CD4 lymphocyte response following anti-retroviral therapy in HIV/AIDS patients - A study in Osmania General Hospital

The present study aimed at serial three year assessment of CD4 cell response after initiation of anti-retroviral therapy (ART) in patients with HIV/AIDS attending to Osmania General Hospital. It was a retrospective hospital based observational study. Data was collected over a period of 3 years from 2005 to 2007 in the ART Centre, Department of Medicine, Osmania General Hospital. We included 110 HIV/AIDS who were on ART. Serial monitoring of CD4 count was done and assessed. All patients were on ART as per National Aids Control Organisation (NACO) guidelines. Investigations included complete blood picture, serum creatinine, blood urea, serum electrolytes, liver function tests, sputum for acid fast bacilli, chest radiography, CD4 cell count and if required fine needle aspiration and biopsy, magnetic resonance imag-ing, computerized tomography, colonoscopy were also performed. The result of the present study shows increase in mean CD4 count by 128.78 cells/mm 3 after 6 months of initiation of ART, 24.77 cells/mm 3 after 1 year, 67.53 cells/mm 3 after 2 years and 5.59 cells/mm 3 after 3 years from the base line CD4 cell count. It certainly reveals the improvement in the CD4 count after ART initiation. Improvement in CD4 count was almost equal in both male and female and in all age groups. Mean CD4 cell count improved by 240.31 cells/mm 3 in females and 220.54 cells/mm 3 in males from the baseline after 3 years of treatment with ART. The present study clearly shows definite improvement in CD4 cell count after ART of more than 100% irrespective of age and sex. Regular intake of drugs will improve immunologic response. Therefore, strict adherence to ART and regular counselling sessions at ART centres should be stressed upon.

The present study aimed at serial three year assessment of CD4 cell response after initiation of anti-retroviral therapy (ART) in patients with HIV/AIDS attending to Osmania General Hospital. It was a retrospective hospital based observational study. Data was collected over a period of 3 years from 2005 to 2007 in the ART Centre, Department of Medicine, Osmania General Hospital. We included 110 HIV/AIDS who were on ART. Serial monitoring of CD4 count was done and assessed. All patients were on ART as per National Aids Control Organisation (NACO) guidelines. Investigations included complete blood picture, serum creatinine, blood urea, serum electrolytes, liver function tests, sputum for acid fast bacilli, chest radiography, CD4 cell count and if required fine needle aspiration and biopsy, magnetic resonance imaging, computerized tomography, colonoscopy were also performed. The result of the present study shows increase in mean CD4 count by 128.78 cells/mm 3 after 6 months of initiation of ART, 24.77 cells/mm 3 after 1 year, 67.53 cells/mm 3 after 2 years and 5.59 cells/mm 3 after 3 years from the base line CD4 cell count. It certainly reveals the improvement in the CD4 count after ART initiation. Improvement in CD4 count was almost equal in both male and female and in all age groups. Mean CD4 cell count improved by 240.31 cells/mm 3 in females and 220.54 cells/mm 3 in males from the baseline after 3 years of treatment with ART. The present study clearly shows definite improvement in CD4 cell count after ART of more than 100% irrespective of age and sex. Regular intake of drugs will improve immunologic response. Therefore, strict adherence to ART and regular counselling sessions at ART centres should be stressed upon.
he development of effective anti-retroviral therapy (ART) for human immunodeficiency virus (HIV) infection is one of the most notable achievements in modern medicine. The first cases of acquired immunodeficiency syndrome (AIDS) were reported from Los Angeles in 1981. In the early to mid -1980s, without any available antiretroviral treatment, the life expectancy of an T J Med Allied Sci 2016;6 (2) individual diagnosed with AIDS was only approximately 6 to 12 months. The first anti-retroviral drug, Zidovudine (Azidothymidine, AZT) was approved by the US Food and Drug administration (FDA) in 1987 on the basis of a short term survival benefit. Triple drug therapy was first introduced in the mid-1990s and resulted in a two thirds decrease in HIV related deaths within 2 years in developed countries. Presently there are a total of 28 antiretroviral drugs that are approved by the FDA and three drug combination regimens are the standard of care. The benefits of ART were extended to developing countries, and an estimated over 14 million people currently are taking ART worldwide. The life expectancy of an HIV-infected individual appropriately treated with ART is now estimated to be nearly that of the general population, both in developed and developing countries 1-3. As of the end of 2010, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that 34 million (31.6-35.2 million) 4 people were living with human immunodeficiency virus (HIV)infection, globally. HIV infection can be diagnosed with a rapid point-of-care blood test, but only half of all persons living with HIV worldwide are aware of their infection [5][6][7] . During 2010, an estimated 2.7 million (2.4-2.9 million) new infections occurred worldwide, including an estimated 3,90,000 among children, and approximately 1.8 million (1.6-1.9 million) people died of AIDS-related causes 6,7 . Furthermore, there has been increasing awareness that early initiation of ART may significantly decrease HIV transmission and have a societal prevention benefit additional to individual clinical benefit 2,[8][9][10][11] . With continuing advances in HIV drug development, the goal of antiretroviral therapy for all patients is to achieve an undetectable viral load in the blood using an ultrasensitive assay. Effective antiretroviral therapy should also result in restoration of at least partial cell-mediated immunity with successful treatment resulting in a rise of CD4 lymphocyte cells (CD4 cells) of 50 to 100 cells/mm 3 at the end of 1 year 12 .

Materials and methods
It was a retrospective hospital based observational study. We included 110 HIV/AIDS who were on ART. Data was collected over a period of 3 years from 2005 to 2007 in the ART centre, Upgraded Department of Medicine, Osmania General Hospital. Data collected was assessed for mean CD4 cell count, trends, age and sex wise distribution. All patients were on ART as per NACO guide lines.
Investigations: Complete blood picture, serum creatinine, blood urea, serum electrolytes, liver function tests, sputum for acid fast bacilli, chest radiography, CD4 cell count were done in all patients. If required fine needle aspiration and biopsy, magnetic resonance imaging, computerized tomography and colonoscopy were also performed.

Results
Out of 110 patients, 64 were male and 46 were female and mostly in the age groups of 21-40 years. Out of 64 male patients, only 1 patient was less than 20 years of age, 53 patients were in the age group of 21-40 years and 10 were in the age group greater than 40 yrs (Table1 and Fig 1).   Fig 2).   In HIV patients, CD4 + cell count is a major indicator of immunodeficiency, a pointer for initiating ART and for monitoring treatment response.
Among those with human immunodeficiency virus (HIV) infection, the CD4 + T-lymphocyte count is the major indicator of immunodeficiency, a main factor in deciding whether to initiate highly active antiretroviral therapy (HAART), and an important parameter in monitoring treatment response 15,16 .
Studies of the kinetics of CD4 + count response post-HAART indicate that the CD4 + count increases rapidly during the first 3-6 months, in part due to release of memory T-cells from lymphoid tissue, and then increases slowly during the next 3-4 years, reflecting reconstitution of the immune system 17 . The rate of CD4 + recovery depends on various factors like baseline CD4 + count at HAART initiation, age of the patient, maintenance of virologic suppression.
ART initiation guidelines used in developing countries have been based on both clinical and laboratory parameters 18,19 . In the face of high AIDS mortality, initial prioritization was to rapidly expand antiretroviral access to the largest number of patients with advanced clinical disease. Late presentation is costly in terms of morbidity and mortality 10 and utilization of healthcare resources and also limits the potential for restoration of immune function 2 . Treatment of patients with earlier disease is less demanding, results in better outcomes utilizing less health resources and also decreases the proportion of the population progressing to AIDS. In 2010, the WHO changed the recommended CD4 T-cell initiation threshold from 200 to 350 cells/μL in addition to clinical stages 3 and 4. However, implementation of CD4 count criteria only has utility when there is wider access to CD4 counts integrated with voluntary counselling and at all interfaces with the healthcare system 8 .The trend for earlier ART initiation is further supported by recognition of lower HIV transmission from HIV-infected partners of discordant sexual relationships with CD4 cell counts above current treatment thresholds who are receiving effective ART 9 . Furthermore, modelling exercises have proposed that universal early initiation of ART has the potential to prevent HIV transmission at a population level. . In most patients, the CD4 cell count rises with the initiation of ART and immune recovery. However, this may be blunted if the baseline CD4 count is low. In general, the lower the baseline CD4 count is at the start of ART, the longer it will take for the count to increase with time. In some patients, clinical improvement may never correlate with CD4 + count i.e. counts never reach 200cells/mm 3 .
In those who have achieved a substantial peak response, a subsequent progressive decline in the CD4 count in the absence of inter current illness indicates an immunological failure (determined by the trend of regular six-monthly CD4 counts).
Ensuring good adherence to the treatment is imperative for the success of the national programme as well as for the prevention of drug resistance. To achieve this, counselling must start from the first contact visit by the clinical team and should include preparing the patient for treatment and providing psychosocial support through an identified guardian and through support networks. All patients should undergo at least two counselling sessions before the initiation of ART 20 .

Conclusion
Present study clearly shows definite improvement in CD4 cell count after ART is more than 100% irrespective of age and sex. Therefore strict adherence to ART /regular counselling sessions at ART centres should be stressed.