|Year : 2015 | Volume
| Issue : 1 | Page : 78-83
Current scenario of Opportunistic and co-infections in HIV-infected individuals at a tertiary care hospital in Mumbai, India
VR Chavan1, V Chaudhary1, P Ahir1, R Mehta2, PS Mavani3, C Kerkar1, JM Pramanik1
1 Department of Infectious Diseases Biology , National Institute for Research in Reproductive Health, Parel, Mumbai, Maharashtra, India
2 Department of Microbiology , Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai, Maharashtra, India
3 Department of Obstetrics and Gynecology , Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai, Maharashtra, India
|Date of Submission||03-Sep-2013|
|Date of Acceptance||17-Feb-2014|
|Date of Web Publication||5-Jan-2015|
J M Pramanik
Department of Infectious Diseases Biology , National Institute for Research in Reproductive Health, Parel, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Purpose: An update on opportunistic infections/co-infections (OIs/CIs) is essential to understand the success of highly active antiretroviral therapy offered by the government agencies in reducing AIDS-related OIs/CIs. Hence, the present study aimed to evaluate the frequency of OIs/CIs in HIV-positive individuals at a tertiary care hospital in Mumbai. Its' association with CD4 counts, anti-retroviral treatment and on HIV transmission was also determined. Materials and Methods: An observational study was designed to evaluate different OIs/CIs in individuals, who tested positive for HIV infection at the ICTC/Shakti Clinic of Seth G.S. Medical College and KEM Hospital, Mumbai. Data analysis was done with the use of SPSS software (version 19.0, SPSS, Chicago, IL, USA). P value was considered significant if it is < 0.05. Results: Heterosexual contact was the major route of transmission among the enrolled 185 individuals. Ninety (48.06%) HIV-infected individuals were with OIs/CIs. Tuberculosis (TB) was the most common OI (68.8%). Other CIs noted were Herpes zoster, syphilis, hepatitis C and B, malaria, typhoid and dengue. The median CD4 count in HIV-positive individuals with TB was 337 ± 248 cells/μl, and 67.7% of individuals with OIs/CIs had low CD4 counts (<400 cells/μl). Individuals in 31-40 years of age group had significantly (P = 0.01) more OIs/CIs. More (53.7%) spouse/children of HIV-positive individuals without OIs/CIs were HIV-1 positive. Low proportions of individuals with or without OIs/CIs were on ART. Conclusion: Nearly half of HIV-infected individuals were with OIs/CIs. Initiation of free ART programme since 2004 possibly associated with the type and rate of OIs/CIs. Tuberculosis and multiple OIs/CIs were associated with low CD4 counts. Infection was high in 31-40 years age group. Most of the spouses of individuals without OIs/CIs were HIV positive, indirectly indicates lack of condom use or lack of awareness of condom use.
Keywords: ART, CD4 counts, co-infections, HIV, opportunistic
|How to cite this article:|
Chavan V R, Chaudhary V, Ahir P, Mehta R, Mavani P S, Kerkar C, Pramanik J M. Current scenario of Opportunistic and co-infections in HIV-infected individuals at a tertiary care hospital in Mumbai, India. Indian J Med Microbiol 2015;33:78-83
|How to cite this URL:|
Chavan V R, Chaudhary V, Ahir P, Mehta R, Mavani P S, Kerkar C, Pramanik J M. Current scenario of Opportunistic and co-infections in HIV-infected individuals at a tertiary care hospital in Mumbai, India. Indian J Med Microbiol [serial online] 2015 [cited 2019 Jul 19];33:78-83. Available from: http://www.ijmm.org/text.asp?2015/33/1/78/148386
| ~ Introduction|| |
India currently harbours 20.89 lakh HIV-infected patients.  Opportunistic infections (OIs) and cancers have been recognised as common complications of HIV infection. Overall incidence of OIs increases as immune suppression in HIV infection progresses. Most of the time, OIs constitute the first manifestation of HIV infection, indicating significant immunodeficiency.  A steady decrease in CD4 count is responsible for the profound immune deficiencies that lead to various OIs in the HIV-infected patients. 
The widespread use of effective chemoprophylaxis for these infections and, more recently the use of antiretroviral therapy have resulted in delay in the onset of AIDS, longer survival and a change in the pattern of OIs in developed world. , Region-wise statistics on opportunistic and co-infections (OIs/CIs) in HIV-infected individuals varies from different parts of the country. , Although reports are available from the city of Mumbai on OIs/CIs, where many HIV prevention and management programmes are in place, ,,,,, these findings were confined or limited to only one CIs/OIs, such as CIs between HIV and HCV  ; HIV infection in TB cases  or HIV in malaria cases;  syphilis prevalence among HIV patients,  except one report on multiple OIs/CIs among HIV-infected paediatric populations.  An update on different OIs/CIs may further add to the effective implementation of the present programmes on HIV managements. It is necessary to know whether the earlier reported spectrum of OIs/CIs has changed after the implementation of free-ART programme in Mumbai since 2004. Hence, present study aimed to record different OIs/CIs in individuals who tested HIV positive, at a tertiary care hospital in Mumbai. Its association with CD4 counts, anti-retroviral treatment and on HIV transmission was also determined.
| ~ Materials and Methods|| |
An observational study was designed to record different OIs/CIs in HIV individuals who were detected with HIV infection at the Integrated Testing and Counselling Centre (ICTC/Shakti Clinic), Department of Microbiology, of Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai during the year 2008-2011.
The study was approved by the institutional/hospital ethics committee. Earlier reports (North India: 55.2% and South India: 68.5%) , on HIV and tuberculosis (TB) were taken into consideration while calculating the sample size using the standard formula.  In the present study, TB and pneumonia was considered as OIs whereas other infections such as Herpes Zoster, hepatitis B and C, syphilis, malaria, typhoid amd dengue were considered as co-infections (CIs). Before HIV testing, each individual underwent pre and post-test counsellors with demonstration of condom use for protection/transmission of infection in couples. Inclusion of individuals was based on willingness of couples to undergo HIV testing and at least one or both of them was detected with HIV infection and positive mothers who delivered during this period and willing to enroll her infants for HIV screening at regular intervals. Enrolment was a consecutive process, where those individuals who gave written consent were enrolled. Patients who refused to give consent for further investigations were excluded from the study. Blood samples (Plain and EDTA) 3-5 ml was collected from each enrolled individual. Patient details such as demographic characteristics, present and past history of OIs/CIs were recorded.
Diagnosis of opportunistic and co-infections
Specific OIs/CIs were diagnosed on the basis of standard clinical definitions and by routine serological and microbiological tests at Department of Microbiology. HIV antibodies were tested by three rapid tests with different antigens/principles (Testing strategies III) as recommended by National AIDS Control Organization (NACO) guidelines, Ministry of Health and Family Welfare, Government of India.  Antibodies to HIV (1 and 2) were tested initially using COMBAIDS-RS Advantage (Span Diagnostics Ltd, Surat, India), samples found positive were tested by Pareekshak HIV ½ Triline card test (Bhat Bio-Tech India (P) Ltd, Bangalore, India) and Pareekshak (Trispot) (Bhat Bio-Tech India Pvt Ltd, Bangalore, India). TB diagnosis was done on the basis of smear microscopy, chest radiography and clinical signs and symptoms as per the Revised National Tuberculosis Control Programme (RNTCP).
Syphilis infection was detected using Trepolipin: Modified VDRL reagent (Tulip Diagnostics Pvt Ltd, Goa, India). Hepatitis C antibody was detected using SD HCV ELISA 3.0 (SD Bio standard diagnostics, Pvt Ltd, Haryana, India), while Hepatitis B surface antigen (HBsAg) detection was done using HEPALISA (J Mitra and Co Pvt Ltd, New Delhi, India). Malaria infection was tested using ACCUCARE TM One Step Malaria Pf/Pv Antigen Test (Lab-Care Diagnostics India Pvt Ltd, Valsad, India). Dengue antigen and differential IgG/IgM antibody detection was done using SD Dengue NS1 Ag + Ab Combo (Standard Diagnostics, INC, Korea), while Herpes zoster and typhoid antibody (tested in private laboratory) result were noted from the individual's clinical report. CD4 count was estimated using BD FACS Calibur flow cytometer (Becton Dickinson and San Jose, USA).
Data entry and data analysis was done with the use of SPSS software (version 19.0, SPSS, Chicago, IL, USA). Average, percentage, median and standard deviation were calculated using descriptive statistics. Z-test was applied to calculate significant difference in proportion of individuals present in different age groups as well as between discordant couple (DC) and both positive (BP) with or without OIs/CIs. Difference in CD4 count was tested using independent sample t-test. P value was considered significant if it is < 0.05.
| ~ Results|| |
The demographic details of enrolled individuals with (n = 90, 48.6%) or without (n = 95, 51.4%) OIs/CIs are presented in [Table 1]. Among the enrolled 185 HIV-positive individuals (males: 93; females: 92), 109 from ICTC and 76 referred from PPTCT centre of the Hospital. Heterosexual contact (61.08%) was the major route of HIV infection, while 33 individuals (25 females and 8 males) expressed their ignorance on route of acquisition of the infection. Other routes of transmission was likely through blood transfusion (9.1%) as said by the participants (Male: 7; Female: 10), needle prick (4.8%) or from mother to child (7.02%). During counselling it was noted that all of them had unprotected sexual relationship with their spouse or did not consistently use protective methods such as condom. TB was the most common OIs (75.6%) while Herpes Zoster (6.6%) and syphilis (5.5%, VDRL positive) were common CIs. Only TB was seen in 62 (33.5%) and another 6 had TB with Herpes Zoster (n = 4) or with Hepatitis B virus (n = 2). There were individuals in the study which had more than one OIs/CIs and referred as multiple OIs/CIs (n = 6; 6.7%). One patient had pneumonia of Streptococcus pneumonia aetiology [Figure 1].
|Figure 1: Opportunistic and co-infections in HIV-positive individuals (n = 90), TB = Tuberculosis, HZ = Herpes Zoster, HCV = Hepatitis C Virus, HBV = Hepatitis B Virus, MOIs/CIs = Multiple opportunistic/ co-infections|
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|Table 1: Demographic details of HIV - positive individuals enrolled in the study|
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OIs/CIs frequency were significantly high in 31-40 (69.4%) years of age group, significant proportion of males were with OIs/CIs compared females [Figure 2]. Average median CD4 count in individuals as well as in males and females with different OIs/CIs is given in [Figure 3]. The average ± SD of median CD4 values of individuals with OIs/CIs was 349 ± 256 cells/μl, whereas it was 536 ± 320 cells/μl for those without any OIs/CIs. There was no statistical difference in CD4 counts of individuals with TB compared with other CIs (P = 0.251) at 95% CI. Low CD4 count was significantly associated with high infections [Table 2]. None of them have cytomegalovirus, cryptococcal or oral candidiasis.
|Figure 2: Age-wise distribution of HIV-positive individuals with or without OIs/CIs (n = 185) *with or without OIs/CIs; Z = 2.9, P < 0.01; # comparison between males and females with OIs/CIs; Z = 7.04; P < 0.001|
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|Figure 3: Opportunistic and co-infections and there correlation with median CD4 counts. TB = Tuberculosis, HZ = Herpes Zoster, HCV = Hepatitis C Virus, HBV = Hepatitis B Virus, MOIs/CIs = Multiple opportunistic/co-infections, OIs/CIs = Total opportunistic/co-infections|
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Among individuals with OIs/CIs, 45.6% were on antiretroviral therapy (ART) while 36.8% of individuals without any OIs/CIs were on ART. Among the individuals with OIs/CIs, 73.3% of their spouse/children were HIV seronegative, and they remained as discordant couples/children (DC); while 69.5% of those without OIs/CIs had positive spouse/children (Both positives, BP). Infection in spouse/children of HIV-positive individuals with or without OIs/CIs and their ART status is presented in [Figure 4].
|Figure 4: HIV status of spouse/children of HIV-positive individuals with or without OIs/CIs and ART *Z = 5.9, P < 0.001 # Z = 6.5, P < 0.001|
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| ~ Discussion|| |
Current study revealed a low frequency of OIs/CIs (48.6%) among the HIV-infected individuals, compared to previous reports from India. , Tuberculosis as an only OI (33.5%) or with other CIs such as Herpes zoster or with Hepatitis B virus (36.8%) was also found to be too low compared to earlier studies on HIV-positive South Indian populations , or North Indian population.  In the present study TB diagnosis was done as per the RNTCP guidelines, therefore, it ruled out the false negatives. Low TB infection observed might be due to better implementation of RNTCP programme at this particular tertiary care referral teaching hospital.
CIs of TB such as Herpes zoster (2.2%), was similar to North Indian (2.5%) HIV-infected population but comparatively low as reported in two populations (14.7% or 8.6%) of Southern India. ,, This difference emphasizes further, strengthening of the HIV-care programmes in South India or update of report from this population.
The World Health Organization (WHO) recently recommended, HBV testing of each patient infected with HIV before initiation of ART.  We have reported 4.4% of HBV co-infection in HIV-infected population, one reason for low Hepatitis B infection, could be due to low prevalence of HBV in local Mumbai population (0.62 − 4.7%). 
The report on Hepatitis C infection in HIV patients in India has been very varied. In Southern Indian HIV-infected population, sero-prevalence of HCV was 21.4% in STD clinic  ; while in other set up the frequency varied from 4.8% to 6.0%.  However, a study in rural population (n = 1054) in Maharashtra indicated a prevalence of 0.09% HCV.  This might be the reason why, HIV and HCV co-infection was low (1.1%) in our studied population.
Sexually transmitted infections (STI's) are generally known to increase the risk of HIV transmission by modifying the natural history of HIV disease.  Syphilis infection was seen in 5.5% of infected individuals. This was found to be low as compared with earlier reported prevalence of 9.1% from a similar tertiary care referral teaching hospital from Mumbai.  This decrease in rate with time might be due to further improvement in HIV prevention and associated programmes of NACO,  supported with recent reports on low syphilis rate (3.5%) in HIV-infected population. 
Not a single patient from our study was reported with cryptococcal infection, which was reported earlier in HIV-infected populations from Mumbai. , These studies were conducted before free-ART era. ART is available free of cost from April 2004 at all the ART centres across India including ours. The World Health Organization (WHO) recommends cryptococcal antigen screening in HIV-infected persons with CD4 count of <100 cells/μl, who are more prone to cryptococcal infections.  None of our enrolled patient was having CD4 count of <100 cells/μl, might be the other possible reason for absence of cryptococcal infection.
While diagnosing OIs/CIs, we came across few HIV patients with infections like dengue, malaria and typhoid. These infections might be situation specific, depending on their living conditions. Except the dengue patient, CD4 counts of these patients were low and might be at risk as reported in South African population.  High CD4 count in dengue patient might be due to the activation of CD4 + and CD8 + T cells in dengue haemorrhagic fever. 
When CD4 counts of these individuals with or without OIs/CIs were taken into consideration, irrespective of their ART status, 20.8% had a low CD4 count (<200 cells/μl) and 78.1% of these had OIs/CIs. With increase in CD4 counts, the OIs rates decreased, significant proportion of individuals with low CD4 count had high frequency of infection. However, CD4 counts observed in individuals with Herpes zoster, HCV or even among the TB co-infected individuals was more compared to earlier studies either from North  or Western Indian population. , This indicated availability of a better health care facility with time.
Significantly high (Z = 2.9, P = 0.01) proportion of patients in 31 − 40 years age group were with OIs/CIs might be due to their active sexual life. This age group was also with high rate of OIs/CIs in HIV sero-positive patients in South/Eastern Indian Population. ,,
Heterosexual contact was found to be the major route (61.1%) of transmission of HIV in our study, which was consistent with the findings of North or Eastern Indian populations. , Otherwise, the rate was less compared to earlier findings (75-95%). ,, Major changes for the good have occurred over the last decade due to awareness programmes. High proportion of individuals with unknown (UK 17.8%) cause of HIV acquisition could be the possible reason for low rate of heterosexual transmission in our studied population. The individuals questioned by trained personal either had lied or were ignorant on cause of infection. The other avoidable route of transmission is safe blood transfusion. However, rate of HIV transmission through blood transfusion was high compared to 2% reported in the earlier autopsy study from Mumbai  or in North (5.5%) and South Indian (4.6%) population or as reported by NACO (3.8%). ,, Although no report was available on blood transfusion in the enrolled participants, their verbal report was taken into consideration as the route of HIV transmission. Several programmes are in place in India to restrict HIV transmission through blood transfusion; present observations suggest making it more stringent to prevent transmission of any infection through the use of contaminated blood.
We also compared infections in spouse/children among those with or without OIs/CIs and with or without ART. Among those with ART and OIs/CIs, infected spouse/children number was significantly low compared to those without OI/CIs. Similarly, number of infected spouse/children was significantly high in those without ART or OIs/CIs, compared to those with OIs/CIs. This indicated that absence of ART; transmission to infants was more, or absence of OIs/CIs, the sexual activities remain unaffected or indirectly indicates lack of condom use or lack of awareness of condom use leading to infection in spouse.
Earlier reported studies from Mumbai on OIs/CIs were before free ART era. With the initiation of free ART programmes since 2004, the pattern of OIs/CIs might have changed as observed in our study.
| ~ Conclusions|| |
Present study highlights low rate of different OIs/CIs among the HIV-infected individuals attending a tertiary care hospital in Mumbai. Initiation of free ART programme since 2004 possibly associated with the type and rate of OIs/CIs. With or without ART, levels of CD4 counts were comparatively more than reports from other Indian studies. OIs/CIs were found more commonly in 31-40 years age group and with low CD4 count. Significantly high numbers of spouse and children of individuals without OIs/CIs were with HIV infection.
| ~ Acknowledgement|| |
Financial support from Indian Council of Medical Research (95/7/388/2009-RHN) and Department of Biotechnology (BT/PR10101/Med/29/55/2007), Government of India is acknowledged.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]