Incidence of Opportunistic Infections among HIV-Positive Adults on Highly Active Antiretroviral Therapy in a Teaching Hospital,India: Prospective Study

Abstract

Oral manifestations in HIV infections are numerous and some of these are acknowledged as being of great importance in the early diagnosis of the disease. Many HIV-associated oral infections occur early in HIV disease, not infrequently as the presenting sign or symptom. Thus, early detection of the associated oral opportunistic infections should, in many cases, result in earlier diagnosis of HIV infection. Cytology, a simple, painless, and inexpensive method, has become a preferred method and was used in our study for early diagnosis of certain lesions. To determine the effect of highly active antiretroviral therapy on incidence rate of opportunistic infections among HIV-positive adults in a teaching hospital in India, a prospective study was conducted and the required sample size was 40. Study participants were selected randomly from the outpatient department of an HIV clinic who were currently on for antiretroviral therapy (ART). Data on age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4 lymphocytes per milliliter, and viral load were collected. Oral cytologic investigation was carried out and then stained for histopathological examination. A total of 40 individuals were examined and the incidence of opportunistic infections was 66.7% in individuals with CD4 counts less than 200, 55.6% in individuals with CD4 counts of 200 to 499, and 40.0% in individuals with CD4 counts more than 500. The incidence of opportunistic infection was higher in individuals with low CD4 counts in spite of being on ART.

Keywords

candidiasis HIV HAART oral infection

Introduction

HIV infection is characterized by progressive and continuous impairment of the immune system function, with varying rates of progression among patients. Highly active antiretroviral treatments (HAARTs) have been shown to be effective in arresting immune system impairment and prevention of disease progression, yet the incidence of opportunistic infections (OIs) doesn’t seem to cease. Opportunistic infections can occur in about 40% of people living with HIV, with a CD4 count less than 250 cells/mm³.¹ Organisms that cause OIs are frequently present in the body but are generally kept under control by a healthy immune system. HIV gradually weakens a person’s immune system and leads to the development of one or more OIs, which signals the progression of AIDS. These illnesses are generally the eventual cause of death due to HIV infection.²

Among the OIs strongly associated to HIV infection is oral candidiasis. Certain OIs, specifically oral candidiasis and hairy leukoplakia (HL), have been attributed strong diagnostic and prognostic value.^3,4 Moreover, they have recently been proposed as clinical markers of antiretroviral therapy failure.⁵ Cytology, a simple, painless, and inexpensive method, was used to confirm the existence of OI among our participants.

The principal objective of the present study was to assess the prevalence of opportunistic oral infections in patients living with HIV/AIDS receiving HAART.

Participants and Methods

Ethical approval for the study was obtained from institutional ethics committee of Manipal College of Dental Sciences, Mangalore. Informed consent was obtained from all study participants before obtaining oral smears.

The present study included a group of 40 HIV-infected patients seen at an HIV clinic in Kasturba Medical College, Mangalore, India for the diagnosis or follow-up of this infection. All patients had been diagnosed with HIV infection by enzyme-linked immunosorbent assay, and the diagnosis was confirmed by Western blot analysis. Informed consent was received from all patients. The patients seen at this clinic were first evaluated by the physicians who specialized in HIV infection; these physicians determined from the patient’s medical history whether they met the inclusion criteriain the study. The patients selected were referred to the laboratory, where they were examined following an established clinical and microbiological protocol. The clinical protocol consisted of a medical history, social history, and general physical examination. The general examination included careful scrutiny of the oral cavity. Oral smears were collected from normal appearing tongue and buccal mucosa of 40 HIV-infected study participants, and cells were analyzed for the presence of fungal organisms, bacterial colonies, the degree of inflammation, and the type of inflammatory cells seen. Oral cytological analyses of our participants were compared with their CD4 counts. The CD4 lymphocyte counts of each of the 40 cases was noted and categorized as those below 200 cells/mm³, 200 to 499 cells/mm³, and above 500 cells/mm³.

Results

The present study revealed that the prevalence of HIV-associated OIs increased with the decrease in CD4 counts. The prevalence of OIs in patients on HAART was 51.3% (20 cases). The most frequent lesion was erythematous candidiasis with 11 cases, followed by HL with 2 cases. Three patients presented angular cheilitis and 3 were diagnosed with pseudomembranous candidiasis. One case of herpes labialis was registered. This group showed no cases of hyperplastic candidiasis or Kaposi sarcoma. The above result was statistically not significant (Table 1).

Table 1.

Correlation between CD4 Counts and Presence of Infection.

	CD4 Count (cells/mm³)			Total
	<200	200-499	≥500	Total
Infection absent	2 (33.3%)	8 (44.4%)	9 (60%)	19 (48.7%)
Infection present	4 (66.7%)	10 (55.6%)	6 (40%)	20 (51.3%)
Total	6 (100%)	18 (100%)	15 (100%)	39 (100%)

Discussion

In concordance with the principal objective of the study, we identified those participants with opportunistic oral infections in the study group. The overall incidence of OIs was 51.3%. It was higher compared to the results from South Africa (8.52%) and Côte d’Ivoire (36.8%).^6,7 The present study reflects the possibility that opportunistic oral infections associated to HIV infection may manifest as a consequence of immune reconstitution in certain patients living with HIV/AIDS subjected to HAART.

An important finding of our study was that patients living with HIV/AIDS subjected to HAART who present CD4+ lymphocyte counts of >500 cells/mm³ and undetectable viral loads can also suffer from OI. Practically, all studies on oral morbidity in patients living with HIV/AIDS receiving HAART, and in which the prevalence of oral lesions is associated to immune and virological status, report that some patients with CD4+ lymphocyte counts of >500/mL and undetectable viral loads have oral lesions.^8

–14

The clarification of these aspects does not fall within the scope of the present study, and specific investigational protocols should be defined to explore them. Furthermore, it recently has been demonstrated that oral lesion morbidity associated to HIV disease is present in the HIV-positive population under HAART in the present era.¹⁵ At present, we are unable to rule out the possibility that these lesions are the consequence of a qualitative failure of immune cell response, of the incomplete acquisition of mucosal immune response following HAART, or simply examples of de novo infection.

The present study showed the human immunodeficiency syndrome to be a dynamic disorder characterized by an intense interrelationship with therapy; as a result, it is very difficult to establish a prognosis once treatment has been started, though we conclude saying HAART significantly reduced the occurrence of OIs so that initiation of HAART even at higher CD4 count has paramount importance.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Gallant

Moore

Chaisson

. Prophylaxis for opportunistic infections in patients with HIV infection. Ann Intern Med. 1994;120:932–944.

Mariam

Abebe

Mulu

. Opportunistic and other intestinal parasitic infections in AIDS patients, HIV seropositive healthy carriers and HIV seronegative individuals in southwest Ethiopia. East Afr J Public Health. 2008. 5:169–173.

Ramírez-Amador

Ponce-De-León

Sierra-Madero

Soto-Ramírez

Esquivel-Pedraza

Naya-Saavedra

. Synchronous kinetics of CD4+ lymphocytes and viral load before the onset of oral candidosis and hairy leukoplakia in a cohort of Mexican HIV-infected patients. AIDS Res Hum Retroviruses. 2005;21(12):981–990.

Fernández-Feijoo

Diz-Dios

Otero-Cepeda

Limeres-Posse

de la Fuente-Aguado

Ocampo-Hermida

. Predictive value of oral candidiasis as a marker of progression to AIDS. Med Oral Patol Oral Cir Bucal. 2005;10(1):36–40; 32-36.

Gaitán-Cepeda

Martínez-González

Ceballos-Salobreña

. Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART. AIDS Patient Care STDS. 2005;19(2):70–77.

Badri

Ehrlich

Wood

Maartens

. Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations. AIDS. 2001;15:1143–1148.

Anglaret

Messou

Ouassa

. Pattern of bacterial diseases in a cohort of HIV-1 infected adults receiving cotrimoxazole prophylaxis in Abidjan, Côte d’Ivoire. AIDS. 2003;17:575–584.

Aguirre

Echebarria

Ocina

Ribacoba

Montejo

. Reduction of HIV-associated oral lesions after highly active antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88(2):114–115.

Kroidl

Schaeben

Oette

Wettstein

Herfordt

Häussinger

. Prevalence of oral lesions and periodontal diseases in HIV infected patients on antiretroviral therapy. Eur J Med Res. 2005;10(10):448–453.

10.

Cauda

Tacconelli

Tumbarello

. Role of protease inhibitors in preventing recurrent oral candidosis in patients with HIV infection: a prospective case-control study. J Acquir Immune Defic Syndr. 1999;21(1):20–25.

11.

Ceballos-Salobreña

Gaitán-Cepeda

Ceballos-Garcia

Lezama-Del Valle

. Oral lesions in HIV/AIDS patients undergoing highly active antiretroviral treatment including protease inhibitors: a new face of oral AIDS? AIDS Patient Care STDS. 2000;14(12):627–635.

12.

Nicolatou-Galitis

Velegraki

Paikos

. Effect of PI-HAART on the prevalence of oral lesions in HIV-1 infected patients. A Greek study. Oral Dis. 2004;10(3):145–150.

13.

Umadevi

KMR

Ranganathan

Pavithra

. Oral lesions among persons with HIV disease with and without highly active antiretroviral therapy in southern India. J Oral Pathology Med. 2007;36(3):136–141.

14.

Schmidt-Westhausen

Priepke

Bergmann

Reichart

. Decline in the rate of oral opportunistic infections following introduction of highly active antiretroviral therapy. J Oral Pathol Med. 2000;29(7):336–341.

15.

Hamza

Matee

Simon

Kikwilu

Moshi

Mugusi

. Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania. BMC Oral Health. 2006;6:12.