Thyroid Function Disorders in HIV/AIDS Patients in Nepal

Research Article

Annals Thyroid Res. 2016; 2(2): 58-62.

Thyroid Function Disorders in HIV/AIDS Patients in Nepal

Joshi B1,2*, Acharya D³, Shrestha UT¹, Adhikari N¹, Bhandari RK4, Sha SK5, Bhandari R¹ and Dumre SP6*

¹Kantipur College of Medical Sciences, Tribhuvan University, Nepal

²Department of Public Health, Universitas Gadjah Mada, Indonesia

³Biological Sciences, University of Southern Mississippi, USA

4National Public Health Laboratory, Department of Health Services, Nepal

5Little Buddha College of Health Sciences, Purbanchal University, Nepal

6Department of Immunogenetics, Nagasaki University, Japan

*Corresponding author: Joshi B, Department of Public Health, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

Dumre SP, Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Japan

Received: May 13, 2016; Accepted: July 06, 2016; Published: July 08, 2016


Background: Thyroid disorder is one of the common endocrine dysfunctions in Human Immunodeficiency Virus (HIV)-infected individuals under antiretroviral therapy (ART). In Nepal, thyroid disorder is frequently reported in general population, however HIV infected patients under ART are rarely monitored for this problem.

Methods: A cross-sectional study was conducted at National Public Health Laboratory and Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Nepal to investigate the status of thyroid disorder in HIV sero-positive individuals with or without ART. Blood samples were collected and CD4+ T-lymphocyte counts were determined by flow cytometry while thyroid function was assessed by quantitative ELISA.

Results: We investigated a total of 120 HIV/AIDS individuals (including 80 under ART) for thyroid function disorders. In the ART receiving group, 92.3% individuals had hypothyroidism while in ART naïve group only one (7.7%) individual had such disorder. Association between hypothyroidism and ART was statistically significant (p = 0.038). In addition, the rate of hypothyroidism was significantly higher in ART receiving females (p = 0.01). Hypothyroidism status in ART receiving or not receiving individuals and their gender was further fitted in a regression model. After adjusting for gender and ART status in this model, gender remained as an independent predictor of hypothyroidism (Odds Ratio- OR: 5.097, p = 0.031; CI: 1.15-22.47).

Conclusion: High rate of thyroid disorders was observed in ART receiving HIV/AIDS individuals in Nepal. Subclinical hypothyroidism was the most common disorder and females were more vulnerable.

Keywords: HIV/AIDS; Thyroid disorders; Hypothyroidism; Antiretroviral therapy; CD4+ T lymphocyte count; Nepal


AIDS: Acquired Immunodeficiency Syndrome; ART: Anti- Retroviral Therapy; CD: Cluster of Differentiation; ELISA: Enzyme Linked Immunosorbent Assay; fT3: Free Tri-iodothyronine; fT4: Free Thyroxine; HIV: Human Immunodeficiency Virus; MoHP: Ministry of Health and Population; NCASC: National Centre for AIDS and STD Control; NPHL: National Public Health Laboratory; STI: Sexually Transmitted Infection; TSH: Thyroid Stimulating Hormone; WHO: World Health Organization.


Thyroid disorder is one of the common endocrine dysfunctions observed due to alteration in the production of thyroid hormones viz. Thyroxine (T4) and Tri-iodothyronine (T3). Altered production of these hormones often involves dysfunction of thyroid gland, pituitary gland, and hypothalamus [1-3]. Hyperthyroidism (overproduction of T3 and T4) and hypothyroidism (underproduction of T3 and T4) are regarded as the most common clinical forms of thyroid disorders [3].

Human Immunodeficiency Virus (HIV) infected individuals often present with abnormalities in several endocrine functions such as pituitary, thyroid, adrenal, gonads, and pancreas [4-6].

Such endocrine disturbances occur in the course of HIV infection, and underlying pathogenesis generally involves the direct infection of endocrine glands by HIV and opportunistic pathogens, or caused by neoplasm [7,8]. Besides this, adverse effects of prolonged antiretroviral therapy (ART) have also been reported to affect endocrine functions [9,10]. Subclinical hypothyroidism with elevated thyroid stimulating hormone (TSH) is common in individuals with HIV/AIDS [9,11-14]. Although most of the asymptomatic cases with early HIV infection and stable body weight maintain normal thyroid functions, thyroid dysfunctions can appear after the initiation of ART [15,16]. Among thyroid dysfunctions, subclinical hypothyroidism is related to the prolonged use of stavudine [9,14,17]. Although exact mechanism behind the relationship between stavudine use and subclinical hypothyroidism is unclear, stuvadine is believed to affect the production and/or metabolism of thyroid hormones [9]. Therefore, it is important to monitor HIV-infected individuals for thyroid disorders and explore the possible association of thyroid functions with HIV infection, immunodeficiency, and ART status.

Periodic monitoring of thyroid functions in HIV-infected individuals (especially those under ART) has been recommended by various studies across the globe [12,13,18]. Unfortunately, to date, there is no information available on the status of thyroid disorders among HIV-infected population of Nepal, despite the fact that the government has been providing ART services for more than a decade at no cost [19]. In this report, we describe the abnormalities in thyroid functions among Nepalese HIV sero-positive individuals with or without ART.


Study design, population, ethics and enrollment

A cross-sectional study was conducted at National Public Health Laboratory (NPHL), under the Ministry of Health and Population (MoHP)-Nepal between August 2011 and April 2012. HIV seropositive individuals (n = 120) of all age, sex and social classes with different ART status (80 under ART and 40 ART naive) visiting NPHL for regular monitoring of CD4+ T-lymphocyte level were enrolled in the study. HIV/AIDS patients under ART for less than six months and/or patients with proven thyroid disorder prior to HIV confirmation were excluded. Eight individuals who did not wish to participate in the study were also excluded. Approval for this study was obtained from the Research Committees of Tribhuvan University, Kantipur College of Medical Sciences and NPHL. Participants were randomly selected from the designated NPHL register for regular monitoring of CD4+ T-lymphocyte counts and written informed consent was taken from each participant before enrollment in this study. Questionnaires regarding age, sex, duration of HIV, ART status, type and duration of ART were completed followed by blood sample collection. Additionally, relevant clinical information was also obtained from ART center located at Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Nepal.

Laboratory methods and interpretation criteria

All the participants of this study were HIV sero-positive individuals diagnosed by national HIV testing algorithm of National Center for AIDS and STD Control (NCASC). CD4+ T-lymphocyte counts were determined in anticoagulated blood by flow cytometry (Trucount) on a FACS Calibur flow cytometer (BD Biosciences, San Jose, CA, USA). Thyroid function was assessed by measuring free T3, T4 and TSH levels in patient’s serum by quantitative Enzyme- Linked Immunosorbent Assay (ELISA) (Human, Wiesbaden, Germany). As per the manufacturer’s protocol, the normal ranges for TSH, fT3 and fT4 were 0.3-6.2 mIU/l, 1.4 - 4.2 pg/ml and 0.8- 2.0 ng/dl, respectively. Thyroid disorders were categorized as hyperthyroidism (overproduction of T3 and T4) and hypothyroidism (underproduction of T3 and T4). Hypothyroidism or hypothyroid status was further categorized as ‘’overt’’ (high TSH, low fT4), ‘’subclinical’’ (high TSH, normal fT4) and “low fT4” (normal TSH, fT4 = 1.4 pg/ml). Similarly, hyperthyroidism or hyperthyroid status was categorized as ‘’subclinical’’ (TSH = 0.3 mIU/l, normal fT4) and ‘’overt’’ (TSH = 0.3 mIU/l, fT4 > 4.2 pg/ml). This classification is in accordance to the published report [18].

ART Algorithm

According to Nepal ART guidelines 2014 [19], first-line ART consists of two Nucleoside Reverse-Transcriptase Inhibitors (NRTIs) and a Non-Nucleoside Reverse-Transcriptase Inhibitor (NNRTI). The recommended fixed dose combination to initiate ART in Nepal is Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV). But when TDF + 3TC + EFV regimen is contraindicated or not available, the recommended alternatives are - Zidovudine (AZT) + 3TC + EFV, or AZT + 3TC + Nevirapine (NVP), or TDF + 3TC + NVP.

Second line therapy is available at the higher centers with upto- date follow up mechanisms. When Abacavir (ABC) or TDF + 3TC based first-line regimen fails, AZT + 3TC are used as the NRTI backbone in second-line regimens. Similarly, on failure of AZT or Stavudine (d4T) + 3TC based first-line regimen, ABC or TDF + 3TC are used as the NRTI backbone in second-line regimens. Lopinavir (LPV/r) is the preferred boosted Protease Inhibitor (PI).

Data analysis

Data were analyzed by SPSS (Statistical Package for Social Sciences) version 16.0. Normally distributed continuous variables such as age and weight were presented as mean± SD. A significance level > 0.05, and skewness/kurtosis ≈ 0 were regarded as normally distributed population. Chi-square (χ2) test was applied for categorical variables. Bivariate regression model was used to measure the risk predictors of thyroid disorder. A p-value < 0.05 was considered significant for all statistical inferences.


Of the total individuals recruited in this study (n = 120), 66 (55%) were male (male: female = 1.2:1). Mean age of the participants was 34.28 ± 7.3 years, while the mean weight was 53.25 ± 8.7 kg. Two third (66.7%) of the enrolled cases were under ART (Table 1).