|Year : 2019 | Volume
| Issue : 3 | Page : 293-297
A cross-sectional study of cytomegalovirus retinitis in HIV-1 infected adults in Nigeria
MA Adeiza1, AG Habib2
1 Department of Medicine, Infectious Disease Unit, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna, Nigeria
2 Department of Medicine, Infectious and Tropical Disease Unit, College of Health Sciences, Bayero University/Aminu Kano Teaching Hospital, UngwaUku, Kano, Nigeria
|Date of Acceptance||10-Dec-2018|
|Date of Web Publication||6-Mar-2019|
Dr. M A Adeiza
Department of Medicine, P.M.B 06, Ahmadu Bello University Teaching Hospital, Shika-Zaria, Kaduna State
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Cytomegalovirus (CMV) retinitis is one of the most important opportunistic infections in HIV-infected patients in developing countries before the introduction of highly active antiretroviral therapy. In Nigerian and African HIV populations, CMV retinitis is under-reported. Patients and Methods: In a cross-sectional study, 250 HIV-infected adults ≥18 years were recruited by systematic random sampling from March to August 2013. Using a structured questionnaire, information was obtained on socio-demographic characteristics and symptoms of visual impairment. HIV disease was staged according to the WHO clinical staging, and CD4+ T-lymphocyte count was measured. Participants with symptoms of impaired vision and/or CD4+ T-lymphocyte count <50 cells/μL had indirect ophthalmoscopic examination of the retina to detect CMV related eye lesions. Results: Two hundred and fifty adults were HIV-infected, out of which 114 (46%) were males and 136 (54%) were females. The mean age of study participants was 35 years. History of impaired vision was reported by 21 (8.4%) of participants. The right eye was involved in 7 (33%), the left eye in 4 (19%), and both eyes in 10 (48%) of participants. The predominant symptoms were blurred vision 9 (43%), floaters 9 (43%), and blindness 3 (14%). Among participants who had indirect ophthalmoscopy, 3 (1.2%) had characteristic retinal changes suggestive of CMV retinitis. Two (67%) of patients with CMV retinitis were females and 1 (33%) was male. Mean CD4+ count was 25.33 ± 14.19 and all were WHO HIV clinical stage 4 with death occurring within 6 months of diagnosis. Conclusion: CMV retinitis though rare is associated with advanced HIV disease and attendant morbidity and mortality. We recommend integration of CMV diagnostic services and ophthalmological services as routine in HIV care and treatment programs in Nigeria targeted toward high-risk patients.
Keywords: Cytomegalovirus, HIV, Nigeria, retinitis
|How to cite this article:|
Adeiza M A, Habib A G. A cross-sectional study of cytomegalovirus retinitis in HIV-1 infected adults in Nigeria. Niger J Clin Pract 2019;22:293-7
|How to cite this URL:|
Adeiza M A, Habib A G. A cross-sectional study of cytomegalovirus retinitis in HIV-1 infected adults in Nigeria. Niger J Clin Pract [serial online] 2019 [cited 2019 May 24];22:293-7. Available from: http://www.njcponline.com/text.asp?2019/22/3/293/253465
| Introduction|| |
Cytomegalovirus (CMV) infection is one of the most important opportunistic infections in HIV-infected patients before the introduction of highly active antiretroviral therapy (HAART). However, recent trends have shown a gradual decrease in CMV retinitis and other CMV end-organ diseases in developing countries with this intervention because of improvement in CMV-specific immune response.,,
CMV end-organ disease in HIV patients results mainly from reactivation of latent infection with patients becoming symptomatic about 3 weeks after reactivation. CMV and other opportunistic infections or malignancies continue to occur in HIV-infected patients who have limited access to medical care, and who develop virologic and immunologic failure to HAART, but the burden of this problem remains unknown in Nigeria.
Predictors of clinical CMV end-organ disease, AIDS, and death include CD4+ T-cell count less than 100 cells/μL, HIV RNA viral load greater than 10,000 copies/μl, and detectable CMV DNA with viral load greater than 200 copies/μl.,
The most common manifestation of CMV infection in HIV infected patients is CMV retinitis. In the pre-HAART era, it occurred in 40% of AIDS patients and accounted for 85% of CMV end-organ disease in HIV/AIDS. It is an important cause of blindness particularly with advanced AIDS (CD4+ count <50 cells/μl)., It has been estimated that between 5% and 25% of HIV-infected patients in the developing world can be expected to develop this disorder at some point during the course of their illness. The reported prevalence in African patients is low, 0 to 8.5% when compared to Europe and the United States. A study by Balo and colleagues in Togo found a cumulative incidence of 21.4% in 200 patients followed up for 20 months. Higher prevalence has been reported in European literature and the low prevalence in Africa may be related to under diagnosis owing to lack of appropriate CMV diagnostic tools  coupled with the absence of ophthalmological services in the routine care of HIV-positive patients in Africa. Mean survival after diagnosis was 22 days in Africa compared to 8 months in Europe., The explanation for this regional variation and short-length of survival in African patients after diagnosis of CMV retinitis is possibly because most African patients present late and die of other AIDS related illnesses before ocular opportunistic infections occur as was observed by Cochereau and colleagues in Burundi.
Characteristic symptoms are floaters, scotoma, photopsia, and blurred vision. In untreated patients with AIDS, the natural history of CMV retinitis is slow but relentlessly progressive necrotizing retinitis with destruction of the whole retina in 3 to 6 months. The zone of retinitis advances at a rate of 750 microns or half a disc diameter every 3 weeks. Blindness from CMV is permanent and may occur well before full destruction of the retina. Retinitis often begins unilaterally, but progression to bilateral disease is common. CMV retinopathy must be distinguished from that because of the other conditions such as toxoplasmosis, herpes simplex virus, herpes zoster virus, tuberculosis, and fungal agents.
The “gold standard” for diagnosis of CMV retinitis is examination of the retina through a dilated pupil by a skilled clinician using an indirect ophthalmoscope. Retinal examination is highly sensitive and specific, and diagnosis is made predominantly on the basis of clinical appearance. CMV retinitis is characterized by dense retinal whitening, which can vary from “fluffy” to “dry and granular in appearance.”, Hemorrhage is frequently present. The retinitis tends to spread centrifugally, often in a brush fire fashion with central clearing where the retina has already been destroyed. The border of active retinitis is irregular with small white satellite lesions, the so called “mozzarella pizza” appearance. The objectives of this study was to determine the prevalence of CMV retinitis and describe the pattern in HIV-1 infected adults in Nigeria.
| Materials and Methods|| |
In a cross-sectional study, 250 newly diagnosed HIV-infected HAART naïve patients were selected by systematic random sampling as they presented to the HIV treatment and care center of our Teaching Hospital. All HIV-infected adults ≥18 years of age who consented to participate were included in the study, whereas HIV-infected adults with refractive errors, systemic hypertension, type 2 diabetes mellitus, and those receiving any form of immunosuppressive therapy were excluded. Patients with suspected tuberculosis, toxoplasmosis, or systemic fungal infections were excluded. Information was obtained from all participants using an interviewer administered questionnaire. All participants had their weight and height taken to calculate body mass index (BMI) and physical examination to determine their clinical state at recruitment. The subjects were screened for symptoms of eye disease such as blurry vision, floaters, and inability to see (blindness). CD4+ T-lymphocyte count was measured, and participants with symptoms of impaired vision and or CD4+ T-lymphocyte count ≤50 cells/μl had indirect ophthalmoscopic examination of the retina in the ophthalmology department to detect CMV related eye lesions; a diagnosis was made when the findings were pathognomonic of CMV retinitis with no other identifiable cause as described by Heiden et al. HIV-RNA viral load was estimated, and complete blood count was performed to determine hemoglobin, total white blood cell count, and percentage of neutrophils, lymphocytes, monocytes and total platelet count. All participants were staged at recruitment using the WHO clinical staging.
Ethical clearance was obtained from the hospital research and ethics committee. There was no significant risk of harm during the study, and patients had the choice of opting out of the study at any stage with no attendant consequences.
Data were analyzed using statistical package for social sciences (SPSS) version 20. Descriptive statistics was presented as means, percentages, and figures, and student's t-test for quantitative variables was used to compare group means between CMV retinitis and non-CMV retinitis HIV-infected participants. The Mann-Whitney U independent non-parametric test was used for quantitative variables, which did not follow normal distribution.
| Results|| |
A total of 250 HIV-positive adults were recruited during the study period. They comprised of 114 (46) males and 136 (54%) females with a male to female ration of 0.85:1. The mean age of study participants was 35.33 ± 6.80 years with a median age of 35 years. The age distribution of the participants is shown [Figure 1]. The predominant age groups were 26–35 years and 36–45 years with 34.4% and 33.6% of participants, respectively. A comparison of mean age, weight, and BMI of CMV retinitis and non-CMV retinitis participants is shown in [Table 1], and there were no statistically significant differences between the groups.
|Table 1: Age, weight, and body mass index (BMI) of CMV retinitis vs. Non-CMV retinitis HIV-positive adults|
Click here to view
History of impaired vision was reported by 21 (8.4%) of participants. Out of the 21 patients, right eye involvement was reported in 7 (33%), left eye involvement in 4 (19%), and both eye in 10 (48%). The predominant symptoms were blurred vision 9 (43%), floaters 9 (43%), and blindness 3 (14%). All affected eyes showed reduced visual acuity, and out of the 21 participants who had fundoscopy, three had characteristic retinal changes-retinal whitening with areas of hemorrhage suggestive of CMV retinitis giving a prevalence of 1.2%. Two (67%) of the CMV retinitis patients were females and 1 (33%) was male. All patients who had CMV retinitis had WHO HIV clinical stage 4 HIV disease stage.
When the hematological parameters and CD4+ T-lymphocyte counts of CMV retinitis and non-CMV retinitis patients were compared using the student's t test, only CD4+ T-lymphocyte count showed a statistically difference between the groups, P < 0.001 [Table 2].
|Table 2: Hematological and CD4+ T-lymphocyte count parameters of CMV retinitis vs. Non-CMV retinitis HIV-positive adults|
Click here to view
A Mann-Whitney U test was conducted for HIV-RNA viral load and CMV IgG antibody titer. For HIV-RNA viral load, the median tendencies for CMV retinitis and non-CMV retinitis HIV-1 infected patients were 210.00 and 124.47. The distribution in the two groups differed significantly (U = 117.00, P = 0.041). There was no statistically significant difference between CMV IgG antibody titer between the two groups (U = 233.00, P = 0.269) [Table 3].
|Table 3: HIV-RNA viral load and CMV IgG antibody titer in CMV retinitis vs. Non-CMV retinitis HIV-positive adults|
Click here to view
All 3 patients with CMV retinitis had advanced HIV/AIDS with WHO clinical stage IV. Death occurred in all 3 patients within 6 months of diagnosis of CMV retinitis.
| Discussion|| |
The distribution of the study participants followed the normal trends in Nigeria and Africa with a female preponderance for obvious health seeking behavior and clustering in the productive age groups of 26 to 45 years. With regard to symptoms of visual impairment, this population presented with blurry vision, floaters, and blindness similar to that described by Heiden. Recognizing these symptoms promptly and referring early for ophthalmological assessment could be a sight saving strategy as retinitis progresses at a rate of half a disc diameter or 750 μm every 3 weeks.
The overall prevalence of CMV retinitis was 1.2% in this study. The prevalence of CMV retinitis from this study is low and similar to 0.2% described by Osahon et al. in Benin City, Nigeria  and 1% by Balo et al. in Togo. Compared to Western literature, this difference is attributable to the fact that patients in sub-Saharan Africa present late coupled with a lack of appropriate diagnostic capability, which tend to be unaffordable even when available., Advance immunosuppression with patients dying of other opportunistic infections at CD4+ count <50 cells/μl before a diagnosis of CMV retinitis can be made may also be contributory.
The most common symptoms seen in participants in this study were blurred vision, floaters, and blindness, whereas the signs seen in the confirmed CMV retinitis patients were retinal whitening with areas of hemorrhage. There appears to be no difference in clinical features when these findings are compared with what has been described in Western literature.
There was a significant association between presence of CMV retinitis and advanced immunosuppression i.e. low CD4+ T-lymphocyte count and high HIV RNA viral load. This is similar to patterns described previously , and is attributable to advanced HIV disease. This is similar to other studies where predictors of clinical CMV end-organ disease, AIDS, and death were CD4+ T-cell count less than 100 cells/μl and HIV RNA viral load greater than 10,000 copies/μl.,
In previous studies, mean survival after diagnosis of CMV retinitis was 22 days in sub-Saharan Africa compared to 8 months in Europe., In this study, it was 2 months. The explanation for this regional variation and short-length of survival in sub-Saharan African patients after diagnosis of CMV retinitis is possibly because most African patients present late and die of other associated AIDS related illnesses as was observed by Cochereau and colleagues in Burundi.
For these myriad of reasons, there is a need for affordable and available CMV diagnostic facilities in developing countries. There is also a need to conduct large scale prospective studies using more sensitive tests such as pp65 antigen capture, DNA PCR, and histology to clearly define the pattern of CMV infection.
| Conclusion|| |
The prevalence of CMV retinitis in this study is 1.2%. CMV retinitis is associated with advanced HIV disease (low CD4+ T-lymphocyte and high HIV-RNA viral load), attendant morbidity (blindness) with high mortality, and absent CMV diagnostic and ophthalmologic services in HIV treatment and care programs in Nigeria.
We recommend a symptom screen for eye disease in tools used for routine care of HIV-infected adults in Nigerian HIV programs, scale-up CMV diagnostic services, and select patients with sight threatening eye disease should be referred to the ophthalmologist to exclude CMV related eye disease.
The study was limited by inability to perform a longitudinal study because of logistics and cost as a longitudinal study design will have given a better picture. This was not possible as most patients had to be commenced on HAART where indicated.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
| References|| |
Cheung TW, Teich SA. Cytomegalovirus infection in patients with HIV infection. Mt Sinai J Med 1999;66:113-24.
Steininger C, Puchhammer-Stöckl E, Popow-Kraupp T. Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART). J ClinVirol 2006;37:1-9.
Springer KL, Weinberg A. Cytomegalovirus infection in the era of HAART: Fewer reactivations and more immunity. J AntimicrobChemother 2004;54:582-6.
Wohl DA, Kendall MA, Andersen J, Crumpacker C, Spector SA, Feinberg J, et al
. Low rate of CMV end-organ disease in HIV-infected patients despite low CD4+cell counts and CMV viraemia: Results of ACTG protocol A5030. HIV Clin Trials 2009;10:143-52.
Tang H, Liu Y, Yen M, Chen Y, Wann S, Lin H, et al
. Opportunistic infections in adults with acquired immunodeficiency syndrome: A comparison of clinical and autopsy findings. J MicrobiolImmunol Infect 2006;39:310-5.
Erice A, Tierney C, Hirsch M, Caliendo AM, Weiberg A, Kendall MA, et al
. CMV and HIV burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (ACTG protocol 360). Clin Infect Dis 2003;37:567-78.
Wohl DA, Zeng D, Stewart P, Glomb N, Alcorn T, Jones S, et al
. Cytomegalovirus viraemia, mortality, and end-organ disease among patients with AIDS receiving potent antiretroviral therapies. J Acquir Immune DeficSyndr 2005;38:538-44.
Ives DV. Cytomegalovirus disease in AIDS. AIDS 1997;11:1791-7.
Chakravarti A, Kashyap B, Matlani M. Cytomegalovirus infection: An Indian perspective. Indian J Med Microbiol 2009;27:3-11.
] [Full text]
Pertel P, Hirschtick R, Phair J, Chmiel J, Poggensee L, Murphy R. Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus. J Acquir Immune DeficSyndr 1992;5:1069-74.
Kestelyn PG, Cunningham ET. HIV/AIDS and blindness. Bull World Health Organ 2001;79:208-13.
Kestelyn P. The epidemiology of CMV retinitis in Africa. OculImmunolInflamm 1999;7:173-7.
Balo KP, Amoussou YP, Bechetoille A, Mihluedo H, Djagnikpo PA, Akpandja SA. Cytomegalovirus retinitis and ocular complications in AIDS patients in Togo. J FrOphthalmol 1999;22:1042-6.
Heiden D, Ford N, Wilson D, Rodriguez WR, Margolis T, Janssens B, et al
. Cytomegalovirus retinitis: The neglected disease of the AIDS pandemic. PLOS MED 2007;4:1845-51.
Burke M, Yust I, Katlama C, Vardinon N, Clumeck N, Pinching AJ, et al
. Cytomegalovirus retinitis in patients with AIDS in Europe. Eur J ClinMicrobiol Infect Dis 1997;16:876-82.
Cochereau I, Mlika-Cabanne N, Godinaud P, Niyongabo T, Poste B, Ngayiragije A, et al
. AIDS related eye disease in Burundi, Africa. Br J Ophthalmol 1999;83:339-42.
De Smelt. Differential diagnosis of retinitis and choroiditis in patients with acquired immunodeficiency syndrome. Am J Med 1992;92:17S-21S.
Hassan-Moosa R, Chinappa T, Jeena L, Visser L, Naidoo K. Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa. S Afr Med J 2017;107:843-6.
Ogoina D, Obiakor OR, Muktar H, Adeiza MA, Babadoko A, Hassan A, et al
. Morbidity and mortality patterns of HIV/AIDS patients in the era of highly active antiretroviral therapy: A 4 year retrospective review from Zaria, Northern Nigeria. AIDS Res Treat 2012;12. doi: 10.1155/2012/940580.
Osahon AI, Onunu AN. Ocular disorders in patients infected with the human immunodeficiency virus at the University of Benin Teaching Hospital, Benin City, Nigeria. Niger J ClinPract 2007;10:283-6.
Laher F, Ashford G, Cescon A, Cullen C, Lazarus E, Puren A, et al
. Held to ransom: CMV treatment in Africa. Southern Afr J HIV Med 2010;11:31-4.
Visser L. Managing CMV retinitis in the developing world. Community Eye Health 2003;16:38-9.
Shi Y, Lu H, He T, Yang Y, Liu L, Zhang R, et al
. Prevalence and clinical management of cytomegalovirus retinitis in AIDS patients in Shanghai, China. BMC Infect Dis 2011;11:326.
Durier N, Ananworanich J, Apornpong T, Ubolyam S, Kerr SJ, Mahanontharit A, et al
. Cytomegalovirus viremia in Thai HIV-infected patients on antiretroviral Therapy: Prevalence and associated mortality. Clin Infect Dis 2011. doi: 10.1093/cid/cit173.
[Table 1], [Table 2], [Table 3]