Rev Romana Med Lab. 2013;21(2):217-224. DOI:10.2478/rrlm-2013-0010

Sex differences in HIV-1 viral load and absolute CD4 cell count in long term survivors HIV-1 infected patients from Giurgiu, Romania.

Loredana Manolescu, MD, PhD, assistant professor of microbiology, virology and parasitology,1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Paul Marinescu, MD, HIV/AIDS coordinator for Giurgiu Count, Public Health Direction, Giurgiu, Romania

 

ABSTRACT

Introduction: Prior studies assessing sex differences correlated with the levels of human immunodeficiency virus (HIV)  RNA and absolute CD4 cell count in adults and children, treated or untreated with antiretroviral (ARV) therapy presented conflicting results.

Objective: To assess comparative HIV RNA levels and absolute CD4 cell count for men and women from a large cohort of HIV-infected long term survivors patients.

Methods:  462 HIV infected patients were analyzed cross-sectional and longitudinal after splitting into three groups: 156 naïve deceased patients, median age at death 10 years, 197  ARV treated patients, median age 17 years and 109 ARV treated patients,  median age 23 years followed up until 2011. HIV RNA and absolute CD4cell count were measured in all patients enrolled in the study.

Results: In cross-sectional analysis of 156 naïve patients HIV RNA median levels were lower in female comparing to  male, 4.95 vs. 5.73 HIV RNA log10 (copies/ml). Female absolute CD4 cell count was slightly higher, (median 97 vs. 65.5 cells/µL; P = .0001). Cross-sectional analysis of 197 ARV treated patients showed one log10 HIV RNA lower level for female comared to male, (P=.0001), also median CD4 count values lower for women, 336 cells/µL vs 456 cells/µL in men, P=.0001. Longitudinal analysis revealed statistically significant results: mean log viral loads were lower for female (F=13.90, P= .0009) and absolute CD4 cell count was lower for male (F=16.72, P<.0001), almost across all tested ages.

Conclusion: We report steady sex differences in HIV RNA levels and absolute CD4 cell count in ART-treated HIV-infected patients, a fact that may suggest a reevaluation of our  current treatment strategies according to sex.

 

SUPPLEMENT:

To further evaluate the effect of sex on age –related changes in HIV RNA level, a linear regression model with use of longitudinal data from group three was developed. A total of 109 HIV infected patients 23 years, median age at the end of 2011, were retrospectively followed up for their HIV RNA level and absolute CD4 cell count over a period of seventeen years. All this time the patients were heavily ARV treated, the median number of ARV regimens was 3 (limits: 2-5 regimens). HIV RNA level and absolute CD4 cell count were determined by regular basis follow up once a year, median number of evaluation was 9 (range, 3–13). We found that mean log viral loads were lower for female gender and higher for male gender almost across all ages tested and followed a common slope pattern (F= 0.265, P=.6102); (Figure 1). The differences between sexes were extremely significant (F=13.90, P= .0009) showing a variation of more than 2 log10 for male participants, mean difference 0.9 log10 copies/ml, (limits: 0.23-2.1 log10 copies/ml). Linear regression analysis of absolute CD4 cell count similarly showed an extremely significant difference between sexes (F=16.72, P<.0001), female patients had higher absolute CD4 cell count mean difference 103 cells/µL, (limits: 9-321 CD4 cells/µL) across all tested ages (Figure 2).

Loredana Manolescu-fig1Figure1. Linear regression lines showing the relationship of mean HIV RNA levels (log10 copies/mL) to age in male and female patients followed longitudinally in group three. HIV RNA levels were lower among female participants across all observed ages.

 

Loredana Manolescu-fig2Figure 2. Linear regression lines showing the relationship of absolute CD4 levels (cells/µL) to age in male and female patients followed longitudinally in group three. Absolute CD4 count was higher among female participants across all observed ages.

 

Even if nowadays in our country and throughout Eastern Europe we have access to high standard tests such as sequencing and genotyping and when starting or changing ARV therapy we take into account resistance mutations or transmitted drug resistance, we must never forget the importance of two simple tests: viral load – HIV RNA levels and absolute CD4 cell count, tests that remain the key laboratory measures used to guide initiation and monitoring of ART. Here we analyzed the differences between these tests according to gender on a unitary cohort of subjects within the same interval of age considered to be long term survivors, revealing that differences in HIV viral load and absolute CD4 cell count between male and female individuals are evident and steady from childhood to adult age.

A recent study (1) found substantial differences in HIV RNA level and CD4 cell percentages between naive HIV-infected boys and girls throughout childhood and before the onset of puberty suggesting that sex hormones are unlikely to be the major driver of the sex disparity in HIV RNA levels.

Prior studies on ARV treated HIV infected individuals clearly established sex differences in HIV RNA levels and CD4 cell parameters among adults but have also presented conflicting results (2,3). There is one study of 158 children receiving ART that found HIV RNA levels to be 0.38 log lower in girls than in boys but found no difference in CD4 cell count or percentage (2). But there are few studies that analyzed differences on HIV RNA level and CD4 cell count in a large number of participants and no one over such a long period of time.

For our study we drew data from a large cohort of children, a total of 462 HIV infected patients analyzed into three groups. 33.76% of the patients were naïve to ARV and 66.23 were ARV experimented. Out of the treated patients 30.62% patients were longitudinally followed up for more than seventeen years. Our cohort is representative because the participants are from the same region, are infected in the same way and were subjected to the same behavioral and epidemiologic risk factors or socioeconomic disparities. The majority of patients came from HIV/AIDS uninfected parents.

Our patients clearly present lower HIV RNA levels in female comparing to male participants in all groups, ARV naïve or treated and by all types of analysis: cross-sectional and longitudinal.  Regarding the absolute CD4 cells count, in cross sectional analysis, the levels of CD4 cells were for females slightly elevated in ARV naïve patients group and lower in ARV treated patients group. In longitudinal analysis the difference between sexes was evident and statistical significant: female participants presented higher absolute CD4 cell count levels.

Because the differences in HIV RNA levels according to sex occurred over a sustained period in time, seventeen years, but were higher in early ages, a change toward the viral threshold for initiation and change of therapy in female children may be considered, with research that shows therapy to be most beneficial when started early. Also under treatment on this segment of population must be taken into account.

In resource-limited settings it may not be feasible to perform viral load testing very often. The absolute CD4 count may be an alternative used to evaluate and choose the moment of therapy change. Differences between gender with regard to this parameter must be considered.

 

REFERENCES

1.Ruel TD, Zanoni BC, Ssewanyana I, Cao H, Havlir DV, Kamya M, et all. Sex Differences in HIV RNA Level and CD4 Cell Percentage During Childhood. CID 2011; (53) :592-599.

2. Foca M, Moye J, Chu C, Matthews Y, Rich K, Handelsman E et al. Gender differences in lymphocyte populations, plasma HIV RNA levels, and disease progression in a cohort of children born to women infected with HIV. Pediatrics 2006; (118):146–155.

3. European Collaborative Study. Are there gender and race differences in cellular immunity patterns over age in infected and uninfected children born to HIV-infected women? J Acquir Immune Defic Syndr 2003; (33):635–641.

 

Contact:

Loredana Manolescu, MD, PhD

Assistant Professor of Virology

Carol Davila University of Medicine and Pharmacy

Bd. Eroilor Sanitari Nr. 8, Bucharest, Romania

email: manolesculoredana@yahoo.com

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