Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested case-control study in a resource poor setting

Kerina Duri, Felicity Z Gumbo, Knut I Kristiansen, Nyaradzi E Kurewa, Munyaradzi P Mapingure, Simbarashe Rusakaniko, Mike Z Chirenje, Fredrik Muller, Babill Stray-Pedersen, Kerina Duri, Felicity Z Gumbo, Knut I Kristiansen, Nyaradzi E Kurewa, Munyaradzi P Mapingure, Simbarashe Rusakaniko, Mike Z Chirenje, Fredrik Muller, Babill Stray-Pedersen

Abstract

Objective: To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on in utero and intra-partum/postpartum transmissions in a breastfeeding population.

Design: A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants.

Methods: A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control).

Results: From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrollment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during in utero and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log10 viral load was associated with a 178 cells/mm(3) and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034.

Conclusion: Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load.

Figures

Figure 1
Figure 1
Summary of the sampling of the 32 transmitters and 32 non-transmitters.

References

    1. UNAIDS. Epidemiology Fact Sheet on HIV and AIDS, Zimbabwe, UNAIDS Geneva. 2008.
    1. Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Lutalo T, Nalugoda F, Sewankambo N, Kiduggavu M, Wawer M, Gray R. Mortality of HIV-1 infected and uninfected children of HIV-1 infected and uninfected mothers in rural Uganda. J Acquir Immun Defic Syndrome. 2006;41(Suppl 4):504–508. doi: 10.1097/01.qai.0000188122.15493.0a.
    1. Mbizvo EM, Msuya SE, Stray-Pedersen B, Sundby J, Chirenje MZ, Hussain A. HIV sero-prevalence and its association with the other reproductive tract infections in asymptomatic women in Harare, Zimbabwe. International Journal of STD and AIDS. 2001;12:524–531. doi: 10.1258/0956462011923624.
    1. Gregson S, Gonese E, Hallet TB, Taruberekera N, Hargrove JW, Lopman B, Corbett EL, Dorrington R, Dube S, Dehne K, Mugurungi O. HIV decline due to reduction in risky sex? Evidence from a comprehensive epidemiological review. Int J Epidemiol. 2010. in press .
    1. Kourtis AP, Bulterys M, Nesheim SR Lee FK. Understanding the timing of HIV transmission from mother to infant. JAMA. 2001;285:709–712. doi: 10.1001/jama.285.6.709.
    1. Zijenah LS, Moulton LH, Iliff P Nathoo K, Munjoma MW, Mutasa K, Malaba L, Zvandasara P, Ward BJ, Humphrey J. ZVITAMBO Study Group. Timing of mother to child transmission of HIV-1 and infant mortality in the first 6 months of Life in Harare, Zimbabwe. Acquir Immun Defic Syndrome. 2004;18:273–280.
    1. Arvold ND, Ngo-gian-Huong N, McIntosh K, Suraseranivong V, Warachit B, Piyaworawong S, Changchit T, Lallemant M, Jourdain G. Perinatal HIV Prevention Trial (PHPT-1), Thailand. Maternal HIV-1 DNA load and mother to child transmission. AIDS patient Care and STDs. 2007;21(Suppl 9):638–643. doi: 10.1089/apc.2006.0169.
    1. Katzenstein DA, Mbizvo M, Zijenah L, Gittens T, Munjoma M, Hill D, Madzime S, Maldonado Y. Serum level of maternal Human Immunodeficiency Virus (HIV) RNA, infant mortality and vertical transmission of HIV in Zimbabwe. JID. 1999;179:1382–1387. doi: 10.1086/314767.
    1. Ilif PJ, Piwoz EG, Tavengwa NV, Zunguza CD, Marinda ET, Nathoo KJ, Moulton LH, Ward BJ, Humphrey JH. ZVITAMBO study group. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS. 2005;19(Supp l7):699–708. doi: 10.1097/01.aids.0000166093.16446.c9.
    1. Gregson S, Zhuwau T, Anderson RM, Chandiwana SK. Is there evidence for behaviour change in response to AIDS in rural Zimbabwe? Social Science & Medicine. 1998;46:321–330.
    1. Moyo W, Mbizvo MT. Desire for a future pregnancy among women in Zimbabwe in relation to their self-perceived risk of HIV infection, child mortality, and spontaneous abortion. AIDS and Behavior. 2004;8(Suppl 1):9–16. doi: 10.1023/B:AIBE.0000017521.26426.9d.
    1. Lee S, Wong K. The use of total lymphocyte count (TLC) as an independent criterion for initiating HAART in resource-poor countries. J of Infection. 2005;50(1):66–67. doi: 10.1016/j.jinf.2003.11.011.
    1. WHO. Scaling up antiretroviral therapy in resource-limited settings: Guidelines for a public health approach. 2002.
    1. Bryson YJ, Luzuriaga K, Sullivan JL, Wara DW. Proposed definitions' for in utero versus intrapartum transmission of HIV-1. N Eng J Med. 1992;327:1246–1247. doi: 10.1056/NEJM199210223271718.
    1. Cao Y, Krogstad P, Korber BT, Koup RA, Muldoon M, Macken C, Song JL, Jin Z, Zhao JQ, Clapp S, Chen IS, Ho DD, Ammann AJ. Maternal HIV-1 viral load and vertical transmission of infection. Nature Medicine. 1997;3(Suppl 5):549–552. doi: 10.1038/nm0597-549.
    1. O' Shea S, Newell ML, Dunn DT, Garcia-Roudriguez MC, Bates I, Mullen J, Rostron T, Corbett K, Aiyer S, Butler K, Smith R, Banatvala JE. Maternal viral load, CD4 cell count and vertical transmission. Journal of medical virology. 1998;54:113–117. doi: 10.1002/(SICI)1096-9071(199802)54:2<113::AID-JMV8>;2-9.
    1. Fang G, Burger H, Grimson R, Tropper P, Nachman S, Mayers D, Weislow O, Moore R, Reyelt C, Hutcheon N, Baker D, Weiser B. Maternal plasma human immunodeficiency virus type 1 RNA level: A determinant and projected threshold for mother to child transmission. Proc Natl Acad of Sci of the USA. 1995;92:12100–12104. doi: 10.1073/pnas.92.26.12100.
    1. Jourdain G, Mary JY, Coeur SL, Ngo-Giang-Huong N, Yuthavisuthi P, Limtrakul A, Traisathit P, McIntosh K, Lallemant M. Perinatal HIV Prevention Trial Group, Thailand. Risk factors for in utero or intra-partum mother to child transmission of Human Immunodeficiency Virus type in Thailand. J Infect Dis. 2007;196:1629–1636. doi: 10.1086/522009.
    1. Fawzi W, Msamanga G, Renjifo B, Spiegelman D, Urassa E, Hashemi L, Antelman G, Essex M, Hunter D. Predictors of intrauterine and intra-partum transmission of HIV-1 among Tanzanian women. AIDS. 2001;15:1157–1165. doi: 10.1097/00002030-200106150-00011.
    1. Magder LS, Mofenson L, Paul ME, Zorrilla CD, Blattner WA, Tuomala RE, LaRussa P, Landesman S, Rich KC. Risk factors for in utero and intra-partum transmission of HIV. J Acquir Immun Defic Syndrome. 2005;38(Suppl 1):87–95. doi: 10.1097/00126334-200501010-00016.
    1. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Babies transmission study group. N Engl J Med. 1999;341(Suppl 6):394–402. doi: 10.1056/NEJM199908053410602.
    1. Garcia-Bujalance S, Ruiz G, De Guevara CL, Pena JM, Bates I, Vazquez JJ, Gutierrez A. Quantitation of Human Immunodeficiency Virus type 1 in cervico-vaginal secretions in pregnant women and relationship between viral loads in the genital tract and blood. Eur J Clin Microbiol Infect Dis. 2004;23(Suppl 2):111–115. doi: 10.1007/s10096-003-1058-4.
    1. Mayaux MJ, Blanche S, Rouzioux C, Le Chenadec J, Chambrin V, Firtion G, Allemon MC. Maternal factors associated with perinatal HIV-1 transmission, The French cohort Study, 7 years of follow-up observation. J Acquir Immun Defic Syndrome. 1995;8:188–194.
    1. Mayaux MJ, Dussaix E, Isopet J, Rekacewicz C, Mandelbrot L, Ciraru-Vigneron N, Allemon VC, Katlama C, Delfraissy JF, Puel J. Maternal Virus load during pregnancy and mother to child transmission of Human Immunodeficiency Virus type 1: The French Perinatal Cohort Studies. J Infect Dis. 1997;175:172–175.
    1. Gottesman BS, Grosman Z, Lorber M, Levi I, Shitrit P, Mileguir F, Gottesman G, Chower MY. Measurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral load. J Med Virol. 2004;73:167–171. doi: 10.1002/jmv.20071.
    1. Jasseron C, Mandelbrot L, Tubiana R, Teglas JP, Faye A, Dollfus C, Le Chenadec J, Rouzioux C, Blanche S, Warszawski J. ANRS French Perinatal Cohort. Prevention of mother to child HIV transmission: similar access for Sub Saharan African immigrants and for French women. AIDS. 2008;22(Suppl 12):1503–1511. doi: 10.1097/QAD.0b013e3283065b8c.
    1. Goulder PJ, Watkins DI. HIV and SIV CTL escape implication for vaccine design. Nat Rev Immunol. 2004;4:630–640. doi: 10.1038/nri1417.
    1. Bailey JR, Williams TM, Siliciano RF, Blankson JN. Maintenance of viral suppression in HIV-1 infected HLA- B*57+ elite suppressors despite CTL escape mutation. J Exp Med. 2006;203(Suppl 5):1357–1369. doi: 10.1084/jem.20052319.
    1. Goepfert PA, Lumm W, Farmer P, Matthews P, Prendergast A, Carlson JM, Deedeyn CA Tang J, Kaslow RA, Bansal A, Yusim K, Heckerman D, Mulenga J, Allen S, Goulder PJR, Hunter E. Transmission of HIV-1 Gag immune escape mutation is associated with reduced viral load in linked recipients. J Exp Med. 2008;205(Suppl 5):1009–1017. doi: 10.1084/jem.20072457.
    1. Chase AJ, Yang H, Zhang H, Blankson JN, Siliciano RF. Preservation of FoxP3+ regulatory T cells in the peripheral blood of Human Immunodeficiency Virus Type-1 infected Elite suppressors correlates with low CD4+ T cell activation. J Virol. 2008;82(Suppl 17):8307–8315. doi: 10.1128/JVI.00520-08.
    1. Guevara H, Johnston E, Zijenah L, Tobaiwa O, Mason P, Contag C, Mahomed K, Hendry M, Katzenstein D. Prenatal Transmission of Subtype C HIV-1 in Zimbabwe: HIV-1 RNA and DNA in Maternal and Cord Blood. JAIDS. 2000;25(Suppl 5):390–397.
    1. Schumacher W, Frick E, Kauselmann M, Maier-Hoyle V, van der Vliet R, Babiel R. Fully automated quantification of Human Immunodeficiency Virus (HIV) type 1 RNA in human plasma by the COBAS AmpliPrep/COBAS TaqMan system. J Clin Virol. 2007;38(Suppl 4):304–312. doi: 10.1016/j.jcv.2006.12.022.
    1. Michael NL, Herman SA, Kwok S, Dreyer K, Wang J, Christopherson C, Spadoro JP, Young KK, Polonis V, McCutchan FE, Carr J, Mascola JR, Jagodzinski LL, Robb ML. Development of calibrated viral load standards for group M subtypes of human immunodeficiency virus type 1 and performance of an improved Amplicor HIV-1 MONITOR test with isolates of diverse subtypes. J Clin Micro. 1999;37:2557–2563.
    1. Zijenah LS, Humphrey J, Nathoo K, Malaba L, Zvandasara P, Mahomva A, Iliff P, Mbizvo MT. Evaluation of the Prototype Roche DNA Amplification Kit Incorporating the new SK145 and SKCC1B primers in detection of Human Immunodeficiency Virus type 1 DNA in Zimbabwe. J Clin Microbiol. 1999;37(Suppl 11):3569–3571.
    1. Gumbo FZ, Kurewa NE, Kandawasvika GQ, Duri K, Mapingure MP, Munjoma MW, Pazvakavambwa IE, Rusakaniko S, Chirenje MZ, Stray-Pedersen B. Rising mother-to-child transmission in a resource-limited breastfeeding population. Trop Doct. 2010;40:70–73. doi: 10.1258/td.2009.090167.
    1. Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A, Ndinya-Achola J, Bwayo J, Onyango FE, Hughes J, Kreiss J. Effect of breastfeeding and formula feeding on transmission of HIV-1: A randomized clinical trial. JAMA. 2000;283:1167–1174. doi: 10.1001/jama.283.9.1167.
    1. WHO Report, 2010. Exclusive breastfeeding.
    1. Piwoz EG, Humprey JH, Mutasa K, Moulton LH, Iliff PJ. Effects of baby sex on mother to child transmission of HIV-1 according to timing of infection in Zimbabwe. AIDS. 2006;20(Suppl 15):1981–1983. doi: 10.1097/01.aids.0000247123.04703.6e.
    1. Kuhn L, Steketee RW, Abrams EJ, Lambert G, Bamji M, Schoenbaum E, Farley J, Nesheim SR, Palumbo P, Simonds RJ, Thea DM. Distinct risk factors for intrauterine and intrapartum human immunodeficiency virus transmission and consequences for disease progression in infected children. Perinatal AIDS Collaborative Transmission Study. J Infect Dis. 1999;179:52–58. doi: 10.1086/314551.
    1. Isom JB, Gordy PD, Selner JC, Brown LJ, Willis M. Immuno-suppression and Infection. N Eng J Med. 1964;12(Suppl 271):1068–1069.
    1. Mlisan K, Auld SC, Grobler A, van Loggerenberg F, Williamson C, Iriogbe I, Sobieszczyk ME, Abdool Karim SS. CAPRISA Acute Infection Study Team. Anaemia in acute HIV-1 subtype C infection. PLos One. 2008;3(Suppl 2):e1626. doi: 10.1371/journal.pone.0001626. 1-5.
    1. Ernster VL. Nested case-control studies. Prev Med. 1994;23(5):587–590. doi: 10.1006/pmed.1994.1093.

Source: PubMed

3
Subscribe