Incidence and Predicting Factors of Opportunistic Infections after Antiretroviral Therapy Initiation among Treatment-naïve Patients with HIV Infection: A Retrospective Cohort Study in A Tertiary Care Hospital

Abstract

Objectives

To determine the incidence of opportunistic infections (OIs) and the predictive factors for the development of OIs after antiretroviral therapy (ART) initiation among treatment-naïve patients with HIV infection.

Results

Of 401 HIV-infected patients, 38 (9.5%) HIV-infected patients developed OIs after initiating ART, with an incidence rate of 25.6/1000 person-years. The median time (IQR) from ART initiation to OI occurrence was 26.5 (14-73) days. In multivariate Cox proportional hazard regression, body mass index ≤18.5 kg/m² (adjusted hazard ratio [aHR] 2.28, 95% confidence interval [CI] 1.18-4.42, P = .015), symptoms at presentation (aHR 13.59, 95% CI 3.24-56.9, P < .001), serum glutamate-pyruvate transaminase >55 U/L (aHR 2.09, 95% CI 1.06-4.15, P = .035), and initiation of a dolutegravir-based regimen (aHR 4.39, 95% CI 1.54-12.48, P = .006) were significantly associated with OIs after ART initiation.

Conclusion

OIs after ART initiation are common. Malnutrition, symptomatic presentation, abnormal liver enzymes, and DTG-based regimens are predictors of OI occurrence after ART initiation. Physicians must monitor and appropriately treat OIs after ART initiation.

Keywords

antiretroviral therapy HIV opportunistic infections risk factor Thailand

Introduction

Human immunodeficiency virus (HIV) infection continues to have devastating health effects globally, with over 39 million HIV-related deaths to date and more than 36 million HIV-infected patients currently.¹ Despite substantial advancements in antiretroviral therapy (ART) and worldwide progress toward implementation of treatment-as-prevention programs, approximately 2 million people become newly infected with HIV every year.² Most deaths among HIV-infected patients are attributable to acquired immune deficiency syndrome (AIDS)-defining illnesses. Among non-AIDS-related deaths in HIV-infected patients, most are owing to cancer, followed by stroke, infection, and liver disease.³

In Thailand, approximately 520,000 adults with HIV-infected patients were reported in 2021. Additionally, 6,500 were newly infected with HIV, 450,000 (86%) were currently on ART, and 9,200 died from AIDS.⁴ The main cause of death among HIV-infected patients in Thailand is owing to serious opportunistic infections (OIs).⁵ A recent study showed that 42% of newly diagnosed HIV-infected patients were symptomatic and 32% were diagnosed with AIDS; approximately one-third had OIs at diagnosis of HIV infection, including pulmonary tuberculosis (TB, 73.3%), pneumocystis pneumonia (PCP, 55.8%), extrapulmonary TB (45.3%), and cryptococcosis (16.3%).⁶ In a systemic review and meta-analysis from Switzerland, the most common OIs in ART-naive participants were oral candidiasis (19.1%), unspecified TB (10.0%), herpes zoster (9.4%), pulmonary TB (9.0%), bacterial pneumonia (6.1%), and genital ulcer disease (6.0%).⁷

OIs are the first clinical manifestations that alert clinicians to the occurrence of AIDS. In the context of HIV, OIs are defined as infections that are more frequent or more severe because of HIV-mediated immunosuppression.⁸ When OIs occur, plasma HIV viral load (VL) increases; together, these accelerate HIV progression, increase the risk of HIV transmission, and also increase morbidity and mortality.^9,10 The most important strategy for preventing OIs is ART, as well as medication prophylaxis for some diseases.^11‐13 However, after initiation of ART, immune function improves rapidly and causes systemic or local inflammatory reactions at the site of the preexisting infection or other sites, or unrecognized OIs may develop.¹⁴ Moreover, OIs can develop after virological or immunological failure, despite being on ART.¹⁵ These types of conditions are called “OIs after ART initiation.” Several studies have demonstrated that lower CD4 cell count (≤50 cells/mm³), low baseline bodyweight ≤50 kg, poor adherence to ART, undernutrition, and presentation with advanced World Health Organization HIV clinical stages (III and IV).^16,17 Updated studies regarding this issue are limited. The incidence and clinical characteristics of OIs, as well as risk factors of OIs after ART initiation, might change over time for many reasons, such as early ART initiation, more potent antiretroviral drugs, and a higher proportion of screening OIs before ART initiation. In this study, the authors aimed to determine the incidence of OIs after ART initiation, predictors related to the occurrence of OIs after ART, and mortality owing to OIs after ART.

Materials and Methods

Authors conducted a retrospective cohort study among adults (aged ≥18 years) with a first diagnosis of HIV infection based on positive HIV antibody test results, who were naïve to ART, started ART at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (a 1,200-bed university hospital) from January 2016 to December 2019, and who were followed until 30 June 2022. Individuals were excluded if they had a follow-up visit less than one visit after ART initiation.

Clinical and demographic data, including age when first testing positive for HIV antibody, sex, body mass index (BMI), route of HIV acquisition, comorbidities, clinical presentation, clinical staging, previous OIs before ART initiation, medications for OI prophylaxis, antiretroviral regimen, laboratory investigations, and ART adherence were obtained by reviewing the medical records. Adherence to the latest visit was assessed by the physician and good adherence was defined as more than 90%.¹⁸ Laboratory investigation results, including CD4 cell count, HIV VL, hemoglobin (Hb) level, renal function (creatinine), liver function (serum glutamate-pyruvate transaminase; SGPT), and coinfection with hepatitis B virus (HBsAg), hepatitis C virus (anti-HCV), or syphilis (VDRL and TPHA), were also retrieved and reviewed.

The sample size for a single proportional model¹⁹ was calculated using 95% power to detect an expected prevalence rate of OIs after ART initiation of 44.7%¹⁷ with an expected loss to follow-up of 5% where the significance level (alpha) was 0.05. As a result of this estimation, the sample size was 01. Mean values (with standard deviation [SD]) or median values (with interquartile range [IQR]) and frequency were used to describe patients’ characteristics for continuous and categorical data, respectively. The chi-square test or Fisher's exact test and Student t-test were used to compare categorical variables and continuous variables between the 2 groups, respectively. Baseline characteristics of individuals were compared between HIV-infected patients with and without OIs after ART initiation. The Kaplan–Meier method was used to estimate the cumulative probability of OIs. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine the factors associated with OIs after ART initiation. Variables with a P value <.05 were considered in a multivariate Cox proportional hazard regression model. Variables were entered into a multiple Cox proportional hazard regression model with stepwise forward selection, and variables with P < .05 were retained in the model. The hazard ratio (HR) and its 95% confidence interval (CI) were estimated. A P value <.05 was considered statistically significant. All statistical analyses were performed using Stata Version 17.0 (StataCorp LLC, College Station, TX, USA).

The protocol of this study was reviewed and approved by the Research Ethics Committee of the Faculty of Medicine Ramathibodi Hospital, Mahidol University (No. MURA2021/584). The ethics committee did not require individual consent due to the retrospective study design.

Results

A total of 403 ART-naïve HIV-infected patients were identified from the database. Two HIV-infected patients were excluded due to having follow-up visits less than one visit after ART initiation. Thus, 401 HIV-infected patients were included in the analysis (Figure 1). Among the total, the mean (SD) age was 37.1 (11.9) years, 74.3% were men, and 57.6% had heterosexual risk. The most common comorbidities were hypertension (7%), dyslipidemia (3.7%), and type 2 diabetes mellites (3.5%). Common clinical presentations were asymptomatic (44%), fever (35%), weight loss (30%), pruritic papular eruption (14%), and dyspnea (13.2%). A total of 61.6% were diagnosed with AIDS. Common OIs before ART initiation were pulmonary TB (17%), extrapulmonary TB or disseminated TB (9.5%), candidiasis (13.2%), and PCP (11.5%) (Table 1). As for other coinfections, 10.5% had reactive VDRL, 52% had reactive TPHA, 9.2% had positive HBsAg, and 3.7% had positive anti-HCV. The median (IQR) CD4 cell count at ART initiation was 166 (49-314) cells/µL, and the mean (SD) HIV VL log₁₀ was 4.9 (0.8) copies/mL.

Figure 1.

Study flow chart.

Table 1.

Baseline Characteristics of 401 People Living with HIV Stratified by Status of Having Opportunistic Infections after Antiretroviral Therapy Initiation.

Characteristics	Total(N = 401)	Had OIs(n = 38)	No OIs(n = 363)	P value
Mean (SD) age, years	37.1 (11.9)	37.6 (11.0)	37.0 (12.0)	.536
Male, n (%)	298 (74.3)	31 (81.6)	267 (73.6)	.281
Mean (SD) BMI, kg/m²	22.1 (4.5)	20.1 (4.1)	22.3 (4.5)	.004
HIV risk, n (%)
Heterosexual	231 (57.6)	18 (47.4)	213 (58.7)	.180
Homosexual	169 (42.1)	19 (50)	150 (41.3)	.303
Intravenous drug use	7 (1.7)	1 (2.6)	6 (1.7)	.661
Vertical transmission	2 (0.5)	0	2 (0.6)	1.000
Tattoo	3 (0.7)	0	3 (0.8)	1.000
Unknown	3 (0.7)	1 (2.6)	2 (0.6)	.259
Clinical staging, n (%)
Asymptomatic	113 (28.2)	0	113 (30.7)	<.001
Symptomatic	41 (10.2)	4 (10.5)	37 (10.1)	.949
AIDS	247 (61.6)	34 (89.5)	213 (57.9)	<.001
Underlying disease, n (%)
No underlying disease	344 (85.8)	33 (86.8)	311 (85.7)	.845
Hypertension	28 (7)	2 (5.3)	26 (7.2)	.662
Diabetes mellitus type 2	15 (3.7)	2 (5.3)	13 (3.6)	.603
Dyslipidemia	14 (3.5)	1 (2.6)	13 (3.6)	.762
Hematologic diseases	7 (1.7)	0	7 (1.9)	.388
Heart diseases	5 (1.2)	0	5 (1.4)	1.000
Pulmonary diseases	4 (1)	0	4 (1.1)	1.000
Renal diseases	3 (0.7)	0	3 (0.8)	1.000
Liver diseases	3 (0.7)	0	3 (0.8)	1.000
Rheumatic diseases	3 (0.7)	0	3 (0.8)	1.000
Thyroid diseases	2 (0.5)	1 (2.6)	1 (0.3)	.181
Neurologic diseases	2 (0.5)	0	2 (0.6)	1.000
Clinical presentation, n (%)
Asymptomatic	178 (44.4)	2 (5.3)	176 (48.5)	<.001
Fever	140 (35.0)	26 (68.4)	114 (31.4)	<.001
Weight loss	120 (29.9)	20 (52.6)	100 (27.5)	.001
Pruritic papular eruption	56 (14.0)	6 (15.8)	50 (13.8)	.733
Dyspnea	53 (13.2)	11 (28.9)	42 (11.6)	.003
Candidiasis	49 (12.2)	8 (21.1)	41 (11.3)	.081
Chronic cough	41 (10.2)	9 (23.7)	32 (8.8)	.004
Lymphadenopathy	27 (6.7)	6 (15.8)	21 (5.8)	.019
Chronic diarrhea	10 (2.49)	1 (2.6)	9 (2.5)	.954
Anal abscess	5 (1.2)	0	5 (1.4)	1.000
Herpes infection	3 (0.7)	0	3 (0.8)	1.000
Prior OIs, n (%)
No OIs	242 (60.3)	8 (21.1)	234 (64.5)	<.001
Pulmonary TB	68 (17.0)	15 (39.5)	53 (14.6)	<.001
Extrapulmonary TB or disseminated TB	38 (9.5)	8 (21.1)	30 (8.3)	.010
Candidiasis	53 (13.2)	10 (26.3)	43 (11.8)	.012
Pneumocystis pneumonia	46 (11.5)	11 (28.9)	35 (9.6)	<.001
Herpes virus infection	11 (2.7)	0	11 (3.0)	.277
Cryptococcosis	8 (2.0)	3 (7.9)	5 (1.4)	.006
Cytomegalovirus infection	8 (2.0)	2 (5.3)	6 (1.7)	.13
Mycobacterium avium complex infection	4 (1.0)	0	4 (1.1)	1.000
Toxoplasmosis	3 (0.7)	0	3 (0.8)	1.000
Talaromyces	3 (0.7)	0	3 (0.8)	1.000
Histoplasmosis	1 (0.2)	0	1 (0.3)	1.000
Salmonellosis	4 (1.0)	1 (2.6)	3 (0.8)	.287
Laboratory investigations
Mean (SD) HIV VL log₁₀, copies/mL	4.9 (0.8)	4.97 (1.6)	4.90 (0.63)	.719
Median (IQR) CD4 cell count, cells/µL	166 (49-314)	36 (15-124)	188 (64-335)	<.001
Mean (SD) hemoglobin, g/dL	12.2 (2.2)	10.8 (2.0)	12.4 (2.2)	<.001
Median (IQR) creatinine, g/dL	0.8 (0.69-0.94)	0.74 (0.63-0.90)	0.81 (0.70-0.94)	.218
Median (IQR) SGPT, IU/L	30 (21-46)	32 (20-66)	30 (21-45)	.277
Reactive VDRL, n (%)	42 (10.5)	1 (2.6)	41 (11.3)	.097
Reactive TPHA, n (%)	52 (13.0)	4 (10.5)	48 (13.2)	.638
Positive HBsAg, n (%)	37 (9.2)	3 (7.9)	34 (9.4)	.766
Positive anti-HCV, n (%)	15 (3.7)	1 (2.6)	14 (3.9)	.705
OI prophylaxis, n (%)
No prophylaxis	240 (59.8)	13 (34.2)	227 (62.5)	.001
Co-trimoxazole	142 (35.4)	22 (57.9)	120 (33)	.002
Fluconazole	55 (13.7	12 (31.6)	43 (11.8)	.001
Dapsone	15 (3.7)	2 (5.3)	13 (3.6)	.603
Azithromycin	2 (0.5)	0	2 (0.6)	1.000
Pentamidine	1 (0.2)	1 (2.6)	0	.095
Initial ART, n (%)
Efavirenz-based regimen	348 (86.8)	31 (81.6)	317 (87.3)	.319
Dolutegravir-based regimen	15 (3.7)	4 (10.5)	11 (3)	.021
Median (IQR) time after HIV diagnosis to ART initiation, days	24 (14-40)	24 (21-40)	23 (14-40)	.247
Good ART adherence, n (%)	377 (94)	32 (84.2)	345 (95)	.007

AIDS, acquired immune deficiency syndrome; ART, antiretroviral therapy; BMI, body mass index; CD4, cluster of differentiation 4; CI, confidence interval; HBsAg, surface antigen of hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IQR, interquartile range; OIs, opportunistic infections; SD, standard deviation; SGPT, serum glutamate-pyruvate transaminase; TB, tuberculosis; TPHA, treponema pallidum hemagglutination assay; VDRL, venereal disease research laboratory test; VL, viral load.

The total follow-up time was 526,893 days, with an average of 1,307 days. The median (IQR) time from initiating ART to the occurrence of OIs was 26.5 (14-73) days. Of the total, 38 HIV-infected patients developed OI after ART initiation, with a cumulative incidence of 9.5%. Time at risk was 1,486.06 person-years and the incidence rate was 25.6 per 1,000 person-years. The most common OIs after ART initiation were extrapulmonary TB (34.2%), pulmonary TB (18.4%), cytomegalovirus (CMV) infection (15.8%), PCP (13.2%), and herpes infection (10.5%) (Figure 2). The highest cumulative incidence of OIs was observed during the first year after ART initiation (31 PLWHA, 82%), with an incidence rate of 78 events per 1,000 person-years (Figure 3). More than half (22 HIV-infected patients, 58%) of OIs occurred within the first 3 months after ART initiation.

Figure 2.

Proportion of opportunistic infections after initiation of antiretroviral therapy.

Figure 3.

Cumulative probability of opportunistic infections after initiation of antiretroviral therapy.

HIV-infected patients who developed OIs after ART initiation were more likely to have lower mean BMI (20.1 vs. 22.3 kg/m²), lower median CD4 cell count (36 vs. 188 cells/µL), lower mean hemoglobin levels (10.8 vs. 12.4 mg/dL), and lower ART adherence (84.2% vs. 95%) (P < .05 for all). In contrast, those who developed OI after ART initiation had a higher proportion of AIDS diagnosis (89.5% vs. 57.9%), symptoms at presentation (such as fever, weight loss, and dyspnea) (94.7% vs. 51.5%), prior OIs (78.9% vs. 35.5%), OI prophylaxis (65.8% vs. 37.5%), initiation with a dolutegravir (DTG)-based regimen (10.5% vs 3%), and good adherence (84.2% vs. 95%). The baseline characteristics of HIV-infected patients stratified by status of having OIs after ART initiation are shown in Table 1. The OI-associated mortality was 5.3%.

In univariate Cox proportional hazard regression, BMI ≤18 kg/m² (HR 2.56, 95% CI 1.35-5.00, P = .004), symptomatic at presentation (HR 15.78, 95% CI 3.8-65.56, P < .001), had prior OIs (HR 7.12, 95% CI 3.14-16.19, P < .001), CD4 cell count >200 cells/µL (HR 0.17, 95% CI 0.06-0.44, P < .001), Hb >12 g/dL (HR 0.32, 95% CI 0.16-0.61, P = .001), SGPT >55 U/L (HR 2.60, 95% CI 1.33-5.08, P = .005), received OI prophylaxis (HR 3.05, 95% CI 1.56-5.96, P = .001), DTG-based regimen (HR 4.06, 95% CI 1.43-11.51, P = .008), and good ART adherence (HR 0.32, 95% CI 0.13-0.78, P = .012) were significantly associated with developing OIs after ART initiation (Table 2).

Table 2

Univariate and Multivariate Cox Proportional Hazard Regression of Opportunistic Infections after Antiretroviral Therapy Initiation.

Variables	Univariate		Multivariate
Variables	Hazard ratio(95% CI)	p-value	Hazard ratio(95% CI)	P value
Age >40 years	0.75 (0.38-1.48)	0.405
Female	0.64 (0.28-1.45)	0.286
BMI ≤18.5 kg/m²	2.56 (1.35-5.00)	0.004	2.28 (1.18-4.42)	.015
Had underlying diseases	0.94 (0.37-2.40)	0.885
Symptomatic at presentation	15.78 (3.8-65.56)	<0.001	13.59 (3.24-56.90)	<.001
Had prior OIs	7.12 (3.14-16.19)	<0.001
HIV VL >5 log₁₀ copies/mL	0.82 (0.41-1.65)	0.576
CD4 cell count >200 cells/µL	0.17 (0.06-0.44)	<0.001
Hemoglobin >12 g/dL	0.32 (0.16-0.61)	0.001
Creatinine >1 g/dL	1.15 (0.51-2.61)	0.742
SGPT >55 U/L	2.60 (1.33-5.08)	0.005	2.09 (1.06-4.15)	.035
Positive anti-HCV	0.67 (0.09-4.85)	0.688
Positive HBsAg	0.83 (0.26-2.71)	0.764
Reactive VDRL	0.22 (0.03-1.61)	0.136
Reactive TPHA	0.78 (0.28-2.21)	0.644
OIs prophylaxis	3.05 (1.56-5.96)	0.001
EFV-based regimen	0.64 (0.28-1.44)	0.279
DTG-based regimen	4.06 (1.43-11.51)	0.008	4.39 (1.54-12.48)	.006
Good ART adherence	0.32 (0.13-0.78)	0.012

ART, antiretroviral therapy; BMI, body mass index; CD4, cluster of differentiation of 4; CI, confidence interval; DTG, dolutegravir; EFV, efavirenz; HBsAg, surface antigen of hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; OIs, opportunistic infections; SGPT, serum glutamate-pyruvate transaminase; TPHA, treponema pallidum hemagglutination assay; VDRL, venereal disease research laboratory test; VL, viral load.

In multivariate Cox proportional hazard regression, BMI ≤18.5 kg/m² (adjusted hazard ratio [aHR] 2.28, 95% CI 1.18-4.42, P = .015), symptomatic at presentation (aHR 13.59, 95% CI 3.24-56.9, P < .001), SGPT >55 U/L (aHR 2.09, 95% CI 1.06-4.15, P = .035), and DTG-based regimen (aHR 4.39, 95% CI 1.54-12.48, P = .006) were significantly associated with OIs after ART initiation (Table 2).

Discussion

The results of this study showed that the overall cumulative incidence of OIs after ART initiation was 9.5% and the incidence rate was 25.6 per 1,000 person-years. The most common OIs after initiating ART were extrapulmonary or disseminated TB, pulmonary TB, and CMV infection. BMI ≤18.5 kg/m², being symptomatic at presentation, SGPT >55 U/L, and a DTG-based regimen were significantly associated with OIs after ART initiation. The OI-associated mortality was 5.3%.

The authors found a cumulative incidence similar to other studies conducted in Thailand (8% and 12%).^16,20 In contrast, a study in Ethiopia reported a cumulative incidence of 31.8%, approximately 3 times higher than that in our study.²¹ The incidence rate of OIs after ART initiation in the present study was similar to that of reports from Brazil (26.3 per 1,000 person-years),²² the United States, and Canada (23 per 1,000 person-years).²³ However, the Ethiopian study found an incidence rate of 135 per 1,000 person-years.²¹ The higher cumulative incidence and incidence rate in the Ethiopian study might be explained by a more prolonged duration of follow-up (10 years), a larger sample size, and more HIV-infected patients with poor drug adherence (15%). Poor adherence is likely to lead to virological and immunological failure²⁴ and increases the incidence of OIs after ART initiation. The most common OIs after initiating ART in our study were extrapulmonary or disseminated TB and pulmonary TB. These findings were comparable to those of other studies in Thailand and Ethiopia.^16,21 A possible explanation is that TB is associated with low CD4 cell counts and Thailand is a high-burden country for TB and HIV-associated TB.^25,26 In contrast, the most common OIs after ART initiation in high-income countries such as the United States and Canada are PCP, candidiasis, and Mycobacterium avium complex.²³

The authors determined that predictive factors for developing OIs after ART initiation were low BMI, being symptomatic at presentation, high SGPT levels, and a DTG-based regimen. Malnutrition can cause immune dysfunction and weaken the immune system through atrophy of the thymus, spleen, and lymph nodes, reducing cell-mediated immunity.²⁷ These lead to susceptibility to OIs.²⁸ Previous studies support malnutrition as a risk factor for developing OIs after ART initiation.^16,17 Furthermore, symptoms at HIV diagnosis are a clinical clue for preexisting latent OIs.²⁹ Increased liver enzymes may also indicate the development of an OI because these infections can activate multiple types of immune cells and pathways that cause hepatocyte damage and liver injury.³⁰

There is no available study determining that a DTG-based regimen is a risk factor for OIs after ART initiation among treatment-naïve HIV-infected patients. Most published studies determined DTG-based regimens were associated with immune reconstitution inflammatory syndrome (IRIS), not OIs, after ART initiation. The DTG-based regimen is a potent regimen with more reduced plasma HIV VL compared to those containing protease inhibitors or nonnucleoside reverse transcriptase inhibitors.³¹ It is also associated with faster recovery of CD4 cell counts, which can cause more paradoxical worsening of treated OIs or unmasking IRIS.^14,32 A DTG-based regimen is borderline significantly associated with an increased risk IRIS, with an odds ratio of approximately 2-2.5; however, it is not associated with mortality and hospitalization.³³ However, some studies have shown that a DTG-based regimen is not associated with an increased risk of IRIS; thus, rapid virologic decline may not be the trigger for IRIS.^31,34,35 The differentiation between simple OIs after ART and IRIS is sometimes difficult. In this study, the authors decided to focus on OIs due to the complexity of diagnosing IRIS. The criteria for diagnosing IRIS were not used in this study due to a lack of consensus on the definitions of IRIS.

The strength of this study is that it is the first study in Asia to evaluate OIs after ART initiation in the era of transition from efavirenz (EFV)-based to DTG-based regimens. However, there are some study limitations. First, the nature of a retrospective cohort study can lead to an underestimation of the outcomes and may introduce selection bias. Second, OI diagnoses were based on medical records. Third, most patients had low CD4 cell counts and had initiated EFV-based regimens; therefore, our results may not be able to be generalized to other populations or settings.

In conclusion, the incidence of OIs after ART initiation is not low. We found that the most common OI after ART was TB. Malnutrition, symptomatic presentation, abnormal liver enzymes, and DTG-based regimens are predictors of OI occurrence after ART initiation. It is crucial for physicians to monitor and provide appropriate treatment of OIs after ART initiation to minimize morbidity and mortality.

Footnotes

Acknowledgments

We thank Ms. La-or Nakgul, nurse and study coordinator, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University for retrieving the electronic data of newly diagnosed HIV-infected patients in Ramathibodi Hospital. We also thank Associate Professor Sasivimol Rattanasiri, Mr. Nattawut Unwanatham, and Assistant Professor Kunlawat Thadanipon, a statistician from the Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, for the statistical analysis. We thank Analisa Avila, MPH, ELS, of Edanz () for editing a draft of this manuscript.

Availability of Data and Materials

The datasets generated and analyzed during the current study are not publicly available owing to institutional policy but are available from the corresponding author upon reasonable request.

Authors’ Contributions

PW and SK: research idea and study design; PW: data acquisition; PW and SK: data analysis/interpretation; PW and SK: statistical analysis.

Declaration of Conflicting Interests

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

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Sasisopin Kiertiburanakul

References

UNIAIDS. Global HIV & AIDS Statistics. 2021 [cited 2023 Aug 20]. Available from: https://www.unaids.org/en/resources/fact-sheet.

Pandey

Galvani

. The global burden of HIV and prospects for control. Lancet HIV. 2019;6(12):e809‐e811.

Croxford

Kitching

Desai

, et al. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: An analysis of a national observational cohort. Lancet Public Health. 2017;2(1):e35‐e46.

UNAIDS. Thailand country factsheets. 2021 [cited 2023 Aug 20]. Available from: https://www.unaids.org/en/regionscountries/countries/thailand.

Manosuthi

Charoenpong

Santiwarangkana

. A retrospective study of survival and risk factors for mortality among people living with HIV who received antiretroviral treatment in a resource-limited setting. AIDS Res Ther. 2021;18(1):71.

Eamsakulrat

Kiertiburanakul

. The impact of timing of antiretroviral therapy initiation on retention in care, viral load suppression and mortality in people living with HIV: A study in a university hospital in Thailand. J Int Assoc Provid AIDS Care. 2022;21:23259582221082607. doi:https://doi.org/10.1177/23259582221082607

Low

Gavriilidis

Larke

, et al. Incidence of opportunistic infections and the impact of antiretroviral therapy among HIV-infected adults in low- and middle-income countries: A systematic review and meta-analysis. Clin Infect Dis. 2016;62(12):1595‐1603.

National Institutes of Health, Centers for Disease Control and Prevention, and the HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. 2022 [cited 2023 Aug 20]. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-oi/guidelines-adult-adolescent-oi.pdf.

Lawn

Butera

Folks

. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev. 2001;14(4):753‐777.

10.

Bentwich

. Concurrent infections that rise the HIV viral load. J HIV Ther. 2003;8(3):72‐75.

11.

Ledergerber

Egger

Erard

, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: The Swiss HIV cohort study. JAMA. 1999;282(23):2220‐2226.

12.

Brooks

Kaplan

Holmes

Benson

Pau

Masur

. HIV-associated opportunistic infections—going, going, but not gone: The continued need for prevention and treatment guidelines. Clin Infect Dis. 2009;48(5):609‐611.

13.

Palella

Delaney

Moorman

, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338(13):853‐860.

14.

Lawn

Bekker

Miller

. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis. 2005;5(6):361‐373.

15.

Mulisa

Tolossa

Bayisa

Abera

Wakuma

. First-line virologic-based ART treatment failure and associated factors among adult HIV positives in southwest Shoa, central Ethiopia. J Int Assoc Provid AIDS Care. 2022;21:23259582221111080. doi:https://doi.org/10.1177/23259582221111080

16.

Manosuthi

Chaovavanich

Tansuphaswadikul

, et al. Incidence and risk factors of major opportunistic infections after initiation of antiretroviral therapy among advanced HIV-infected patients in a resource-limited setting. J Infect. 2007;55(5):464‐469.

17.

Woldegeorgis

Zekarias

Adem

Obsa

Kerbo

. Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis. Front Med (Lausanne). 2023;10:1087086.

18.

Ortego

Huedo-Medina

Llorca

, et al. Adherence to highly active antiretroviral therapy (HAART): A meta-analysis. AIDS Behav. 2011;15(7):1381‐1396.

19.

Naing

Nordin

Rahman

Naing

TY . Sample size calculation for prevalence studies using Scalex and ScalaR calculators. BMC Med Res Methodol. 2022;22(1):209.

20.

Boonnoi

Tingpej

Homkham

. Incidence and risk factors of opportunistic infections in HIV-infected adults on antiretroviral therapy. Sci Tech Asia. 2022;27(4):58‐68.

21.

Dagnaw Tegegne

Cherie

Tadesse

Tilahun

Kassaw

Biset

. Incidence and predictors of opportunistic infections among adult HIV infected patients on anti-retroviral therapy at Dessie Comprehensive Specialized Hospital, Ethiopia: A retrospective follow-up study. HIV AIDS (Auckl). 2022;14:195‐206.

22.

Candiani

Pinto

Cardoso

, et al. Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais state, Brazil. Cad Saude Publica. 2007;23:S414‐S423.

23.

Buchacz

Lau

Jing

, et al. Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000-2010. J Infect Dis. 2016;214(6):862‐872.

24.

Bezabhe

Chalmers

Bereznicki

Peterson

. Adherence to antiretroviral therapy and virologic failure: A meta-analysis. Medicine (Baltimore). 2016;95(15):e3361.

25.

Yang

Kong

. The bacterial and host factors associated with extrapulmonary dissemination of Mycobacterium tuberculosis. Front Biol (Beijing). 2015;10(3):252‐261.

26.

World Health Organization. Significant milestone of ending TB: WHO announces Thailand is no longer listed in high-burden countries for drug resistant TB. 2021 [cited 2023 Aug 20]. Available from: https://www.who.int/thailand/news/detail/02-07-2021-significant-milestone-of-ending-tb-who-announces-thailand-is-no-longer-listed-in-high-burden-countries-for-drug-resistant-tb.

27.

Bourke

Berkley

Prendergast

. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 2016;37(6):386‐398.

28.

Katona

Katona-Apte

. The interaction between nutrition and infection. Clin Infect Dis. 2008;46(10):1582‐1588.

29.

Murdoch

Venter

WDF

Van Rie

Feldman

. Immune reconstitution inflammatory syndrome (IRIS): Review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4:9.

30.

Hastings

Green

Gao

Ganey

Roth

Burleson

. Beyond metabolism: Role of the immune system in hepatic toxicity. Int J Toxicol. 2020;39(2):151‐164.

31.

Rossetti

Baldin

Sterrantino

, et al. Efficacy and safety of dolutegravir-based regimens in advanced HIV-infected naïve patients: Results from a multicenter cohort study. Antiviral Res. 2019;169:104552.

32.

Müller

Wandel

Colebunders

Attia

Furrer

Egger

. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: A systematic review and meta-analysis. Lancet Infect Dis. 2010;10(4):251‐261.

33.

Wijting

IEA

Wit

Rokx

, et al. Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy. EClinicalMedicine. 2019;17:100210.

34.

Dooley

Kaplan

Mwelase

, et al. Dolutegravir-based antiretroviral therapy for patients coinfected with tuberculosis and human immunodeficiency virus: A multicenter, noncomparative, open-label, randomized trial. Clin Infect Dis. 2019;70(4):549‐556.

35.

Zhao

Hohlfeld

Namale

Meintjes

Maartens

Engel

. Risk of immune reconstitution inflammatory syndrome with integrase inhibitors versus other classes of antiretrovirals: A systematic review and meta-analysis of randomized trials. J Acquir Immune Defic Syndr. 2022;90(2):232‐239.