1. Texas Pediatric Society Electronic Poster Contest
Non Elite
Elite
Pre-therapy Absolute CD8#
1000
2000
3000
4000
5000
Non Elite
Elite
Pre-therapy CD4% 20 40 60 80
100
Non Elite
Elite
Pre-therapy CD8% 20 30 40 50 60 70 80 90
Non Elite
Elite
Pre-therapy Absolute CD4#
200
400
600
800
1000
1200
1400
Study of Elite HIV Viral Controllers in Pregnancy
Koshy Marucoickal George, MD a (PGY-3); Janak Patel, MD ab; Department of Pediatrics a, Division of Pediatric Infectious Diseases b. University of Texas Medical Branch, Galveston, Texas.
Abstract
Table 3: Pre-Therapy Virologic and Immunologic Factors
Background: The incidence of elite controllers is very low in the general HIV+ population (<1%), however, the incidence in a largely asymptomatic population of HIV+ pregnant women is not known.
Objectives: Determine the incidence of elite controllers in HIV+ pregnant women, and to analyze its relationship with demographic and socioeconomic factors, as well as immunologic CD4 and CD8 markers.
Study Design: We conducted a retrospective medical chart review of HIV+ pregnant women (study period 2007 to 2014) who had not been on antiretroviral therapy (ART) prior to pregnancy.
Results: Among 192 HIV+ women, the elite controllers incidence was 15.6%. Demographic and socioeconomic factor did not contribute to the elite controller status. Prior to initiating ART, absolute CD4, CD4%, CD8% & CD4/CD8 ratio were significantly different in elite controllers compared to non-elite controllers. While on ART, immunologic markers did not change significantly in elite controllers, while all of them changed in non-elite controllers. There was no perinatal HIV transmission in either group.
Conclusion: Elite controller status in pregnant women is far more common than in previously published studies of the general HIV+ population. Additional studies are needed to identify other immunologic/genetic markers and virologic factors that contribute the high elite controller status in this population. .
635 32
365 25
P<0.001
p<0.001 52 43
795
764
p<0.625
p<0.001
Introduction
Non Elite
Elite
Pre-therapy CD4/CD8 Ratio
0.0
0.5
1.0
1.5
2.0
Most individuals infected with human immunodeficiency virus (HIV) in the absence of antiretroviral therapy (ART), exhibit persistent virus replication and declining CD4+ cell numbers over time and develop AIDS.
‘Elite controllers’ are individuals with HIV infection who naturally maintain undetectable plasma virus loads while remaining asymptomatic without ART 1.
While the mechanisms underlying the elite controller status are under investigation, host genetic and acquired factors, as well as specific viral characteristics, are known to contribute to viral containment1,5.
In the general population of HIV infected adults, the incidence of elite controllers is <1% 1,6, however, the incidence of elite controllers, using ultrasensitive assays, in pregnant women has not been studied. The viral control mechanisms could be different in pregnant women because of either the gender (female) or the immune alterations due to pregnancy related hormonal changes7. Understanding the factors associated with HIV control during pregnancy may help develop additional strategies for perinatal prevention of HIV & provide important information regarding pathogenesis, vaccine strategies and development of novel therapeutic agents to combat HIV1.
SPECIFIC AIMS
Describe the incidence of elite and non-elite controllers in pregnant women who have confirmed HIV infection by Western blot assay.
Analyze factors in relation to the elite controller status:
Demographic and socioeconomic factors: Age3, race/ethnicity3, parity 3, education, substance abuse3, employment status.
Immunologic markers: Absolute CD4 and CD8 count and percent, CD4/CD8 ratio3,4, before and after initiation of ART.
0.75
0.5
p<0.001
Table 3: Change in Virologic and Immunologic factors after treatment
Pre Treatment
Viral Load
On-Treatment
P value
(Rank sum test)
Elite 74
0.39
Non Elite
16762
<0.001
CD4 absolute
635
602
0.29
365
456
0.006
CD4 %  32 34
0.14 25 29
0.005
CD8 absolute
764
647
0.16
795
675
0.032
CD8 %
42.5
42.0
0.64 52 49
0.04
CD4: CD8 ratio
CD4: CD8 ratio  
0.75
0.8
0.41
0.5
0.6
0.002 .
Description of study
Type of study: Retrospective medical chart review study of HIV+ pregnant women who were evaluated at the UTMB Maternal-Child HIV Program.
Study period: 2007 to 2014.
Inclusion criteria:
All HIV+ pregnant women seen throughout pregnancy.
Exclusion criteria:
Women with congenital HIV infection, lack of follow up, miscarriages, or transfer of care.
Definitions:
Elite controller: Elite controllers are subjects with HIV viral load less than 75copies/ml (“ undetectable HIV load ” ) in the absence of ART.
Non-elite controller: Non Elite controllers are those with viral load >75copies/ml in the absence of ART. :
Conclusions
Summary of Results
The elite controller incidence of 15.6% in our HIV+ pregnant women population is significantly higher than previously published studies which show an incidence of <1%.
Demographic and socioeconomic features of these women do not contribute to the elite controller status although white women are less likely to be elite controllers.
Prior to initiating ART, absolute CD4, CD4%, CD8% and CD4/CD8 ratios are significantly different in elite controllers compared to non-elite controllers.
After initiation of ART, CD4, CD8, CD4%, CD8% and CD4/CD8 ratio do not change significantly in elite controllers while all of these change in non-elite controllers.
Implications
Additional studies are needed to identify other immunologic/genetic markers and virologic factors that contribute to the high elite controller status in pregnant women.
Additional understanding of the elite controller status in pregnant women may allow selective ART strategies for perinatal HIV prevention.
Results
240 HIV+ pregnant women were identified.
48 women were already on ART prior to prenatal care (excluded from further analysis).
192 patients were not on ART prior to pregnancy.
30 (15.6%) were elite controllers.
162 (84.4%) were non elite controllers.
Regardless of controller status, all women were placed on ART for prevention of perinatal HIV.
None of the women transmitted HIV to their newborn infants (100% prevention).
From the date of diagnosis of HIV, the mean period of elite controller status was 11 months. Range = 2 wks to 13 years.
Table 1: Demographic and Socioeconomic Factors
Elite ( n= 30)
Non Elite( n= 192)
P value*
Age in years (median)
24.5 26
 0.218
Race
Black
21 (70%)
92 (57%)
0.17
Hispanic
6 (20%)
30 (19%)
White
3 (10%)
39 (24%)
Asian
1 (1%)
Gravida
Primi
7 (23%)
54 (29%)
0.28
Multi
23 (71%)
108 (71%)
Marital
Single
24 (80%)
129 (80%)
0.96
Married
33 (20%)
Education
CHS
10 (33%)
75 (75%)
0.19
NCHS
20 (67%)
87 (87%)
Employment No
22 (73%)
109 (67%)
0.51
Yes
8 (27%)
53 (33%)
Substance abuse
13 (57%)
68 (58%)
0.89
17 (43%)
94 (42%)
*P values calculated by Rank Sum test for age, and others were by Chi square test
CHS = completed high school; NCHS = not completed high school.
References
1. Olson, A. D., (2014) .An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration. PLoS ONE, 9(1).
2. Morris, A. B.,(2005). Protease inhibitor use in 233 pregnancies. Journal of Acquired Immune Deficiency Syndromes 40(1), 30–3.
3. Madec, Y., (2010). Undetectable viremia without antiretroviral therapy in patients with HIV seroconversion: an uncommon phenomenon? Clinical Infectious Diseases.  : An Official Publication of the Infectious Diseases Society of America, 40(9), 1350–4.  
4. Rutland, E., (2010). Management of pregnancy in an HIV elite controller. International Journal of STD & AIDS, 21(8), 604–605
5. Saag, M., (2010). How Do HIV Elite Controllers Do What They Do? Clinical Infectious Diseases, 51(2), 239–241.
6. Okulicz, J. F., (2009). Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. The Journal of Infectious Diseases, 200(11), 1714–1723.
7. Ekouevi, D. K., (2007). Variation of CD4 count and percentage during pregnancy and after delivery: implications for HAART initiation in resource-limited settings. AIDS Research and Human Retroviruses, 23(12), 1469–74.
8. Chama, C. M., (2009). Normal CD4 T-lymphocyte baseline in healthy HIV-negative pregnant women. Journal of Obstetrics and Gynaecology, 29(8), 702–704.
Table 2: HIV viral load range at first visit (pretherapy)
Viral Load
Frequency
0-75 30
Elite controllers 15.6%  
76-100 3
Non Elite controllers 84.4% 4 5 13 27
,000 57
,000 41
>50,000 12
Texas Pediatric Society Electronic Poster Contest