{'fraction_non_alphanumeric': 0.021450747953711543, 'fraction_numerical': 0.03227020415843447, 'mean_word_length': 4.58591697320021, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Profile of highly active antiretroviral therapy failure human immunodeficiency virus patients at a tertiary health care centre of India: a success story of NACP

Background: Although HAART has successfully controlled the progression of HIV and helped to prevent the disease significantly, new challenges are heading up and ART failure despite of good adherence is becoming a major hurdle in the way of HIV control. Considering these facts present study was planned with an objective to study clinical and immunological profile of antiretroviral therapy failure HIV patients. Methods: This observational study was conducted at ART plus centre of one of the tertiary health care centre of India from February 2018 to September 2019. Patients satisfying inclusion and exclusion criteria were interviewed by using semi-structured questionnaire and were examined and investigated for any opportunistic infections and their CD4 counts were studied. Results: Among total 4098 patients alive on ART at present study centre 90.6% were responding well to the 1 line of ART, while 8.7% had failed to 1st line of ART but responding well to the 2 line whereas 0.7% had failed to 2 line and were initiated on 3 line of ART. Failure of ART was the cause for change in regimen among 84.9% of patients. Median of rise in CD4 count at 6 months from switch to 2 line was 137 cells/mm. Conclusions: Antiretroviral therapy has significantly improved outcome of the disease. Failure of ART is the major cause for change in ART regimen. Majority of patients in failure had WHO clinical stage 1 and 2.


INTRODUCTION
Human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) is pandemic, with infected patients has been reported from nearly every country in the world. Unlike other epidemics, AIDS falls most heavily on young adults in their prime, posing a grave challenge in the areas of health, social and economic development. 1 National adult (15-49 years) HIV prevalence in India was estimated at 0.22% in 2017. Estimated adult HIV prevalence of Maharashtra was 0.33% which is higher than that of national prevalence. 2 ART centre of present tertiary care centre was established in 2006 and was upgraded as ART plus centre in 2011. This ART plus centre has been connected with network of ART centres as well as Linked ART centres (LACs). Till the end of this study almost 15874 patients were registered under pre ART at this centre and 10953 patients were registered under ART out of which 4098 patients were alive on ART. Highly active antiretroviral therapy (HAART) has become a major turning point in response to the HIV/AIDS epidemic. HAART treatments effect is clearly evident, as increased survival, decreased HIV associated mortality and vastly improved quality of life. An infectious disease which was previously used to be considered to have almost universally fatal outcome has been transformed into a manageable chronic infectious disease. 3 In India demographic, geographic, economical and resource related problems has posed great difficulty on providing HAART but national programme of India has achieved great success overcoming these hurdles and has globally acclaimed as a success story. The National AIDS Control Programme (NACP) is being implemented as a comprehensive programme for prevention and control of HIV/AIDS in India. 4 Although HAART has successfully controlled the progression of HIV, new challenges are heading up and ART failure despite good adherence is becoming a major hurdle in the way of HIV care. The present study was conducted with the objectives to study sociodemographic, clinical and immunological profile of antiretroviral therapy failure HIV patients.

METHODS
The present study was a hospital based observational descriptive study and was carried out in the Department of General Medicine of tertiary health care centre. Approval from the Institutional Ethical Committee was taken before start of the study. The present study was carried out from February 2018 to September 2019.

Inclusion criteria
We included those HIV infected patient older than fifteen years and were failing on ART (as defined by WHO guidelines), registered under ART plus centre and also admitted to medicine wards of present study teaching institute.

Exclusion criteria
Pregnant females, patients lost for follow up, Patients transferred out under linked ART centre, newly diagnosed along with patients on ART for less than 6 months and those who were not willing to participate were excluded from the study. Out of total 4098 patients 3714 (90.6%), 357 (8.7%) and 27 (0.7%) patients were on 1 st , 2 nd and 3 rd line of ART respectively. Among all these, 303 and 27 of 1 st and 2 nd line failures respectively were fulfilling all the inclusive and exclusive criteria's. Thus we studied total 330 study subjects during the study period.

RESULTS
At the present study ART centre 10953 patients were initiated on ART since 2006 out of which 4098 patients were alive taking ART from the present study ART centre till the end of the study period, 1968 patients died on ART, 442 patients were lost to follow up, 383 patients opted out voluntarily and 4062 patients were transferred out to other ART and linked ART centres. Among 4098 patients on ART maximum no. of patients (n=3714; 90.61%) were responding well to the 1 st line of ART, whereas 357 patients were on 2 nd line of ART among which 303 were shifted to 2 nd line of ART due to failure of ART and only 27 patients were on the 3 rd line of ART.
In the present study maximum no. of patients belonged to the age group 31 years to 50 years. Present study population was predominantly composed of male patients, consisting of 63%, 74% of total patients of 1 st and 2 nd line failure respectively. From both 1 st line and 2 nd line failures (172(57%) and 20 (74%) patients respectively) maximum proportion of patients were from the rural areas. Maximum numbers of patients were married. Proportion of unmarried patients increased as line of failure progressed from 1st line failure to 2 nd line failure as only 3% of 1 st line failures were unmarried whereas proportion of unmarried patients increased to 11% of patients from 2 nd line failure.
Almost 52 (17%) of 1st line ART failure patients were illiterate and maximum proportion of patients i.e. 44% and 41% from 1 st and 2 nd line ART failure respectively had acquired education upto secondary school. Interesting observation was maximum number of patients were from upper lower class as per Kuppuswamy socieoeconomical classification. Among study population majority of patients had BMI within normal range i.e. 18.5-24.9 kg/m 2 . Mean BMI of 1 st line and 2 nd line failure patients was normal. Also mean BMI of females was lower than that of males.
Heterosexual route was the predominant route of transmission among all lines of failure patients. 89% and 85% of 1st line and 2n d line failure patients respectively had acquired HIV by heterosexual route. Proportion of patients with mother to child transmission of HIV seen to be increasing as line of failure advances from 1 st line to 2 nd line failure as only 2% of 1 st line failure patients had acquired HIV vertically which increased to 11% of 2 nd line failures (Table 1).  Total 98 (32%), 16 (59%) patients from 1 st , 2 nd line ART failures respectively were started on ART after 6 months of delay from the detection of HIV. Median duration between detection of HIV and initiation of ART was 1 month among 1 st line ART failure patients (Figure 2). till the end of study period) was 265.5 cells/mm 3 that after 12 months of shift was 350.5 cells/mm 3 (n=206, as only 206 patients had completed 12 months from the switch to 2 nd line of ART). Rise in CD4 counts from the count at the time of failure was seen in 217 out of 242 patients at 6 months and median of rise in CD4 count at 6 months from switch to 2 nd line was 137 cells/mm 3 whereas persistent fall in CD4 count was seen in 25 patients and median of fall in CD4 count was 14 cells/mm 3 . Rise in CD4 counts from the count at the time of failure was seen in 192 out of 206 patients at 12 months and median of rise in CD4 count at 12 months from switch to 2 nd line was 218 cells/mm 3 whereas persistent fall in CD4 count was seen in 14 patients and median of fall in CD4 count was 78 cells/mm 3 (Table 2).   Extra pulmonary tuberculosis was found to be the most common opportunistic infection at the time of failure to ART and tuberculous pleural effusion was observed to be the most common form of extra pulmonary tuberculosis.
In present study population extra pulmonary tuberculosis occurred at median CD4 count of 96 cells/mm 3 (Figure 3).

DISCUSSION
In our observational study we studied demographic, clinical and immunological profile of HIV patients failing on HAART.
Present study population was predominantly composed of male patients (63%), and most of studies done in India and all over the globe showed male predominance in HIV infection. [5][6][7][8][9] We observed that maximum proportion of patients were from middle age group and from earning population (70% and 74% of 1 st and 2 nd line failure respectively  12,15 In contrast to these observations 45% of present study population had WHO stage 1 and only 16% had WHO stage 4 at the time of failure.
As during initial period of the study, viral load testing was not available at present study centre hence only suspected failure patients were advised viral load testing which is the major limitation in developing countries in the care of HIV patients.

CONCLUSION
Results of present study throw a light on the fact that antiretroviral therapy has significantly improved outcome of the disease caused by HIV infection in terms of improvement in clinical and immunological status even after failure of initial lines of ART. We also observed that Failure of ART is the major cause for change in ART regimen among patients with good adherence to treatment. Majority of patients in Immunological and virologic failure had WHO clinical stage 1 and 2 at the time of failure which is a sign of early detection of failing patients. We also observed that delay in initiating ART is more associated with failure of ART hence it is recommended that to start HAART as early as possible after diagnosis of HIV infection. Extra pulmonary tuberculosis was found to be most common opportunistic infection at the time of failure. ART centres and linked ART centres has contributed to reduce the prevalence of HIV and improved care of HIV infected patients in India by different ways telling the success story of NACP.