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World Health Organization’s Stage 4 Conditions Among Adults Accessing Outpatient HIV Care: A Retrospective Cohort Study in Kisumu, Kenya

Owiti, Patrick O. MD; Penner, Jeremy MD, MHSc, DTM&H; Oyanga, Arbogast BScIT; Huchko, Megan MD, MPH; Onchiri, Frankline M. MS, PhD; Cohen, Craig MD, MPH; Bukusi, Elizabeth A. MD, MMed, MPH, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 1st, 2014 - Volume 65 - Issue 4 - p e152–e155
doi: 10.1097/QAI.0000000000000020
Letters to the Editor

Centre for Microbiology Research, Research Care and Training Program, Kenya Medical Research Institute—FACES, Kisumu, Nyanza Kenya

Supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through cooperative agreement (#1U2GPS001913) from the U.S. Centers for Disease Control and Prevention, Division of Global HIV/AIDS. The findings and conclusions in this letter are those of the authors and do not necessarily represent the official position of the CDC.

The authors have no conflicts of interest to disclose.

To the Editors:

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Opportunistic infections (OIs) are the main cause of morbidity and mortality in patients with HIV-1 infection throughout the world, particularly among patients who have not had access to anti-retroviral therapy (ART) and other HIV care services.1–3 Among patients taking ART, OIs can present when the immune system starts to recover, also known as immune reconstitution inflammatory syndrome.4,5 Also, some patients do not have a sustained response to ART due to the lack of adherence to medications, development of drug resistance, or suboptimal therapeutic regimens.1 Therefore, OIs continue to cause substantial morbidity and mortality even after the initiation of ART.

The World Health Organization (WHO) developed HIV clinical staging criteria based on OIs to standardize disease severity classification in the absence of virologic or immunologic measurements.6,7 Diagnosis of WHO stage 4 conditions remains important in the ART era to (1) help determine timing of ART initiation and (2) treat OIs to reduce morbidity and mortality. There are no published data from Kenya that quantify the burden of WHO stage 4 conditions that persist in the ART era and continue to negatively impact patient survival. Therefore, we set out to determine the prevalence and gender distribution of WHO stage 4 conditions among patients enrolled in a large periurban HIV clinic in western Kenya.

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We performed a retrospective review of adult patients who enrolled into care in a comprehensive outpatient HIV clinic between March 2005 and July 2008 and analyzed the frequency of WHO stage 4 conditions.

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The Family AIDS Care and Education Services (FACES) program, a collaboration between the Kenya Medical Research Institute and University of California, San Francisco, pioneered a family model of HIV prevention, care, and treatment in Nyanza Province and Nairobi, Kenya.8 This study was conducted at Lumumba Health Centre (LHC), which is one of FACES' largest outpatient HIV clinics in Kisumu, Nyanza Province. Nyanza Province has an HIV prevalence of 15.3%, which is more than twice the national prevalence of 6.3%.9 LHC has the capacity for on-site laboratory tests, including complete blood count, serum chemistries, CD4+ cell count assays, rapid plasma reagin, and serum cryptococcal antigen testing. Tissue biopsies for cytology and chest radiographs are available within Kisumu and are routinely paid for with program funds. Additional tests such as ultrasound, computed tomography scans, and endoscopy are available, but coverage depends on the availability of extra program funds or the patients' ability to pay. ART is available at no cost to patients who qualify based on WHO stage and/or CD4 count, following the Kenya national guidelines.10 Patients attending LHC for HIV care are staged according to WHO criteria as part of their enrollment assessment and reassessed at every follow-up visit.

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Data Sources

The HIV clinic at LHC has an electronic medical record system (EMRS) that captures important patient-level demographic and clinical variables at each clinic visit. At every visit, patient encounters are documented using standardized clinical forms, after which the information is entered into the EMRS. Information collected using patient encounter forms includes demographic characteristics, such as age and gender, ART status, and clinical variables, such as WHO stage and staging criteria, and laboratory test results. In September 2009, we used the EMRS database to identify all adult patients (age, >15 years old) who were enrolled into care between March 2005 and July 2008. Out of these newly enrolled patients, we identified those with WHO stage 4 conditions at enrollment or subsequent visits. We obtained data on CD4+ cell count at enrollment, gender, age, and status in care [dead, alive in care, transferred out, or lost to follow-up (LFU)] at the time of data abstraction. The patient files were reviewed to confirm diagnosis and abstract missing variables. For patients who had not attended the clinic for 3 or more months, a community health worker called or attempted a home visit to determine their current status. If the community health worker was not able to locate them or receive a reliable report of their status, then they were classified as LFU.

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Statistical Methods

Data from the EMRS were exported into an Excel (Microsoft, Inc, Redmond, WA) spreadsheet. Data abstracted from manual chart reviews were entered into a standardized data abstraction tool, then transferred to the spreadsheet. Bivariate analysis was performed to examine the association between various WHO stage 4 conditions and age, gender, and CD4+ cell count. The χ2 or Fisher exact tests were used for categorical variables, and the Student t test was used to compare continuous variables. Data were analyzed using STATA version 11.0 (StataCorp, College Station, TX). A value of P < 0.05 was considered significant.

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Ethical Considerations

The FACES program obtained ethical approval from the Kenya Medical Research Institute Ethical Review Committee and the University of California, San Francisco Committee on Human Research to utilize routinely gathered retrospective medical information for the evaluation and dissemination purposes, including the data abstracted for this study. To protect patient privacy, all data were deidentified and delinked with patient identifiers.

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Of the 5784 adult patients enrolled during the study period, 437 (7.6%) had a WHO stage 4 diagnosis during the study period at enrollment and follow-up, of which 260 (59.5%) were women. Among all women enrolled into care, 6.7% had a WHO stage 4 diagnosis compared with 9.3% among all enrolled men (P < 0.001). The mean age of women was 34.7 years (SD, 9.0) compared with 37.2 years (SD: 8.4) for men. The median CD4+ cell count at enrollment was 84 cells per microliter (interquartile range: 31–191), and 325/423 (76.8%) patients had a baseline CD4+ cell count below 200 cells per microliter. Of the 437 patients with WHO stage 4 diagnosis, 427 (97.7%) patient files were found and reviewed. These 427 patients contributed 483 WHO stage 4 conditions to the analysis as 56 patients had 2 conditions.

Of the 427 patients, 367 (85.9%) were initiated on ART during the study period; 346 of the 367 who had been initiated on ART had dates recorded for ART initiation and the WHO stage 4 diagnosis. Of the 346 patients, 127 (36.7%) had started on ART before the WHO stage 4 diagnosis, 34 (9.8%) started ART on the day of their WHO stage 4 diagnosis, and 185 (53.5%) started ART after the WHO stage 4 diagnosis. Of the 127 patients diagnosed with a WHO stage 4 diagnosis after ART initiation, 78 (61.4%) had the diagnosis within 6 months of ART initiation.

At the end of the study period, 253 (59.2%) were active in care, 60 (14.0%) were confirmed dead, 28 (6.6%) had transferred out to other HIV clinics, and 86 (20.1%) were LFU.

The most common conditions in order of frequency were esophageal candidiasis, extra pulmonary tuberculosis, HIV wasting syndrome, Kaposi's sarcoma (KS), and cryptococcal meningitis (Table 1). Esophageal candidiasis was significantly more frequent among women with WHO stage 4 conditions than among men (P = 0.029), and KS was more frequent among men (P < 0.001). When analyzing frequency of WHO stage 4 conditions based on a CD4+ cutoff of 100 cells per microliter, only esophageal candidiasis was significantly associated with CD4+ count ≤100 cells per microliter (P = 0.003) (data not shown).



Among the 56 patients with more than 1 WHO stage 4 condition, the most frequent combination was esophageal candidiasis and HIV wasting syndrome [15 (26.8%)]. Pleural effusion was the most frequent type of extra pulmonary tuberculosis (58.8%), whereas cutaneous KS involving the lower limbs was the most frequent presentation of KS (64.4%) (data not shown).

Those initially diagnosed with esophageal candidiasis, HIV wasting syndrome, KS, and extra pulmonary tuberculosis contributed most to the number of deaths (data not shown).

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Our study found that 7.6% of our patients had a WHO stage 4 diagnosis. We also found a higher proportion of WHO stage 4 conditions among men compared with women enrolled in care, a finding consistent with 2 other studies in east Africa which found that at enrollment, men were more immunocompromised compared with women.11,12 This could be attributed to the poor health seeking behavior of men delaying or avoiding enrollment in care even after they know their HIV status.13–15

We found that esophageal candidiasis was more common among women. This gender distribution is consistent with other HIV-positive cohorts.16,17 KS was more common among men, which is consistent with studies among non–HIV-positive cohorts,18,19 and among HIV-positive patients.16

The major limitation of our study was reliance on clinical diagnosis for many of the WHO stage 4 conditions of interest. Although this may contribute to an underestimation or overestimation of the disease prevalence for certain conditions, it is representative of how patients are diagnosed and treated in similar resource-limited settings.

This study identified the most common WHO stage 4 conditions in a periurban HIV clinic in western Kenya. These findings can provide guidance to HIV programs for prioritizing resources to ensure adequate diagnosis and management of these conditions.

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The authors acknowledge the leadership of the Director of KEMRI, Prof Solomon Mpoke and the technical support provided by the CDC Kenya Branch Chief, Dr Lucy Ngang'a and our CDC Technical Manager, Dr Evelyn Ngugi, and the staff of FACES Lumumba HIV Clinic for their dedicated service to patients.

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