Indian Journal of Pharmacology Medknow Publications on behalf of Indian Pharmacological Society ISSN: 0253-7613 EISSN: 1998-3751 Vol. 43, Num. 2, 2011, pp. 207-209

Indian Journal of Pharmacology, Vol. 43, No. 2, March-April, 2011, pp. 207-209

Short Communication

Safety of single-dose nevirapine for prevention of vertical transmission of human immunodeficiency virus infection

Mangala Bhaskar Murthy¹, Bhaskar Krishnamurthy²

¹ Department of Pharmacology, Government Medical College, Miraj, India
² Department of Obstetrics and Gynecology, Government Medical College, Miraj, India

Correspondence Address: Mangala Bhaskar Murthy, Department of Pharmacology, Government Medical College, Miraj , India, mangala.bhaskar@gmail.com

Date of Submission: 03-Sep-2010
Date of Decision: 10-Dec-2010
Date of Acceptance: 16-Jan-2011

Code Number: ph11054

DOI: 10.4103/0253-7613.77372

Abstract

Keywords: Nevirapine, prevention of mother to child transmission of HIV, vertical transmission

Introduction

The global HIV pandemic has continued unabated in the 21 ^st century. There are around 2.7 million HIV-positive people in India and currently almost half of all new HIV infections are reported in women. National statistics reveal the fact that 1,89,000 pregnancies are borne by HIV-positive women in India annually. Of these, 19-36% are without intervention and would transmit the infection to their offspring. ^[1] As it is known that almost 75% of vertical transmission occurs during the peripartum period, ^[1] systemic viricidal drugs given peripartum to mother and child could effectively interrupt vertical transmission. Out of the multiple regimes that have been tested for prevention of vertical transmission of HIV, single-dose nevirapine has emerged as one of the most convenient, cheap, and efficacious regimes. ^[2] Prevention of parent to child transmission of HIV program (PPTCT) is an important component of the Government of India′s AIDS control program, which has adopted the single-dose nevirapine regime to keep a check on vertical transmission of HIV. In India, PPTCT services are being offered in more than 500 centers ^[3] distributed over high HIV prevalence areas and our hospital is one of them.

The HIVNET012 trials conducted in Uganda which confirmed the efficacy of the single-dose nevirapine regime in preventing vertical transmission of HIV were plagued by controversies soon after the release of its results in 2004. Press reports state that the severe adverse reactions like serious hepatotoxicity and rashes were concealed and only efficacy data were accurately published. Although these controversies were cleared later, the safety of nevirapine was questioned as planned studies to evaluate the same were few.

Thus, the primary purpose of our study was to evaluate the safety of single-dose nevirapine used to prevent vertical transmission of HIV. Secondary objectives were to estimate the prevalence of HIV in patients attending the antenatal clinic in our hospital, to estimate the proportion of HIV positive mothers eligible to receive single-dose nevirapine, and to identify the contraindications, if any to single-dose nevirapine for prevention of vertical transmission in HIV-positive patients.

Materials and Methods

This study was carried out in the inpatient department of obstetrics and gynecology at Padmabhushan Vasantdada Patil Government Hospital, Sangli, over a duration of one year adhering to the principles of the declaration of Helsinki.

All women attending antenatal clinic, who consented to participate in the study, were offered pretest counseling to undergo a rapid HIV diagnostic test according to National AIDS Control Organization (NACO) guidelines. The rapid diagnostic test kit which detects antibodies to three different HIV antigens was used one after the other to confirm diagnosis of HIV status. All three tests being positive confirmed HIV positivity, any two positive tests were reported as HIV indeterminate and were sent for confirmation through western blot test or PCR. Any two negative tests were labeled as HIV negative. Results of the diagnostic test were revealed during post-test counseling and those women whose HIV serostatus was known to be positive after voluntary testing were given the option to receive single-dose nevirapine provided there were no contraindications for the administration of nevirapine like delayed presentation in the second stage of labor, severe pregnancy-induced hypertension, or any other severe medical disorder as per baseline clinical and laboratory examinations. HIV-positive patients already on highly active antiretroviral therapy (HAART) did not require administration of nevirapine as HAART itself is efficient in preventing vertical transmission and no additional benefit is conferred by addition of single-dose nevirapine in these patients. ^[4]

Mode of delivery according to NACO guidelines depends on obstetric indications. Although cesarean section reduces transmission rate, it has to be coupled with administration of top feeds to the infant. Most of our patients belonging to low economic status opted to breast feed their children. Hence, single-dose nevirapine was given to reduce maternal viral load without interfering with the mode of delivery in these patients.

Drug regimen included administration of one oral dose of 200 mg of nevirapine tablet to mother at the onset of labor (first stage) and one oral dose of nevirapine syrup 2 mg/kg to the newborn within 72 h of birth. Both mother and child were followed up for 1 week postpartum to note the occurrence of any adverse drug reactions. The study monitored adverse events which included all the events reported by or observed in the patients receiving single-dose nevirapine. Objective adverse reactions, like rash and hepatitis, were monitored by clinical examination and lab investigations if prompted by clinical examination, while subjective symptoms like rash, nausea, vomiting, headache, and fatigue were monitored by questioning the patient. Any new adverse reaction, suspected to be due to nevirapine could be noted in a separate column of monitor chart. In consultation with a pediatrician follow up of newborn was also done to note any adverse reaction in the child receiving single-dose nevirapine, by daily clinical examination.

Results

Out of 4079 patients admitted to the labor ward during the study period, 93 (2.28%) patients were HIV positive [Figure - 1]. Among these HIV-positive patients in the labor ward, only 73 (78.49%) were eligible to receive nevirapine and the other 20 (21.51%) patients could not receive nevirapine as a result of some contraindication its use. The most common contraindication for administration of nevirapine was late presentation which was defined as presentation in the second stage of labor in 12 patients followed by severe pregnancy-induced hypertension in 5 patients and jaundice in 3 patients [Table - 1]. Out of the 73 patients who received nevirapine, none had any severe adverse reaction [Table - 2]. Eight patients reported nausea, six patients complained of headache, and only one patient reported to have vomiting. No patient reported rash or jaundice.

Discussion

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral drug. It noncompetitively inhibits the reverse transcriptase enzyme and slows down HIV replication. It has been used as a part of highly active anti-retroviral therapy (HAART) for long, and recently employed singly for prevention of vertical transmission of HIV. The efficacy of single-dose nevirapine in preventing vertical transmission of HIV has been proved beyond doubt. ^[5] Several studies had questioned the safety of nevirapine. ^{[6],[7],[8],[9]} The most frequent adverse drug reactions associated with nevirapine when used as a component for HAART include rash, life-threatening Steven Jhonson′s syndrome, and elevated hepatic transaminases. ^[7] Severe and fatal hepatitis has been reported with nevirapine use and this may be more common in pregnant women. ^[8],[9] Other reported adverse effects include fever, headache, somnolence, nausea, and fatigue. In the present study, none of the above-mentioned adverse effects were noted except nausea, vomiting, and headache which were tolerable and self-limiting and did not require any specialized treatment. The newborn, also followed up for 1 week postpartum did not show any significant adverse reaction to the prophylactic dose of nevirapine. Hence, the current study suggests the safety of single-dose nevirapine used for prevention of vertical transmission of HIV. Thus, while counseling, over emphasis should not be given to rash aspect of nevirapine, rather the beneficial effect on cutting down vertical transmission may be highlighted to allay the anxiety of HIV-positive mothers.

One issue not addressed in this study is the development of resistance mutations in virions in the patients exposed to single-dose nevirapine. Since nevirapine is a long acting drug, the selection of resistant mutants leading to viriological failure in future when the same patients are administered NNRTI class of drugs or during consecutive pregnancies is a matter of concern. Further, many authors agree that mutations conferring resistance to nevirapine do occur after exposure to single-dose nevirapine but these mutations tend to fade away over a duration of 6-12 months. ^[10] The rate of viriological failure and an increased risk of transmission in future pregnancies thus may not be of serious concern. Some studies have proposed the co-administration of other drugs like zidovudine and lamivudine along with nevirapine to prevent the development of resistance. However, addition of these drugs would not only increase the risk of exposure to the other drugs thereby decreasing the safety but also increases the cost of therapy and make the regime more complicated and less acceptable to the patients.

The efficacy of nevirapine in reducing the rate of vertical transmission could not be assessed in the present study as the rapid testing kits available for testing HIV status of mother could not be used to test HIV status of child after delivery due to interference with passive antibodies from mother. Due to protocol constraints such a study could not be conducted.

Currently, the PPTCT program covers only 10% of HIV-positive pregnant mothers. ^[1] The lack of awareness about available regimes and safety concerns hinder the administration of single-dose nevirapine to the needy expectant mothers by many practitioners. Reassurance of safety of single-dose nevirapine and reduced concerns about resistance will make the nevirapine regime an inexpensive and acceptable method to prevent vertical transmission of HIV, thereby paving the way to complete prevention of vertical transmission of HIV in future.

References

Copyright 2011 - Indian Journal of Pharmacology

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