status.
Characteristics | No HAART |
Receiving HAART |
All patients |
---|---|---|---|
Age in years-median (IQR) | 35 (29, 43) | 40 (34, 48) | 36 (30, 45) |
Minimum–Maximum | 15–68 | 23–60 | 15–68 |
Gender |
|||
Male | 77 (50.7) | 32 (58.2) | 109 (52.7) |
Female | 75 (49.3) | 23 (41.8) | 98 (47.3) |
Marital status |
|||
Ever married | 120 (78.9) | 44 (80.4) | 164 (79.3) |
Never married | 32 (21.1) | 11 (19.6) | 43 (20.7) |
Occupation |
|||
Professionals/Civil servants | 37 (24.3) | 14 (25.5) | 51 (24.6) |
Unemployed housewives | 52 (34.2) | 12 (21.8) | 64 (30.9) |
Artisans | 20 (13.2) | 7 (12.7) | 27 (13) |
Students | 13 (8.6) | 6 (10.9) | 19 (9.3) |
Traders/Business | 11 (7.2) | 8 (14.5) | 19 (9.3) |
Farmer | 6 (3.9) | 2 (3.6) | 8 (3.9) |
Others | 13 (8.6) | 7 (12.7) | 20 (9.7) |
Risk factors for HIV |
|||
Heterosexual | 142 (93.4) | 50 (90.9) | 192 (92.8) |
Homosexual | 3 (2.0) | 2 (36.4) | 5 (2.4) |
Multiple sexual partners | 21 (13.8) | 13 (23.6) | 34 (16.4) |
Blood transfusion | 7 (4.6) | 3 (5.5) | 10 (4.8) |
Symptom duration in days | |||
Median (IQR) | 21 (14, 90) | 60 (14, 90) | 30 (14, 90) |
Hospital stay in days | |||
Median (IQR) | 14 (5, 24) | 14 (7, 30) | 14 (7, 28) |
Packed cell volume | |||
Median (IQR) | 27 (20, 33) | 24 (17, 34) | 27 (19, 34) |
PCV levels |
|||
|
22 (31.9) | 19 (48.7) | 41 (38%) |
24–29% | 20 (29.0) | 4 (10.3) | 24 (22.2%) |
|
27 (39.1) | 16 (41.0) | 43 (39.8%) |
Total WBC count | |||
Median (IQR) | 5.0 (3.7, 6.5) | 4.7 (3.9, 6.1) | 4.9 (3.7, 6.5) |
Platelet count-Median (IQR) | 246 (145, 331) | 230 (157, 271) | 233 (142, 310) |
CD4 cell count-Median (IQR) | 136 (5, 201) | 137 (56, 190) | 136 (56, 199) |
CD4 levels |
|||
|
11 (23.9) | 9 (23.7) | 20 (23.8%) |
50–200 | 23 (50.0) | 21 (55.2) | 44 (52.4%) |
201–350 | 7 (15.2) | 6 (15.8) | 12 (14.3%) |
|
5 (10.9) | 2 (5.3) | 7 (8.3%) |
NB—
No statistical significant differences were observed in demographic and laboratory variables between HAART experienced and ART naive patients (
The group 2 patients were older than the group 1 patients (40 versus 36 yrs,
In both ARV groups, majority were heterosexuals (92.8%), males (52.9%), and ever married (56.5%), and most were admitted with anaemia-PCV < 30% (60%) and severe immunosuppression CD4 ≤ 200 cells/ul (76.2%).
With regard to gender, median ages (IQR) of males were significantly higher than those for females in both group 1 (38 years (32, 46) versus 32 years (27, 38),
The clinical diagnoses of patients according to ART status are shown in Table
Clinical diagnoses of hospitalised HIV/AIDS patients in relation to antiretroviral therapy status and gender.
Diagnosis on presentation | ART status ( |
Total |
M/F | |
---|---|---|---|---|
No ART | Receiving ART | |||
Tuberculosis |
53 (34.9) | 16 (29.1) | 69 (33.3) | 0.87/1 |
Sepsis | 15 (9.2) | 6 (7.3) | 21 (10.1) | 1.1/1 |
Chronic diarrhoea | 8 (5.3) | 6 (7.3) | 14 (6.8) | 1.8/1 |
Typhoid fever | 8 (5.3) | — | 8 (3.9) | 1.7/1 |
Non-TB Pneumonia | 8 (5.3) | 3 (5.5) | 11 (5.3) | 0.4/1 |
Disseminated Kaposi’s sarcoma | 7 (4.6) | 1 (1.8) | 8 (3.9) | 2/1 |
Cerebral toxoplasmosis | 6 (3.9) | 1 (1.8) | 7 (3.4) | 2.3/1 |
Viral meningoencephalitis | 5 (3.2) | 1 (1.8) | 6 (2.9) | 0.7/1 |
Demyelinating polyneuropathy | 5 (3.2) | — | 5 (2.4) | 0.7/1 |
Cryptococcal meningitis | 4 (2.6) | 1 (1.8) | 5 (2.4) | 4/1 |
AIDS encephalopathy | 3 (2%) | — | 3 (1.4) | 2/1 |
Non-Hodgkin’s lymphoma | 3 (2%) | — | 3 (1.4) | 0.5/1 |
Acute gastroenteritis (Food poisoning) | 2 (1.3%) | 2 (3.6) | 4 (1.9) | 0.7/1 |
Steven Johnson's syndrome | 2 (1.3) | 2 (3.6) | 4 (1.9) | 1/1 |
Herpes zoster | 2 (1.3) | 1 (1.8) | 3 (1.4) | 0.5/1 |
Acute bacterial meningitis | 2 (1.3) | — | 2 (0.9) | 2/0 |
Wasting syndrome | 2 (1.3) | — | 2 (0.9) | 1/1 |
Acute viral hepatitis (HBsAg positive) | 2 (1.3) | — | 2 (0.9) | 1/1 |
HIV nephropathy | 2 (1.3) | — | 2 (0.9) | 1/1 |
Candidiasis (esophageal; disseminated) | 2 (1.3) | — | 2 (0.9) | 1/1 |
Vacuolar myelopathy | 1 (0.7) | — | 1 (0.5) | 0/1 |
Disseminated herpes simplex | 1 (0.7) | — | 1 (0.5) | 0/1 |
Severe malaria | 1 (0.7) | 1 (0.5) | 0/1 | |
Dilated cardiomyopathy | — | 1 (1.8) | 1 (0.5) | 0/1 |
Primary CNS lymphoma | 1 (0.7) | — | 1 (0.5) | 1/0 |
Glioblastoma multiforme | 1 (0.7) | — | 1 (0.5) | 1/0 |
Stroke-like state? cause | 3 (2) | 3 (5.5) | 6 (2.9) | 3/1 |
Primary liver cell carcinoma | 1 (0.7) | 1 (0.5) | 1/0 | |
Zidovudine-related severe anaemia | — | 4 (7.3) | 4 (1.9) | 2/1 |
Nevirapine-induced hepatoxicity | — | 2 (3.6) | 2 (0.9) | 2/0 |
Nevirapine-induced Steven’s Johnson syndrome | 2 (3.6) | 2 (0.9) | 2/0 | |
Hypertensive heart failure | — | 2 (3.6) | 2 (0.9) | 1/1 |
Hypertensive renal failure | 1 (0.7) | 2 (3.6) | 3 (1.4) | 0.5/1 |
Hypertensive haemorrhagic stroke | 1 (0.7) | 1 (0.5) | 0/1 | |
Peripartum cardiac failure | 1 (0.7) | 1 (0.5) | 0/1 |
NB—M/F is the ratio of number of male patients divided by female patients for each diagnosis in the total population.
Although a variety of clinical manifestations were observed, tuberculosis, sepsis, and chronic diarrhoea were the most common diagnoses in both ART groups. The various types of TB and other specific aetiological diagnoses are summarised in Table
Types of tuberculosis and specific aetiological diagnoses in patients in relation to antiretroviral therapy status.
Diagnoses and specific aetiologies | ART status |
Total | |
---|---|---|---|
No HAART | Receiving-HAART | ||
Types of tuberculosis | |||
Disseminated (mainly nodes and lungs) | 30 | 12 | 42 |
Pulmonary | 10 | 2 | 12 |
Spinal | 6 | — | 6 |
Meningitis | 5 | — | 5 |
Pericardial effusion | — | 1 | 1 |
Pleural effusion | 1 | 1 | 2 |
Peritonitis | 1 | — | 1 |
Causes of diarrhoea | |||
|
1 | — | 1 |
|
2 | — | 2 |
|
1 | — | 1 |
|
1 | — | 1 |
Unknown* | 3 | 6 | 9 |
Causes of pneumonia | |||
|
2 | 1 | 3 |
|
1 | — | 1 |
|
— | 1 | 1 |
Unknown* | 5 | 1 | 6 |
NB—*unknown implied that stool/sputum culture was negative or not done.
**Diagnosis of
The 9 paradoxical IRIS reactions included DTB (
The male to female ratio in diagnoses is shown in Table
There were 32 documented prior hospitalisations during study period, out of which 19 (59.3%) were in group 1 patients and 13 (30.7%) were in group 2 patients. Group 1 patients had prior hospitalisations for pulmonary tuberculosis (
Of the 207 admitted patients, 112 (54.1%) were discharged, 27 (13%) were “DAMA.” 2 (1%) were transferred and 66 (31.9%) died. The 66 cases of mortality consisted of 47 (30.9%) of 152 group 1 and 19 (34.5%) of 55 group 2 patients.
The various causes of death are listed in Table
Causes of death in hospitalised HIV/AIDS patients in relation to antiretroviral therapy status.
Causes of death | ART status ( |
Total |
|
---|---|---|---|
No HAART | Receiving-HAART | ||
(1) DTB | 14 (29.8) | 6 (31.6) | 20 (29.9) |
(2) PTB with respiratory failure | 3 (6.4) | 1 (5.3) | 4 (6.0) |
(3) TB meningitis | 2 (4.3) | — | 2 (3.0) |
(4) Bone marrow TB | 1 (2.1) | — | 1 (1.5) |
(5) Sepsis | 9 (19.1) | 4 (21.1) | 13 (19.7) |
(6) Viral meningoencephalitis | 2 (4.3) | 1 (5.3) | 3 (4.5) |
(7) Cryptococcal meningitis | 2 (4.3) | 1 (5.3) | 3 (4.5) |
(8) Disseminated Kaposi’s sarcoma | 2 (4.3) | 1 (5.3) | 3 (4.5) |
(9) Non-Hodgkin’s lymphoma | 2 (4.3) | — | 2 (3.0) |
(10) Hypovolaemic shock from gastroenteritis | 2 (4.3) | — | 2 (3.0) |
(11) Stroke-like state? cause | 2 (4.3) | 1 (5.3) | 3 (4.5) |
(12) Acute bacterial meningitis | 1 (2.1) | 1 (5.3) | 2 (3.0) |
(13) Severe pneumonia | 1 (2.1) | 1 (5.3) | 2 (3.0) |
(14) Hepatic failure | 1 (2.1) | 1 (5.3) | 2 (3.0) |
(15) Disseminated candidiasis | 1 (2.1) | — | 1 (1.5) |
(16) PLCC | 1 (2.1) | — | 1 (1.5) |
(17) Pulmonary embolism-Vacuolar myelopathy | 1 (2.1) | — | 1 (1.5) |
(18) End stage renal failure | 1 (2.1) | 1 (5.3) | 2 (3.0) |
Differences in clinical variables in relation to outcome (died or survived) are summarised in Table
Comparisons of demographic and clinical variables in relation to survival outcome of HIV/AIDS patients.
Variables | Survival status |
|
|
---|---|---|---|
Died | Survived | ||
Age in years | |||
Median (IQR) | 38 (30, 46) | 35 (30, 45) | 0.29 (NS) |
Gender ( |
|||
Male | 42 (38.5%) | 67 (61.5%) | 0.03 |
Female | 24 (24.5%) | 74 (75.5%) | |
Symptom duration in days— | |||
Median (IQR) | 60 (15, 120) | 30 (14, 90) | 0.018 |
Hospital stay in days | |||
Median (IQR) | 7 (3, 18) | 17 (10, 31) |
|
PCV | |||
Median (IQR) | 22 (16, 29) | 28 (20, 35) | 0.012 |
Platelets count | |||
Median (IQR) | 129 (85, 252) | 242 (186, 312) | 0.016 |
CD4 cell count | |||
Median (IQR) | 45 (21, 237) | 140 (60, 194) | 0.18 (NS) |
ART duration (yrs) | |||
Median (IQR) | 0.25 (0.17, 3.0) | 0.8 (0.28, 2.0) | 0.67 (NS) |
NB—NS: not significant; PCV: packed cell volume; IQR: interquartile range.
The predictors of mortality are summarised in a univariate and a multivariate analysis as shown in Table
Variables associated with mortality in hospitalised HIV/AID patients.
Variable* | Univariate | Multivariate | ||
---|---|---|---|---|
OR (95% CI) |
|
AOR (95% CI) |
|
|
15–45 yrs | 0.84 (0.54–1.33) | 0.47 | 0.85 (0.12–6.22) | 0.87 |
Male | 1.57 (1.03–2.39) | 0.03 | 5.3 (0.96–28.9) | 0.06 |
Receiving ART | 1.12 (0.72–1.73) | 0.62 | 4.8 (0.8–28.4) | 0.09 |
Symptom duration |
1.42 (0.90–2.23) | 0.13 | 2.2 (0.42–11.8) | 0.35 |
Hospital stay |
2.71 (1.94–3.79) |
|
13.8 (1.1–178) | 0.045 |
CD4 count |
3.2 (1.28–8.0) | 0.012 | 2.6 (0.5–13.8) | 0.27 |
PCV |
2.1 (1.15–3.87) | 0.015 | 5.7 (1.2–26.7) | 0.029 |
NB—*Variable lists are all reference values. OR: odds ratios; AOR: adjusted odds ratio; CI: confidence interval. [Model goodness of fit-
The Kaplan-Meir survival curves of both ART groups shown in Figure
Survival after hospitalisation in relation to antiretroviral status—no significant difference in survival rates were observed between both ART groups (Log rank
The results of this study has shown that in the current era of HAART in Nigeria, majority of the hospitalised HIV-infected patients are heterosexuals of young productive age and that most of the newly diagnosed HIV-infected patients as well as patients receiving ART are hospitalised on account of AIDS-defining illnesses characterised by severe immunosuppression and anaemia. These findings possibly reflect late HIV diagnosis and delay in initiation of HAART. It is worrisome that even with the provision of free ARV drugs in many parts of Sub-Saharan African many HIV/AIDS patients from this region still suffer from advanced HIV-related diseases [
Although the morbidity and mortality of HIV/AIDS in Nigeria are known to predominantly affect females [
In studied participants, we observed a variety of HIV-related and unrelated manifestations, but tuberculosis, followed by sepsis and chronic diarrhoea, were the most common causes of morbidity in both groups of patients. This spectrum of clinical presentations is similar to that reported in an earlier study of hospitalised HIV/AIDS patients in our region in the pre-HAART era [
Possibly reflecting the benefits of HAART in reducing rates of hospitalisation [
Although some differences in study design exist, the overall mortality rate of 31.8% observed in our study population is comparable to the mortality rates of 26 to 40% reported in other studies of hospitalised HIV/AIDS patients during the HAART era from Nigeria [
In our patients, PCV was found to be independently associated with mortality with a six-fold risk of mortality in patients with severe anaemia. This finding corroborates studies from other developing countries [
There are limitations to our study. First, since the study was retrospectively designed, detailed clinical and laboratory variables were not available for all patients. However, we believe the missing data did not significantly affect the major outcomes of the study since our findings were comparable to those within and outside Nigeria. Data quality can be improved by future prospective studies from Nigeria to clarify the independent associations, if any, between variables such as CD4 and platelet counts, and mortality of hospitalised HIV/AIDS patients in Nigeria, as shown by studies from other parts of Africa [
Second, we could not confirm the causes of deaths in most patients because of lack of permissions for autopsies. However, the listed causes of death were standardized and further validated during mortality reviews. The aetiological causes of sepsis could also not be confirmed by positive blood cultures possibly because most patients often practise self-medication or receive antibiotics elsewhere before hospitalisation, making cultures negative. However, culture of microorganisms such as mycobacteria and other atypical microorganisms reported to cause sepsis in HIV-infected patients [
This study undertaken in a major tertiary hospital in Northern Nigeria during the HAART era has shown that majority of hospitalised HIV/AIDS patients are heterosexuals of young productive age, males and newly diagnosed HIV-infected patients with no previous ART experience. Most patients were admitted on account of AIDS defining illness such as disseminated TB and sepsis, with features of severe immunosuppression and anaemia. The study data also revealed that mortality was high due to late presentation and advanced disease, and that there was a six-fold risk of mortality in those with severe anaemia. To combat the high morbidity and mortality associated with HIV/AIDS in developing countries such as Nigeria, strategies for early HIV diagnosis, prompt initiation of HAART, prevention of TB co-infection in HIV, and early recognition of danger signs such as low PCV must be initiated, implemented, and strengthened as necessary.
D. Ogoina conceived the report and wrote the paper. All authors were involved in data collection, revised the final draft, and gave approval for submission.
The authors have no competing interests to declare.
The authors acknowledge all staff of Department of Medicine and Haematology ABUTH, Zaria, as well as staff of ABUTH adult HIV clinic who were actively involved in providing care and treatment to the HIV/AIDS patients reported in this study.