Baseline characteristics and immunological response to antiretroviral therapy in HIV-2 patients

 

 

Abstract              Background: HIV-2 differs from HIV-1 as it is associated with lower viral load levels and slower rates of CD4 decline and clinical progression compared with HIV-1. Aim: To study baseline characteristics and immunological response to antiretroviral therapy in HIV-2 patients. Material and Methods: This cross-sectional study included HIV-2 patients who visited ART centre in tertiary care hospital through SACEP and / or HIV-2 patients admitted in the medical wards and who were documented HIV-2 reactive with western blot confirmation. Every 6 monthly CD4 counts of all patients were noted. Immunological response to ART was evaluated during the course of study period. Results: Median baseline CD4 count of study population was 211 (123.7-303.2 cells /μl). The immunological response to ART after 6 months and after 12 months of starting ART was analysed in 164 patients. An increase in median CD4 count from baseline at 6 months (+102.5 cells /μl) and at 12 months (+135 cells /μl) was observed. Conclusion: An increase in median CD4 count at 6 months and 12 months from the baseline median CD4 count was observed. The response to ART and the pattern of resistance to ART is unique; and further studies should be carried out for the same.

Key Words: HIV-2, CD4 count, ART treatment, Immunological response

 

INTRODUCTION

HIV-1 and HIV-2 are closely related retroviruses of the same genus (Lentiviridae) and share the same modes of transmission. However, HIV-2 differs from HIV-1 as it is associated with lower viral load levels and slower rates of CD4 decline and clinical progression compared with HIV-1;^1,2 86% to 95% of people infected with HIV-2 are long-term nonprogressors.^3,4 Recent data show that survival of persons with undetectable HIV-2 viral load is similar to that of the general population.⁴ However, HIV-2 can cause immune-suppression, as well as AIDS characterized by the same signs, symptoms, and opportunistic infections that are seen in HIV-1. HIV-2-associated AIDS may often be associated with lower viral load levels than HIV-1 (>10,000 copies/mL in HIV-2 versus sometimes millions of copies/mL in HIV-1)^.4

The prolonged course of human immunodeficiency virus (HIV) infection is marked by a decrease in the number of circulating CD4+T helper cells and persistent viral replication, resulting in immunologic decline and death from opportunistic infections and neoplasm.^5,6 Our institution has an ART centre which is one of the largest in the country and has a centre of excellence which caters to special situations like HIV-2 patients, first line ART failure and patients with adverse reaction to ART. The present study was conducted to study baseline characteristics and immunological response to antiretroviral therapy in HIV-2 patients.

 

MATERIAL AND METHODS

Study design

This cross-sectional study included HIV-2 patients who visited ART centre in tertiary care hospital through SACEP and / or HIV-2 patients admitted in the medical wards and who were documented HIV-2 reactive with western blot confirmation. Western blot confirmation was obtained by sending samples to NARI, Pune. The study protocol was reviewed and approved by the Institute Ethics Committee.

Patient definition

Any HIV-2 reactive with western blot confirmation patient registered at ART centre or admitted in medical wards and who fulfilled the inclusion criteria.

Patients selections

All the HIV-2 patients who visited ART centre in tertiary care hospital through and / or HIV-2 patients admitted in the medical wards were included in the study provided they fulfilled the following criteria.

Inclusion criteria

• All HIV-2 reactive patients with western blot confirmation enrolled at ART centre.
• HIV-1 and HIV-2 co-infected patients.
• All above patients who gave written informed consent were included in study.

Exclusion criteria

• All HIV-1 reactive patients who were non-reactive for HIV-2 infection.
• Patients who did not give written informed consent.

Data collection

Sociodemographic data, WHO clinical staging of study population at the time of initial visit, 6 monthly CD4 counts, ART data were obtained from patient admitted in medicine wards, from ART centre, from white cards available at ART centre, from green book (ART registration book), from SACEP records with NACO permission and from previous case paper records if any available.

Clinical evaluation

Detailed history and clinical examination were done on every ART visit days starting from the day of inclusion into study. All the patients were evaluated at the time of each visit at ART centre for associated symptoms, opportunistic infections. Every 6 monthly CD4 counts of all patients were noted and occurrence of opportunistic infections with respect to CD4 count was evaluated. Immunological response to ART was evaluated during the course of study period. For the patients who were admitted in medical wards, detailed history and clinical examination were done and details of opportunistic infections, clinical profile and 6 monthly CD4 were taken.

Statistical analysis

Stata SE 13.1 was used to analyse data. Mean, Standard deviation, Standard error, 95% Confidence intervals were calculated. If the variable is not normally distributed, Median and Interquartile range were used. Normality was assessed by the Shapiro-Wilk procedure. Mann Whitney U test was used to test variables that were not normally distributed with 2 groups. Spearman`s correlation coefficient (rho) was used to correlate 2 quantitative variables. A p value (significance) of < 0.05 (Sig.) was deemed statistically significant, p <0.01 as highly significant (HS) and p < 0.0001 as very highly significant (VHS).

 

RESULTS

In our study, total 289 patients of HIV-2 were enrolled. A majority of them 158 (54.7%) belonged to the age group of 41 to 50 years and the median (IQR 25%-75%) age was 46 (42-51) years. Of the 289 individuals analyzed, 203 (70.24%) were males and 86 (29.76%) were females. Male to female ratio was 2.4:1. Thus, in our study prevalence of HIV-2 was more in male as compared with female. This may be due to high risk behaviour in male individual. In our study, out of 289 HIV-2 patients 223 (77.16%) were married, 19 (6.57%) were unmarried and 47 (16.26%) were widow and widower.

 

Table 1: Distribution of study population according to baseline CD4 count

In the present study, we evaluated the study population according to baseline CD4 categories and we observed that, maximum cases (238, 82.35%) had baseline CD4 count in between 51 to 350 cells /μl. 40 (13.84%) cases had CD4 count >350 cells /μl and 11 (3.81%) cases had CD4 count ≤50 cells /μl. Median baseline CD4 count of study population was 211 (123.7-303.2 cells /μl).

 

Fig. 1: Median baseline CD4 count of study population

In our study, 141 (48.79%) cases belonged to WHO stage I while 35 (12.11%) cases belonged to WHO stage II, 60 (20.76%) cases belonged to WHO stage III and 53 (18.34%) cases belonged to WHO stage IV indicating slower progression of HIV-2 infection as maximum cases were had WHO stage I category.

In our study, patients received ART regimen of 2 NRTIs (zidovudine / tenofovir + lamivudine) and Ritonavir boosted Lopinavir which is the regimen of choice for HIV-2 as these patients are inherently resistant to NNRTI (efavirenz / nevirapine); as a part of National Programme through our centre of excellence. In the study by Chiara M et al,¹⁰ there was a comparison of immunological response between HIV-2 patients who received 3NRTIs and 2 NRTIs and PIs. It was observed that CD4 counts of HIV-2 patients improved satisfactorily on 2 NRTIs and PIs than with 3NRTIs. In the present study, we found same results in patients on 2 NRTIs and PIs.

 

CONCLUSION

There was statistically significant correlation between WHO clinical staging and immunological status (CD4 count) of HIV-2 individuals. An increase in median CD4 count at 6 months and 12 months from the baseline median CD4 count was observed. The response to ART and the pattern of resistance to ART is unique; and further studies should be carried out for the same.

 

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