Characteristics of treatment-naive human immunodeficiency virus type 1 seropositive individuals with undetectable plasma viral load

Citation metadata

Date: January-March 2018
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 2,223 words
Lexile Measure: 1540L

Document controls

Main content

Full Text: 

Byline: Paotinlal. Haokip, Rebachandra. Heigrujam

BACKGROUND: Undetectable plasma human immunodeficiency virus type 1 (HIV-1) viral load means the virus load is lower than the detection limit of the assay used, but it does not imply the absence or clearance of the virus from the blood. This study was undertaken to analyze the various characteristics of HIV-1 seropositive antiretroviral therapy (ART)-naive individuals with undetectable plasma viral load (PVL). MATERIALS AND METHODS: The present cross-sectional study was conducted on 82 treatment-naive individuals in a tertiary care teaching institute in Northeast India, from October 2014 to September 2016. PVL was determined by COBAS[R] TaqMan[R] HIV-1 test version 2.0, and CD4+ T-lymphocytes' count (CD4 count) was estimated by Fluorescent-Activated Cell Sorter Count&#8482; System. Statistical Package for the Social Sciences software version 16.0 was used for all statistical analyses. Variables were expressed as median, interquartile range, and percentage. P < 0.05 was considered statistically significant. RESULTS: PVL was not detectable in 8.5% of ART-naive individuals whose data contributed to these analyses. All the participants were clinically asymptomatic (100%), educated (100%) and majority of them were married (71.4%), and unemployed (85.7%). The CD4 counts ranged from 453 to 1225 cells/[micro]L, with a median CD4 count of 706 cells/[micro]L. The median CD4 count was 776 cells/[micro]L and 671 cells/[micro]L in the males and females, respectively (P = 1.00). CONCLUSIONS: ART-naive HIV-1 seropositive individuals with undetectable PVL have a normal CD4 count and no significant gender difference in the median CD4 count.

Introduction

The human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) in plasma, called plasma viral load (PVL),[1] indicates the magnitude of virus replication,[1],[2] and it has been used as a guide to initiate and monitor antiretroviral therapy (ART).[3] All the commercially available HIV-1 viral load assays have a cutoff point below which they cannot reliably detect HIV-1, called detection limits. PVL is declared undetectable or target not detected if it is below 34 copies/mL of plasma (according to the COBAS [R] TaqMan [R] HIV-1 test, version 2.0),[4] but the exact number depends on the assay or laboratory performing the test.[3] Undetectable PVL reduces the risk of becoming ill because of HIV and the risk of passing on HIV-1 to someone else. Recent studies demonstrated a high rate of undetectable PVL among ART-naive HIV-positive individuals (elite controllers) ranging from 9.5% to 16%,[2],[5] but detailed characteristics associated with this group of individuals are rarely published. However, even in these groups of patients, there is a continual low level of virus replication due to a pool of persistent latently infected cells,[6] and no elite controller has ever eradicated the HIV-1.[7] Some of these individuals experience CD4+ T-lymphocytes' (CD4) loss and progression to clinical acquired immunodeficiency syndrome.[8]

This study was undertaken to analyze the various characteristics of HIV-1 seropositive ART-naive individuals with undetectable PVL. So far, there is no report of similar studies being conducted in North-east India, and these findings will be of great help to the medical professional in taking the right decision for the better management of ART-naive HIV-1-infected individuals with undetectable PVL.

Materials and Methods

This study was a cross-sectional study conducted in the Department of Microbiology of a tertiary care teaching institute in Northeast India from October 2014 to September 2016. It was approved by the Institutional Ethics Committee and written informed consent was obtained from all participants before enrollment. Eighty-two documented HIV-1-seropositive ART-naive individuals of age &#8805;15 years were enrolled in the study. 'ART-naive' patients were defined as an individual with HIV-1 seropositive but not yet taking ART. Patients with a history of any infection or immunization within the past 4 weeks were excluded from the study. Participants were requested to fill up a predesigned and pretested structured questionnaire. All the data collection forms were given a unique study number or code to remove any patient identifiers and to maintain privacy and confidentiality. About 3 ml of venous blood was collected in vacutainer tube from each individual under strict aseptic precautions. Fifty microliters of whole blood for CD4+ T-lymphocytes' count (CD4 count) estimation was immediately separated by reverse pipetting. Plasma was separated from the remaining blood sample within 6 h of collection and transferred to a sterile, 2 ml polypropylene screw cap tube. Five hundred microliters of plasma was used for viral load quantification. All the samples were processed according to the manufacturer's instructions.

CD4 count was estimated by the Becton Dickinson Company (BD) Fluorescent Activated Cell Sorter Count&#8482; (FACSCount&#8482;) System (BD Biosciences, San Jose, CA, USA). Plasma HIV-1 viral load (PVL) was determined with the COBAS [R] TaqMan [R] HIV-1 test version 2.0 (Roche Diagnostics, Branchburg, NJ 08876, USA) as described elsewhere.[4],[9] Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS, Chicago, Illinois, USA). Variables were expressed as median, interquartile range (IQR), and percentage (%). Median values were compared using the Mann-Whitney U-test. P < 0.05 was considered statistically significant.

Results

PVL was not detectable in seven of 82 (i.e., 8.5%) ART-naive individuals whose data contributed to these analyses. The age ranged in the study population was 16-45 years, of which most were males (57.1%). All the participants were clinically asymptomatic (100%), educated (100%) and majority of them were married (71.4%), and unemployed (85.7%). Mode of acquiring HIV infections was unprotected heterosexual contact (85.7%) and parent-to-child transmission (14.3%). Majority of the participants (57.1%) knew their HIV-1 positive status recently, i.e., within the past 6 months before this study was undertaken, whereas 42.9% were diagnosed as HIV-1 infected more than 12 months ago [Table 1]. There was no any clinical or documented evidence of any coinfections or opportunistic infections in these patients.{Table 1}

The CD4 counts ranged from 453 to 1225 cells/[micro]L, with a median CD4 count of 706 cells/[micro]L (IQR, 481-1006 cells/[micro]L). The median CD4 count was 776 cells/[micro]L (IQR, 453-1006 cells/[micro]L) and 671 cells/[micro]L (IQR, 519-1095 cells/[micro]L) in the males and females, respectively ( P = 1.00) [Table 2]. The median CD4 count of ART-naive patients with detectable PVL was 263 cells/[micro]L (IQR, 110-441 cells/[micro]L) [Table 3].{Table 2}{Table 3}

Discussion

In this study, we quantified plasma HIV-1 RNA and CD4 count of ART-naive HIV-1 seropositive individuals and focused our analysis on patients with undetectable PVL. Our analysis showed that the most commonly affected age group (i.e., 15-49 years) and the most common mode of HIV-1 transmission (i.e., heterosexual contact) in ART-naive individuals with undetectable PVL were similar to previously published reports.[10],[11]

PVL was not detectable in 8.5% of the ART-naive individuals which is in concordance with another similar study from Nigeria (9.5%).[2] Undetectable PVL indicates that the virus load is lower than the detection limit of the assay used, but it does not imply the absence or clearance of the virus from the blood. Even in this group of patients, there is a continual low level of virus replication due to a pool of persistent latently infected cells,[6] and no elite controller has ever eradicated the HIV-1.[7] Pereyra et al. demonstrated that low-level plasma viremia is present in the majority of elite controllers, with a median PVL of 2 copies/mL (IQR, 0.2-14 copies/mL).[12] Undetectable PVL could be due to a strong immune status of these patients as reflected by the high CD4 counts (median, 706 cells/[micro]L) or genetic variation in HIV-1 subtypes.[13] Re et al. documented that a high level of HIV-1 specific antibody against HIV-1 Tat peptides containing amino acid residues 6-14 (Tat 6-14), Tat 36-50, and Tat 46-60 was associated with an undetectable PVL.[14] Nevertheless, it is important to remember the fact that relatively high rates of CD4 count may be accompanied by a very high viral replication or a low PVL may be accompanied by low CD4 count.[5],[15]

We found that ART-naive HIV-1 seropositive individual with undetectable PVL had a median CD4 count of 706 cells/[micro]L which is in agreement with a similar study from Sweden (median CD4 count, 828 cells/[micro]L).[12] The previous study found that gender differences in CD4 counts persist after HIV-1 infection although the exact biological mechanisms remain unexplained.[16],[17] However, in our study, there was no significant gender difference in the median CD4 count ( P = 1.00) of ART-naive HIV-1 seropositive individual with undetectable PVL.

It was interesting to note that there was not a single opportunistic coinfection in ART-naive individuals with undetectable PVL, whereas the prevalence of HIV coinfections was 7.31% in ART-naive patient with detectable PVL. This could be due to a significantly higher median CD4 count in ART-naive individual with undetectable PVL compared to that of ART-naive individual with detectable PVL ( P = 0.019), suggesting the vital role of immune responses in controlling the virus replication and opportunistic infections. A better understanding of the meaning of undetectable PVL and the significance of immunological status in ART-naive individual with undetectable PVL is of paramount importance for the better management of these individuals.

There were certain limitations in our study. ART-naive status of the cases was obtained by self-report of each individual, thus there is potential for some patients on ART for a variable period. Follow-up study of ART-naive patient with undetectable PVL was not done and therefore, how long these individual PVL remains undetectable cannot be ascertained.

Conclusions

ART-naive HIV-1 seropositive individuals with undetectable PVL have a normal CD4 count. There is no significant gender difference in the median CD4 count of ART-naive HIV-1 seropositive individual with undetectable PVL. The median CD4 count is significantly higher in ART-naive individuals with undetectable PVL compared to ART-naive individual with detectable PVL. Proper understanding of the meaning of undetectable PVL and the significance of immunological status in ART-naive HIV-1 seropositive individual is of paramount importance for the better management of these individuals.

Acknowledgment

The authors would like to thank the Department of Biotechnology under Ministry of Science and Technology, Government of India, for funding the study. (Sanction no. BT/Med/15/Vision-NER/2011, dated 2/11/2011, and Memo No. TU/DBT-NC/MD/MS-P7 and 8/14-15/32, dated 27/08/2015). We also thank all the patients who participated in this study.

Financial support and sponsorship

This study was financially supported by Department of Biotechnology under Ministry of Science and Technology, Government of India.

Conflicts of interest

There are no conflicts of interest.

References

1. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, et al. Plasma viral load and CD4+lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;126:946-54.

2. Odaibo GN, Adewole IF, Olaleye DO. High rate of non-detectable HIV-1 RNA among antiretroviral drug naive HIV positive individuals in Nigeria. Virology (Auckl) 2013;4:35-40.

3. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescent; 2014. Available from: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdol escentGL.pdf. [Last accessed on 2014 Nov 15].

4. Roche Molecular Diagnostics. COBAS [R] TaqMan [R] HIV-1 Test, v2.0 for Use with the High Pure System for in vitro Diagnostic Use; 2013. Available from: http://www.pimeservices.roche.com/eLD/(S (vz2b4ca4kgom1ixbxfzq2vnp))/tw/en/Documents/GetDocument?documentId=318989aa-12f4-e311-98a1-00215a9b0ba8. [Last accessed on 2015 Sep 11].

5. Garcia F, Vidal C, Gatell JM, Miro JM, Soriano A, Pumarola T, et al. Viral load in asymptomatic patients with CD4+ lymphocyte cWounts above 500 x 10(6)/l. AIDS 1997;11:53-7.

6. Fauci AS, Lane HC. Human immunodeficiency virus disease: AIDS and related disorders. In: Fauci AS, Kasper DL, Longo DL, Loscalzo J, Hauser SL, Jameson JL, editors. Harrison's Principles of Internal Medicine. 19th ed. USA: The McGraw-Hill Education; 2015. p. 1215-85.

7. Hunt PW, Hatano H, Sinclair E, Lee TH, Busch MP, Martin JN, et al . HIV-specific CD41 T cells may contribute to viral persistence in HIV controllers. Clin Infect Dis 2011;52:681-7.

8. Okulicz JF, Marconi VC, Landrum ML, Wegner S, Weintrob A, Ganesan A, et al. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US department of defense HIV natural history study. J Infect Dis 2009;200:1714-23.

9. Ingole NA, Kukreja SM, Mehta PR. Role of HIV-1 viral load in initiating antiretroviral therapy. World J AIDS 2011;1:149-54.

10. National AIDS Control Organisation. State HIV Epidemic Fact Sheets, 2014. Available from: http://www.naco.gov.in/upload/2014%20mslns/STATE%20HIV%20EPIDEMIC%20FACT%20SHEET.pdf. [Last accessed on 2015 Aug 27].

11. Joint United Nations Programme on AIDS. Global Summary of AIDS Epidemic; 2014. Available from: http://www.unaids.org/sites/default/files/mediaasset/20150714epicoreen.pdf. [Last accessed on 2015 Aug 13].

12. Pereyra F, Palmer S, Miura T, Block BL, Wiegand A, Rothchild AC, et al. Persistent low-level viremia in HIV-1 elite controllers and relationship to immunologic parameters. J Infect Dis 2009;200:984-90.

13. Church D, Gregson D, Lloyd T, Klein M, Beckthold B, Laupland K, et al. Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for determination of HIV-1 viral loads in a cohort of Canadian patients with diverse HIV subtype infections. J Clin Microbiol 2011;49:118-24.

14. Re MC, Vignoli M, Furlini G, Gibellini D, Colangeli V, Vitone F, et al. Antibodies against full-length tat protein and some low-molecular-weight tat-peptides correlate with low or undetectable viral load in HIV-1 seropositive patients. J Clin Virol 2001;21:81-9.

15. Wateba IN, Patassi AA, Balaka A, Tidjani O. Viral characteristic of HIV infected patients naive of anti-retroviral therapy with CD4+T lymphocytes rate greater than 350 per microliter of blood in Lome Togo. World J AIDS 2013;3:364-6.

16. Manolescu L, Marinescu P. Sex differences in HIV-1 viral load and absolute CD4 cell count in long term survivors HIV-1 infected patients from Giurgiu, Romania. Rev Rom Med Lab 2013;21:218-24.

17. Delmas MC, Jadand C, De Vincenzi I, Deveau C, Persoz A, Sobel A, et al. Gender difference in CD4+cell counts persist after HIV-1 infection. SEROCO study group. AIDS 1997;11:1071-3.

Source Citation

Source Citation   

Gale Document Number: GALE|A529917016