Triple Antiretroviral Therapy Effectively Eliminates HIV Transmission From Mother to Child

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Juan Pablo Rodríguez Miranda

Distrital Francisco José de Caldas University. Faculty of Environment and Natural Resources. Bogota D.C. Colombia.

[Ofﬁcial Representative of Journal in Latin America, Colombia and the Caribbean]

3

Dr. Rajendra B. Kakde,

Professor , University Department of Pharmaceutical Sciences, RTM Napur University, Nagpur, MH, India, (Former Research Scientist Cadila, Lupin, Glenmark R& D).

4

Dr. Abdellah ECH-CHAHAD, Ph.D

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Dr. El Sayed El Habbasha, Professor,

National Research Centre El Tahrir st., Dokki, Cairo, Egypt

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Dafeng Chu

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7

Dr. Ahmed A. Abd-Rabou,

Researcher (PhD holder), Medical Biochemistry and Cancer Biology, Medical Research Division, National Research Center (NRC), Egypt. (Permanent; 2008 up to date).

Executive Editors[A & R]

1

Dr. Fazlul Huq,

Head Cancer Research Group, School of Medical Sciences, Faculty of Medicine, Australia.

2 Dr.Pavel Mokrejs,

Thomas Bata University,The Czech Republic, Europe.

3 Dr. Adli Abdallah Hanna, National Research Centre, Egypt.

4 Dr. P.Y.Shirodkar, University of Mumbai,India.

5 Dr. M. Al-Anber,_{Mu´tah University, Jordan.}

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16/02/18 17.31 Editorial PharmTech

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7 University of Pitesti, Romania.

8 Dr. Nurfina Aznam,_{University Negeri Yogyakarta, Indonesia.}

9 Dr. Tomasz Borowski,_{Centre Lab of Chem.Tech.,Poland.} 10 Dr. Mas Rosemal Hakim bin Mas Haris,

School of Chemical Sciences Universiti Sains Penang, Malaysia.

11 Dr.Alamdar Ashnagar, Pasteur Institute of Iran.

12 Dr. Abdulkareem Ismaiel Abdulraheem, College of Health Sc.,PAAET, Kuwait.

13 Dr. Ji-Tai Li,_{Hebei University, China.} 14 Dr.Abdalla Shalaby,

Zigzag University,Egypt

15 Dr. Georgia Koliopoulou,

University of Athens, Athens, Greece.

16 Dr. A. A. Mottahedi , IROST,Iran

17 Dr. Gwendoline Ee Cheng Lian,_{University PutraMalaysia, Malaysia.}

18 Dr. J.V.Manwar,_{GSPS.IOP, M.S.India.} 19 Dr.Miss Swastika Ganguly,

Birla Insti.of Tech.,India.

20 Prof. Dr. Sbirna Simona-Liana, University of Craiova, Romania.

21 Dr Carolyn Coulter,

University of Otago, New Zealand.

22 Dr. Konstantinos M. Kasiotis,_{B P Institute, Laboratory of Pesticides Toxicology, Athens, 14561, Greece.} 23 Dr. Arun HS Kumar,

University College Cork,Ireland.

24 Associate editors: Dr. M.Z. Kumbhare,M.S.India.Dr. S.R.Ninawe,M.S.India.

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INDEX Page-1.

S.N.(Page

Numbers) Title of Paper and Names of Authors

(01-09)

Association Between Caffeine with Cyp450 1a2 And Il-6 Levels in Acehnese Who Suffer from Coronary Heart Disease

Azhari Gani, Aznan Lelo, Muhammad Yamin, Effendy de lux Putra, Harun Al Rasyid Damanik

Abstract Full Text PDF Full Text XML

(10-18)

Characterization of lytic phage Staphylococcus aureusfrom dairy farm cows in Indonesia

Priyanto Dwi Nugroho, Sri Budiarti, Iman Rusmana

(19-28)

Impacts of bcl2 t(14,18) chromosomal translocation, and EBV lmp-1 genes on Non-Hodgkin lymphomas

Mahdi M. R. Al-Sahlawi

(29-37)

Is Air Pollution A Leading Risk Factor For Stroke: A Review

Anjana Surendran, Shanmuga Sundaram Rajagopal, Krishnaveni Kandasamy, Sudha Muthusamy, Sambathkumar Ramanathan

(38-46)

The Effects of Caesalpinia sappan L. Extract Granule to Antioxidant Activity In Blood Serum of Wistar Rat (Rattus norvegicus) With Excessive Iron Condition

Ratu Saﬁtri, Nining Ratningsih, Ani Melani Maskoen, Prima Nanda Fauziah, Ramdan Panigoro

(47-53)

(4)

16/02/18 17.31 Page # 1

Page 2 of 5 http://www.sphinxsai.com/2016/ph_vol9_no11/ph01.htm

Akhmad Yogi Pramatirta, Bremmy Laksono, Prima Nanda Fauziah, Anita Deborah Anwar, Soﬁe Rifayani Krisnadi, Debbie S. Retnoningrum, AniMelani Maskoen, Erlina Widiarsih

(54-57)

Identiﬁcation of Risk Factors caused neonatal Sepsis of Premature Neonatusin Adam Malik General Hospital Center

Yettrie Bess Congencya Simarmata, Urip Harahap, Guslihan Dasa Djipta

(58-63)

HSP70 Gene Expression in Serum and Tissue of Rat Cochlear (Rattus norvegicus) Due to Noise Exposure and Heat

R. YusaHerwanto, SyafruddinIlyas, Rr. Suzy Indharty

(64-67)

Seaweed as a source of carbohydrates in the feed of milkﬁsh(Chanoschanos Forsskal)

Siti Aslamyah, Yusri Karim, Badraeni, Akbar Marzuki Tahya

(68-71)

Triple antiretroviral therapy effectively eliminates HIV transmission from mother to child

SN Lumbanraja, SR Sanusi

(72-77)

Potential Bengle(Zingiber cassumunar Roxb.) Rhizomes for Sunscreen and Antioxidant Compounds

Endang Dwi Wulansari, Subagus Wahyuono, Marchaban, Sitarina Widyarini

(78-83)

Comparison Of Biological Characteristic And Osteogenic Differentiation Between Bone Marrow And Adipose Mesenchymal Stem Cell In Various Age Group

William Chandra, Ismail Hadisoebroto Dilogo

(84-93)

In vitro Antibacterial activity of Plants extracts against Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans Streptococcus mutanus, Isolated from Periodontitis Patients in Babylon province, Iraq

Nada Khazal Kadhim Hindi

(94-102)

Evaluation of the anxiolytic effect of rosemary in mice

Entisar J. Al Mukhtar, Selman M. Selman, Hamid Naji

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(103-109)

Synthesis and Antioxidant Assay of C-2-Ethoxyphenylcalix[4]resorcinarene

SantiNur Handayani, Jumina, Mustofa, Respati Tri Swasono

(110-120)

Antimicrobials Activity, Antioxidants Activity and Analysis of Active Extract Chemical Compounds Content of Moringa (Moringa oleifera Lam.) Leaf

Masfria, Ginda Haro, Nerdy, Vriezka Mierza, Henny Sri Wahyuni, Yade M Permata

(121-127)

Comparison of Antibacterial Activity of Ethanolic Extract from Immature and Mature Nipa Leaves (Nypa fruticans, Wurmb) against Staphylococcus aureus and Escherichia coli

Panal Sitorus

(128-132)

Study of Microbial Diversity of Rosa Centifolia

Nisha Kumari, Biji A. Varghese, T. Rashmi, Pramita Ghosh, Abhishek Suman, Anjuvan Singh

(133-141)

Effect of Black Cumin Seeds (Nigella Sativa) Ethanol Extracts on Blood Pressure, Proteinuria, and ET-1 Level in Preeclampsia Mice Model I

Wayan Agung Indrawan, Siti Chandra WB, Bambang Rahardjo, Edi Mustofa, Wisnu Barlianto, Agus Sulistyono, Handono Kalim, Edy Widjajanto

(142-150)

Effect of the Experimental Infection withToxoplasma gondii on some Biochemical aspects and Histological Changes for the Liver and Spleen in Female Rats

Halla Abdul–HadiCHabuk, Haidar Kamil Zaidan Al-Saadi and Ahmed Khudhair Al-Hamairy

(151-160)

A study on Antidermatophytic Potential of Ocimum tenuiﬂorum Essential Oil and Chemical Composition Evaluation

Vishnu Sharma, Anima Sharma and Ruchi Seth

(161-177)

Potential Modulator Role of Chlorella Vulgaris and Spirulina Platensis On Monosodium Glutamate Oxidative Stress, Genotoxicity, Apoptotic Gene Expression and Histopathological Alterations

Aida I El makawy, Sekena H Abdel-Aziem, Faten M Ibrahim,Haﬁza A Sharaf, Omaima M Abd-Elmoneim, Ahmed M Darwish

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16/02/18 17.31 Page # 1

Page 4 of 5 http://www.sphinxsai.com/2016/ph_vol9_no11/ph01.htm

(178-186)

Sami,A. Metwally; Kh.I.Hashish; Sawsan, S. Sayed; Lobna, S. Taha

(187-202)

Hypoglycemic, hypolipidemic and antioxidant activities of Allium porrumleaves extract in streptozotocin-induced diabetic rats

Samy M. Mohamed, Gehad A. Abdel Jaleel, Heba M.I. Abdallah, Samir A.E. Bashandy, Adel B. Salama, Ahlam H. mahmoud

(203-209)

Detection of Nucleoprotein gene of Human Metapneumovirus and Chemokines & Histopathology study

Fadyia Mahdi Muslim Alameedy

(210-215)

Study The Properties For Unsaturated Polyester (UP) With Addition Glass Fiber (GF) And Polyvinylchloride (PVC) Powder By Ultrasonic Technique

Mohammed H. Al-Maamori, Rusul M.Abd Alradha

(216-228)

Antibacterial, Anti-virulence factors of Pipercubeba extracts on Escherichia coli and staphylococcus saprophyticus isolated from patient with urinary tract infection

Shahad Abed Al Rdheha Ali, Wejdan R. Taj Al-daan, Anwar Al Saffar

(229-236)

Evaluation natural cloning of azole- resistantgenes CDR1,CDR2,MDR and ERG11 between clinical and soil isolates of Candida albicans based on gene expression

Zaidan Khlaif Imran and Zahra Abd Al-Karrem

(237-245)

The effect of water stress and magnetic water in the production of trignolline in callus of Fenugreek (Trigonella foenumgraecum L.)plant

Basheer Abdulhamza Alalwani, Elaf Abdulameer Alrubaie

(246-251)

The Effects of Yasmin on the Histology and Histochemistry of Liver and Kidney in Rabbits

Fakhir M. Alzubaidy, Rafah S. Almuttairi and Aymen A. Bash

(252-259)

Seroepidemiological aspects for Toxoplasma gondii infection in women of Qadisiyah province, Iraq.

Hadeel S. Hadi, Raad A. Kadhim, Raheem T. O. Al-Mammori

(7)

(260-266) _{Intisar Hadi AL-Yasari, Thekra Abdul-A’ali Al-ka’abi; Ali H. Al-Saadi}

(267-273)

Effect of ß lactam Antibiotics with Aminoglycosides on Multidrug Resistance Staphylococcus aureus

Mohammed O. Hamad, Wadhah A. Abbas, B. A. Almayahi

(274-279)

Optical Characterization of SnO2and SnO2:CoDeposited by Spray Pyrolysis Technique

Nahida B. Hasan, Amani Ali Sekeb

(280-288)

Evaluation of the Activities of Health Promotion and Communicable Disease Staff for the Control of Cholera Epidemic in Al-Hilla City

Haqi I. Mansoor, Amean A. Yasir

Next 1 2

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Triple antiretroviral therapy effectively eliminates HIV

transmission from mother to child

SN Lumbanraja

1

, SR Sanusi

2

1

_{Department of Obstetrics and Gynaecology Medical Faculty Universitas Sumatera}

Utara, Indonesia

2

_{Faculty of Public Health Universitas Sumatera Utara, Indonesia}

Abstract :

_{Introduction: HIV transmissions can be reduced to a very low value by managing}

patient accurately. Every centers have modified their own standardized regimen for antiretroviral therapy.

Aim: To determine the HIV status after standardized triple antiretroviral therapy adapted in Haji Adam Malik Hospital.

Methods: This is an cohort-analytic study conducted in Haji Adam Malik hospital. Medical records of HIV-positive mother who delivered at Haji Adam Malik Hospital, starting in 2009-2014 were collected. They were all being given standardized antiretroviral therapy adapted in Haji Adam Malik Hospital. Diagnosis of HIV in children under the age of 18 months were done by PCR (Polymerase Chain Reaction). If the child has been aged ≥ 18 months, the method of diagnosis is Rapid Test.

Results: Of the 60 children examined, 11 children were aged <18 months and require PCR tests, while 49 others children were tested using rapid test. Of all children who tested PCR, no virus were detected. Similarly, in the examination of 49 children with a rapid test, all showed negative results.

Conclusion: The triple antiretroviral was effectively prevented the HIV transmission from mother to child.

Keywords : HIV, antiretroviral, transmission, pregnancy, fetal

Introduction

UNAIDS estimates there are 35.9 to 44.3 million people living with HIV in worldwide. This number is growing about 15,000 patients per day.1 The number of patients in South Asia and Southeast Asia are estimated at around 7.4 million in 2005. In Indonesia, HIV infection incidence has been increasing since 1999. In 2002, Data of Ministry of Health of Indonesia showed 90,000 and 130,000 cases of HIV infection. The amount is certainly still very far from the real number.2

Almost half of the 42 million people living with HIV are women of reproductive age. In addition, more than 2 million HIV-infected are pregnant womena and up to 90% of them are in developing countries, especially in Africa. The highest incidence of HIV infection are in East and Southern Africa.3

Transmission from mother to child can occur through intrauterine, intrapartum and during breastfeeding. The incidence of children with HIV was 330,000 in 2011, doubling of incidence in 2003, but 24% lower than the peak of 570,000 cases in 2009. PMTCT (Prevention of Mother to Child Transmission), can reduce transmission up to 90% using antiretroviral therapy (ART) for pregnant women and newborn child.4

International Journal of

Pharm

Tech Research

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Highly effective antiretroviral therapy (HAART) during pregnancy can reduce the HIV-1 MTCT rate to as low as 1% -2%, even in developing countries, and is now recommended for prevention of mother to child transmission (PMTCT) by the World Health Organization.Highly effective antiretroviral therapy (HAART) during pregnancy can reduce the HIV-1 MTCT rate to as low as 1%–2%, even in developing countries, and is now recommended for prevention of MTCT (PMTCT) by the World Health Organization.5

Haji Adam Malik Hospital is the center for HIV-positive pregnant women who were referred from various hospitals in Sumatera region. Treatment for HIV-positive pregnant women need a comprehensive collaboration between fetomaternal division with HIV unit that established since 2012. The goal for this program is to ensure patient received antiretroviral therapy, give education about the disease (omit breastfeeding, prefer caesarean section), prevent HIV transmission, and take back infant for follow up after the age of 18 months. The main problems encountered were patients came to hospital during active stage of labor. Mostly delivery occurred before the schedule date, which brought the need of emergency cesarean section. Then, after birth, only about 30% of these babies were coming regularly until the age of 18 months for follow up.

Methods

This is an cohort-analytic study conducted in H. Adam Malik hospital. Medical records of HIV-positive mother who delivered at Haji Adam Malik Hospital, starting in 2009-2014 were collected.

In this study, will be investigated how the child's HIV status after a standardized antiretroviral therapy Haji Adam Malik Hospital. There are four drug regimen given to pregnant women. The first regimen: tenofovir, lamivudine, nevirapine with contraindications for patients with kidney disorders. The second regimen: tenofovir, lamivudine, efavirenz, preferably in patients with tuberculosis or central nervous system disorders. Three regimens: zidovudine, lamivudine, and nevirapine with contraindications anemia (Hb <10 g/dL) and CD4+ above 250/mm3. Four regimens: zidovudine, lamivudine, and efavirenz. The first and second regimens given 2 times daily while the third and fourth regimen given 4 times daily. Cotrimoxazole is given to patients with CD4+ less than 200/mm3. Newborns are given zidovudine to 6 weeks.

Diagnosis of HIV in children under the age of 18 months were done by PCR (Polymerase Chain Reaction). PCR was conducted in the laboratory Prodia Medan because Haji Adam Malik Hospital not have facilities for PCR. If the child has been aged ≥ 18 months, the method of diagnosis is rapid test.

Results

There were 60 HIV-positive data that eligible for this study. Author collected blood samples from all infants from HIV-positive mothers in their visit to the hospital for follow up. The rest who did not show up were phoned and being asked to come for follow up. All the babies are not breastfed. Of the 60 infants, only three were born by spontaneous vaginal delivery. All babies born with normal weight (> 2500 g) and average 3164.5 ± 238.8 g.

Table 1. Characteristics of newborns from HIV-positive mothers

Newborn characteristics n %

Gender

Male 29 48.3

Female 31 51.7

Mode of delivery

Vaginal 3 0.05

Abdominal 57 0.95

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SN Lumbanraja et al/International Journal of PharmTech Research, 2016,9(11): 68-71. 70

Table 2. HIV test results of newborns

HIV test n %

PCR in children <18 months (n=11)

Virus detected 0 0

No virus detected 11 100

Rapid test in children ≥18 months (n=49)

Positive 0 0

Negative 49 100

Discussion

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue reverse transcriptase inhibitor (NRTI) that has excellent efficacy and tolerability profiles.6Baroncelli et al. (2009) did not find any obstetrics and fetal outcomes in pregnant women who received tenofovir.7Nevirapine is a HIV-1 specific non-nucleoside reverse transcriptase inhibitor that binds directly to the viral reverse transcriptase of HIV-1 to block polymerase activity by causing disruption of the enzymes catalytic site.8Lamivudine is a nucleoside reverse transcriptase inhibitor that is widely used for the treatment of HIV-1 infection in combination with other antiretrovirals. It is a highly effective agent that can be dosed once or twice daily due to its long intracellular half-life.9Efavirenz is a non-nucleoside reverse transcriptase inhibitor that in most treatment guidelines is recommended to be taken

combined with two nucleoside analogue reverse transcriptase inhibitors.10After GS903 study showed that in 144

weeks comparison between tenofovir vs stavudine (plus lamivudin and efavirenz, 71 of 86 (83%) patients originally randomized to efavirenz plus tenofovir and lamivudine had VL of <400 copies/mL and 69/86 (80%) had a VL of <50 copies/mL, the regimen was being switched from stavudine to tenofovir (plus efavirenz and lamivudine) also showed maintained virological suppression and continued CD4 cell increases over 144 weeks.11Zidovudine is a nucleoside transcriptase inhibitor that compete with the endogenous nucleotides at the catalytic, i.e., substrate-binding, site of RT and are incorporated into the elongating proviral deoxyribonucleic acid (DNA) strand.12

The four line regimens are the same regimen as adapted bycurrent WHO guidelines recommendation: tenofovir + 3TC + nevirapine, tenofovir/FTC + nevirapine, tenofovir + 3TC + efavirenz, and tenofovir/FTC/efavirenz. The first regimen: tenofovir, lamivudine, nevirapine with contraindications for patients with kidney disorders. However, tenofovir + 3TC + nevirapine regimen showed high rates of failure in the latest study. Lapadula et al. have reported that regimens consisting of tenofovir, emtricitabine, and nevirapine are associated with a risk of early virologic failure in antiretroviral-naive, HIV-infected patients.The second regimen: tenofovir, lamivudine, efavirenz, preferably in patients with tuberculosis or central nervous system disorders. Three regimens: zidovudine, lamivudine, and nevirapine with contraindications anemia (Hb <10 g/dL) and CD4+ above 250/mm3. Four regimens: zidovudine, lamivudine, and efavirenz. The first and second regimens given 2 times daily while the third and fourth regimen given 4 times daily. Cotrimoxazole is given to patients with CD4+ less than 200/mm3. Newborns are given zidovudine to 6 weeks.14

The current WHO recommended regimen is as follows: where the pregnant woman does not yet need to start ART for therapeutic reasons, she should start Zidovudine (AZT) from 28 weeks or as soon as possible

thereafter, be provided with single-dose Nevirapine (NVP) when entering labour, and be given AZT + 3TC for

one week following delivery. Meanwhile, whether the mother was on the above or standard ART, the child

should be given single dose NVP immediately after delivery and daily AZT until one week old.14

In this study, both two groups of 11 children were aged <18 months with PCR and 49 children with rapid test showed negative HIV status.This rate is similar to less than 2% the developed world where PMTCT

have access to comprehensive testing, and counseling services and treatment.15Although inadequate continuum

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Conclusion

The triple antiretroviral was effectively prevented the HIV transmission from mother to child.

References

1. Drake AL, Wagner A, Richardson B & Stewart GJ. Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis. PloS 2014; 1-14.

2. WHO. Global HIV/AIDS response: epidemic update and health sector progress towards universal access. WHO, 2011.

3. UNAIDS. Treatment 2015. UNAIDS: WHO, 2015.

4. UNAIDS. Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mother alive. UNAIDS, 2011.

5. Chasela CS, Hudgens MG, Jamieson DJ, et al. Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med 2010;362:2271-81.

6. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vsstavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004;292:191-201.

7. Baroncelli S, Tamburrini E, Ravizza M, et al.. Antiretroviral treatment in pregnancy: a six-year perspective on recent trends in prescription patterns, viral load suppression, and pregnancy outcomes. AIDS Patient Care STDS2009;23:513-20.

8. Harris M, Montaner JS (2000) Clinical uses of non-nucleoside reverse transcriptase inhibitors. Rev Med Virol 10: 217–229

9. P. D. Ziakas, P. Karsaliakos, and E. Mylonakis. Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance. Haematologica, vol. 94, no. 7, pp. 998–1005, 2009.

10. Vrouenraets SM1, Wit FW, van Tongeren J, Lange JM. Efavirenz: a review. Expert

OpinPharmacother. 2007 Apr;8(6):851-71.

11. Madruga JR, Cassetti I, Suleiman JM, et al. The safety and efficacy of switching stavudine to tenofovir DF in combination with lamivudine and efavirenz in HIV-1-infected patients: three-year follow-up after switching therapy. HIV Clin Trials.2007;8:381–90.

12. Wooding AM. Antiviral efficacy of nine nucleoside reverse transciptase inhibitor against feline immunodeficiency virus in feline peripheral blood mononuclear cells. Available from: https://edoc.ub.uni-muenchen.de/18251/1/Wooding_Anita.pdf

13. Lapadula G, Costarelli S, Quiros-Roldan E, et al. Risk of early virological failure of once-daily tenofovir-emtricitabine plus twice-daily nevirapine in antiretroviral therapy-naive HIV-infected patients. Clin Infect Dis 2008;46:1127-9.

14. WHO. Global update on HIV treatment 2013: result, impact, and opportunities. WHO, 2013: 1-126. 15. Cooper E, Charurat M, Mofenson L, et al: Combination antiretroviral strategies for the treatment of

pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. Acquir Immune DeficSyndr. 2002, 29: 484-494.

16. WHO, UNAIDS and UNICEF: Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Progress report, 2005, 2006, 2007, 2008, 2009, 2010, WHO, UNAIDS, UNICEF. 2009, Available at http://data.unaids.org/pub/Report/2009/20090930/tuapr_2009_en.pdf