Challenges encountered in administering the second dose Nevirapine to the infants born

to HIV positive women in Namakkal PMTCT Project, India.

Vijayakumari JJ, Sara Mini J, Samuel NM; International Conference on AIDS (15th :
2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. ThPeB7034.

Namakkal Govt. Hospital, Namakkal, India

Issues: Administering second dose Nevirapine to the infants poses many challenges like
ignorance, illiteracy, stigma and discrimination, cultural practices and lack of transport
facilities. The mothers are eager to protect their infants from HIV infection but are
ignorant to understand the importance of the second dose Nevirapine. Due to stigma and
discrimination, they tend to avoid visiting the hospital for delivery and thus miss the
second dose. Economical constrains force them to deliver at the nearby sub centers or at
home. Culturally elders decide where the delivery should take place. Description:
Namakkal PMTCT project is funded by the EGPAF. Voluntary counseling and HIV testing is
offered to all antenatal women who visit the Namakkal and Rasipuram Government
hospitals. The seropositive pregnant women are offered antiretroviral prophylaxis with
single dose Nevirapine for the mother and the infant. For the past 6 months, 58 pregnant
women were found to be HIV positive. 8/49 women refused to take medicine and 2/49
prematurely delivered. 39 (79.6%) pregnant women received the first dose of
Nevirapine. 31/37 (83.7%) infants received the second dose of Nevirapine. The infants
who did not receive the second dose were those who delivered at remote subcenters and
homes. The families find it difficult to communicate for lack of facilities and long
distances. Therefore the health care workers are unable to reach the mother infant pairs
within the stipulated time. The mothers bring their infants to the hospital when they are
able to travel and this reveals their ignorance and lack of understanding of the second
dose of Nevirapine. These rural women cannot afford to take a private vehicle to come to
the hospital for delivery. Recommendations: Counselling on the importance of the 2
doses of Nevirapine is to be stressed. Research is needed to provide the second dose to
pregnant women to take home in order that the infant does not miss the dose

Publication Types:

• Meeting Abstracts

Keywords:
 • Counseling
• Female
• HIV Infections
• HIV Seropositivity
• Humans
• India
• Infant
• Nevirapine
• Pregnancy
• Rural Populatio

The Practicalities of Using Nevirapine for PMTCT in Under-Resourced Set

The case of Qaukeni District in the Eastern Cape Province, South Africa
Henry Fomundam, Thabang Mosala, Olive Shisana, Karl Peltzer, Thembiso Pakade, Pelisa Dana

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Implementation of the programmes intended to prevent mother-to-child transmission of HIV/AIDS (PMTCT) is a major challenge, particula
Despite the controversies about Nevirapine (NVP) resistance, safety and efficacy, it is still widely acclaimed and used in most resource-lim
affordable, easy-to-use and practical. This study identifies the gaps in NVP use for PMTCT in a rural setting, where almost 42% of pregnan
healthcare facilities and deliver at home, with the support of traditional birth assistants or family members. As a result, many rural HIV-po
deliver without the opportunity of PMTCT therapy provided by ante-natal clinics.

In response to this problem, an innovative, clinically safe intervention has been designed. This enables HIV-positive pregnant women to s
therapy to both themselves, at the onset of labour, and to their newborn, shortly after birth. The study proposes that the widespread use
greatly improve access to PMTCT services for HIV-positive pregnant women.

The report provides District, Provincial and National PMTCT programme managers with information on the challenges of NVP use in rural c
solution for women with inadequate access to health care facilities.

Contents

Progress and emerging challenges Add to marked items

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Journal Current Infectious
Disease Reports
Publisher Current Medicine
Group LLC
ISSN 1523-3847 (Print)
1534-3146
(Online)
Issue Volume 7, Number
5 / September,
2005
DOI 10.1007/s11908-
005-0014-0
Pages 393-400
Subject Collection Medicine
SpringerLink Date Thursday, May 24,
2007

PDF (352.6 KB) Free Preview

Matthew F. Chersich and Glenda E. Gray1

(1) Perinatal HIV Research Unit, University of the Witwaterstrand, Chris Hani Baragwanath
Hospital, Old Potch Road, PO Berstham, 2013 Soweto, South Africa
Abstract There is a widening gulf between the effectiveness of interventions
for preventing mother-to-child transmission (PMTCT) of HIV in sub-Saharan
Africa and other regions of the world. Compared with long-course, triple
antiretroviral regimens used in Brazil, Europe, and the United States, most
countries in sub-Saharan Africa use a less effective regimen consisting of
single-dose nevirapine (NVP). Furthermore, the documentation of unacceptable
levels of resistance following this regimen makes it prudent to review current
PMTCT strategies. Not only is it necessary to review the use of single-dose NVP
for PMTCT, but efforts to minimize breast milk transmission of HIV should be
enhanced. This review summarizes the programmatic and evidence-based
reasons for adopting a standardized approach to long-course, triple-drug MTCT
prophylaxis in sub-Saharan Africa. Antiretroviral treatment programs in
resource-constrained settings have achieved similar levels of effectiveness as
high-income countries, despite adopting standardized approaches to
antiretroviral treatment. Similarly, in resource-constrained settings with
adequate infrastructure and programmatic capacity, use of standardized, long-
course, triple-drug regimens for MTCT prevention are likely to achieve levels of
effectiveness seen in Brazil, Europe, and the United States.
Glenda E. Gray
Email: gray@pixie.co.za

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Challenges faced by PMTCT programmes

Even where PMTCT services are available, not all women receive the full benefit.
Reasons for HIV positive pregnant women not accessing drugs include:

• Not being offered an HIV test

• Refusing to take an HIV test
• Not returning for follow up visits
• Not adhering to self-administered drugs
HIV tesing is critical because women who do not know they are HIV positive cannot
benefit from interventions. However some women refuse to be tested because they fear
learning that they have a life-threatening condition; because they distrust HIV tests; or
because they do not expect their results to remain confidential, and fear stigma and
discrimination following a positive result.

Some women who test HIV positive do not return to clinics for follow up visits, or fail to
take the drugs they have been given. This can happen because they have had negative
experiences interacting with clinic staff, or because they have been poorly informed
about HIV transmission and how it can be prevented. Some women having tested
negative early in pregnancy can become infected during pregnancy; without returning to
clinics for retesting treatment is not accessed27 . Also, some women choose not to attend
clinics because by doing so they might disclose their HIV positive status. In the words of
a woman from Cote d'Ivoire:

"My husband might see me with the medicines, and he will want to know what they are
for. That way he will find out about my [HIV positive test] result. Even the location
bothers me, because everyone who comes to the clinic knows what goes on [at the
programme]. As soon as a pregnant woman is seen coming here, it's known right away
that she is seropositive."28

One of the major problems in preventing mother-to-child transmission, it has been

argued, is making the provision of ARV drugs the focus of PMTCT efforts. Access to
other services such as counselling, care and treatment services, infant-feeding guidance,
and in particular sexual and reproductive health is ignored as a result. Therefore, it should
not be assumed that the proportion of HIV-positive pregnant women who are receiving
antiretroviral prophylaxis to prevent their child becoming infected – estimated at one-
third in developing countries – are receiving comprehensive PMTCT services.29

To achieve a high success rate, PMTCT programmes must have well-trained, supportive
staff who take great care to ensure confidentiality. They must be backed up by effective
HIV testing and counselling programmes and by good quality HIV/AIDS education,
which is essential to eliminate myths and misunderstandings among pregnant women,
and to counter stigma and discrimination in the wider community. Under these
conditions, antiretroviral drugs have the potential to save many thousands of babies' lives.

The current situation

Since the UNGASS target, PMTCT services have been significantly scaled up. In 2005,
only 15% of HIV-infected pregnant women received preventive drugs – barely making a
dent in the number of infant infections. In 2006 the proportion was 23%,3 and by 2008 an
estimated 45% of pregnant women living with HIV in low- and middle-income countries
received antiretroviral drugs to prevent HIV transmission to their infants.4

Despite this increase, many countries still do not have enough PMTCT services and
existing services are not reaching many of the local women in need.
Availability of PMTCT services

To achieve wide coverage, PMTCT programmes must be integrated into existing public
health systems, with services provided by all antenatal and delivery clinics. So far, only a
few developing countries have achieved this goal.

One reason given for the slow progress is that most health systems are poorly resourced:
clinics are struggling to provide conventional services, let alone new ones. Yet although
some improvements in infrastructure may be required, there is abundant evidence that
PMTCT programmes are feasible even in the poorest parts of the world. 5 These
interventions are cost effective and deserve to be seen as a necessary part of maternal and
child health care. 6 7 Moreover, as researchers have noted:

“Should infrastructural improvements be necessary, the cost of these should be

considered in the wider context of all the potential benefits to other health care areas.
Thus the mobilizing of resources for MTCT prevention programmes should be seen as a
catalyst for improving other areas of maternal and child health, and other areas of
primary HIV prevention.” 8

Several countries in Latin American and the Caribbean – most notably Brazil – have
already succeeded in providing PMTCT services to most pregnant women who attend
clinics. 9 Thailand, too, has provided wide access since 1999. 10

A video about PMTCT in the Democratic Republic of Congo.

In Southern Africa, where HIV is very widespread among pregnant women, Botswana
leads the way. High quality PMTCT services are provided in all of the country’s public
facilities through the Maternal Child Health/Family Planning system, which serves over
95% of pregnant women. 11 Test results from between November 2006 and February
2007 indicate that less than 4% of babies born to HIV positive mothers in Botswana were
infected - a rate comparable with the USA and Western Europe.12

With sufficient effort, other countries could follow these examples.

Efficiency of PMTCT services

Preventing mother-to-child transmission might seem simple: just hand out lots of pills. In
fact there’s much more to it than that. To begin with, the vast majority of women in the
developing world have never been tested for HIV and don’t know whether they’re
infected. This means that effective PMTCT programmes must provide counselling and
testing services to determine which women need assistance.

And even if a clinic offers counselling and testing to every pregnant woman, the reality is
that not all of them accept. Others, having been tested, fail to return to receive their
results. This is just the beginning of a series of steps that leads to the ideal outcome,
which is to reduce the risk of transmission as far as possible. At each step, some women
drop out. By the end, it’s possible that only a minority will remain. The entire process is
illustrated below.

This phenomenon can be seen in data from pilot PMTCT programmes supported by
UNICEF between January 2000 and June 2002. Of more than half a million women who
attended clinics in twelve countries, only 71% received counselling; of those who were
counselled, only 70% took an HIV test; among women who tested HIV positive, only
49% received preventive drugs. Assuming that HIV prevalence among all women was
similar to the rate among those who were tested, fewer than one in four HIV-infected
women who attended a clinic went on to receive the drugs that they needed. 13

Many other studies in very poorly resourced areas have shown that such high drop-out
rates are not unusual. 14 15 16 17 18 However, they have also found that some PMTCT
programmes perform much better than others.

Improving efficiency means looking at nine main issues: accessibility; clinic resources;
testing methods; fear and distrust; disclosure and discrimination; drug effectiveness;
treatment for mothers; feasibility of replacement feeding; and male visits to antenatal
clinics.

Accessibility

Poor women in the developing world have many responsibilities. Besides caring for their
children they are expected to work hard preparing food, fetching water or tending crops.
Many live a long way from their nearest health facility and have little access to transport.
It is therefore hardly surprising that a third of the world’s pregnant women don’t attend
antenatal clinics. 19
Many other women visit clinics only once during pregnancy, and nearly two-thirds give
birth unattended by a skilled health worker. 20 This already greatly reduces the number
that can be reached by PMTCT programmes. The problem is compounded if women have
to make follow-up visits to receive counselling, drugs or other services.

One study in Zambia found that a third of those given the drug never ingested it

To increase attendance, clinics should aim to be as accessible as possible. Improvements

might include providing travel services or changing opening hours. For example, one
programme in rural India boosted attendance by setting up a Saturday clinic. 21

Women who are HIV positive should be encouraged to give birth at a clinic.
Nevertheless, to attain high coverage, PMTCT programmes also need to reach those who
deliver at home. One way to achieve this is to give a nevirapine pill to each HIV-positive
woman in advance – perhaps even at the time of diagnosis – to be kept at home and taken
at the start of labour. Yet although giving the drug in advance can increase the number of
women who receive it, there is no guarantee that every pill will be swallowed. 22 One
study in Zambia found that a third of those given the drug never ingested it. 23 Scientists
in Uganda found better results, but only among a community used to taking part in
scientific research. 24

Moreover, to be fully effective, medication needs to reach newborn babies as well as their
mothers. Infant doses are given in syrup form and are usually available only to women
who give birth in clinics. 25 Some programmes have however succeeded in dispensing the
syrup in advance, inside sealed oral syringes, so it can be given after home births. 26 27

PMTCT programmes can increase acceptance of self-administered drugs by working with

traditional birth attendants, who attend the majority of home deliveries. With sufficient
training, traditional midwives might also be able to provide other services such as HIV
education, testing and counselling, and advice on infant feeding. 28

Clinic resources

Shortages of HIV test kits, preventive drugs and other supplies can limit the efficiency of
PMTCT programmes. It is therefore important to have reliable supply chains that are
integrated into the systems serving maternal and child health clinics.

Staff shortages and motivational issues can also be very significant, especially when it
comes to counselling, which takes a long time to do well. As a UNICEF report explains:

“PMTCT programs are being introduced into health care systems that in many cases are
already seriously under-staffed due to lack of resources, outflows of trained providers to
private institutions or to other countries that offer higher salaries, and, possibly, AIDS-
related mortality. PMTCT interventions – although designed to be part of routine services
– create significant additional work for staff already discouraged by long-standing
problems such as low pay and inadequate medical supplies.” 29
Ultimately, the best solution is to recruit more health workers. In the shorter term, better
training, greater support and motivation can improve the efficiency of existing staff.
Boosts to morale may include psychosocial support, improved availability of supplies,
training on universal precautions, and post-exposure prophylaxis (PEP), which helps to
prevent health workers becoming infected with HIV. 30

Another proven remedy is the recruitment of lay counsellors, either paid or unpaid, to
help provide counselling. With a few weeks training and ongoing supervision, lay
counsellors can give a good quality service and lighten the workloads of full-time
professionals. 31 32 33

Issues of using nevirapine for PMTCT

A major concern with using nevirapine for PMTCT is that NNRTI resistance mutations
are commonly observed in both mothers and infants after single-dose nevirapine and may
compromise the response to future NNRTI-containing regimens.

Persistence of nevirapine exposure during the postpartum period after

administration for PMTCT of HIV

This study aimed to determine nevirapine (NVP) plasma levels during the postpartum
period after a single intrapartum nevirapine dose for the prevention of mother-to-child
transmission. It was found that significant nevirapine concentrations remained for up to
20 days in the study participants. We could conclude that to ensure coverage is
maintained until nevirapine concentrations fall to nonsuppressive levels, 1 month of
additional antiretroviral treatment after delivery should be considered to prevent the
emergence of resistant viruses.

For further information please refer to Persistence of nevirapine exposure during the
postpartum period after intrapartum single-dose nevirapine in addition to zidovudine
prophylaxis for the prevention of mother-to-child transmission of HIV-1. [pubmed.gov]
Exposure to nevirapine and subsequent responses to nevirapine based
therapy

Whether there were clinically significant consequences in mothers who are subsequently
treated with a nevirapine-containing regimen was previously unknown. This study found
that women who received intrapartum nevirapine were less likely to have virologic
suppression after six months of postpartum treatment with a nevirapine-containing
regimen. The study suggests the need for strategies to maximize the benefits of both
antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral
therapy for mothers. Since this study, PHPT and others have performed research to find
ways for women to benefit from single dose nevirapine and avoid the selection of
resistance mutations. PHPT-4 and P1032 are examples of such studies

Triple-drug treatment during pregnancy reduces risk of nevirapine resistance

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Kelly Safreed-Harmon, Thursday, August 13, 2009
A small Kenyan study has contributed new information to the complex body of evidence
that is helping researchers identify new strategies for the prevention of mother-to-child
transmission of HIV (PMTCT). The study suggests that a widely used prophylactic
antiretroviral regimen, AZT (zidovudine, Retrovir) plus a single dose of nevirapine
(Viramune), may be more likely to cause nevirapine resistance than a three-drug regimen
being evaluated for its potential to reduce HIV transmission during breastfeeding.

The resistance findings came out of a randomised PMTCT study that had the primary
objective of comparing HIV levels in the breast milk of two groups of HIV-positive
women with baseline CD4 cell counts of 200 to 500 cells/ mm3.

One group was prescribed 300 mg of ZDV twice daily for the last six weeks of pregnancy
plus a single 200-mg dose of nevirapine during labour. (Newborns also received a single
dose of nevirapine [2mg/kg].)
The other group was prescribed a twice-daily regimen of 300 mg AZT, 200 mg
nevirapine, and 150 mg 3TC (lamivudine, Epivir) for the last six weeks of pregnancy and
first six months post-partum.

The resistance substudy was based on analyses of plasma samples collected three months
after treatment ended – three months postpartum for the AZT/single dose nevirapine
group (N=23) and nine months postpartum for the nevirapine/AZT/3TC group (N=17).
Twenty-seven samples were suitable for viral load testing: sixteen from the AZT/single
dose nevirapine group, and eleven from the nevirapine/AZT/3TC group.

Three-quarters of women (12/16) in the AZT/single dose nevirapine group had either the
K103N mutation or the Y181C mutation or both, compared to 18% (2/18) in the triple
treatment arm group, a statistically significant difference (p = 0.006). These rates
translated into 13.5 times higher odds of resistance in the AZT/single dose nevirapine
group, according to univariate logistic regression analysis (p=0.007). Further analyses led
investigators to conclude that viral load level, CD4 count, and viral subtype were not
confounding factors.

Nevirapine is one of the most effective antiretrovirals for preventing mother-to-child

transmission of HIV, but a major challenge associated with the use of nevirapine is that it
lingers in the body longer than other antiretrovirals after the discontinuation of treatment,
resulting in a high risk of resistance. (Without additional drugs helping to suppress viral
replication, HIV can more easily mutate to become resistant to the single drug that it
encounters.) Nevirapine resistance is signaled by the emergence of the K103N and
Y181C mutations, which diminish over time in some people but persist in others. In
short, women who use nevirapine-containing PMTCT regimens run the risk of
developing K103N- and Y181C-mediated nevirapine resistance, and thus limiting their
future treatment options.

The Kenyan study underscored this concern by demonstrating that resistance persisted at
six months and twelve months post-treatment in a large proportion of cases, according to
allele-specific PCR testing. Two of the five women with K103N mutations still had those
mutations at twelve months post-treatment. Y181C mutations persisted at twelve months
post-treatment in eight of nine women in the AZT/single dose nevirapine group, and also
persisted at six months post-treatment in one of two women in the triple drug treatment
group.

The authors propose that the two regimens they investigated may cause different degrees
of risk for resistance because nevirapine/AZT/3TC lowers HIV viral load levels much
more than AZT/single dose nevirapine. “As a result, the levels of replicating virus during
the period when drug levels wane immediately after treatment cessation is lower with
[nevirapine/AZT/3TC],” they state.

A further consequence of using the triple-drug regimen, they add, is that 3TC stays in the
body for longer than AZT, reducing the amount of time after treatment cessation when
NVP remains as the only active drug.
The strategy of using a 3TC “tail” at the end of a period of treatment with the AZT/single
dose nevirapine regimen to reduce nevirapine resistance has been explored by other
researchers, and there is clear evidence that doing so reduces the risk of resistance. The
authors note that “it is unknown whether the addition of a ‘tail’ concurrent with treatment
cessation of AZT/single dose nevirapine would make the prevalence of resistance in the
two regimens studied here more similar.”

Even so, the study findings are notable for what they contribute to ongoing efforts to
improve PMTCT regimens. A key question is whether regimens taken during
breastfeeding further reduce postpartum HIV transmission; if so, understanding the
benefits and drawbacks of those regimens is crucial.

“The data presented here should be considered as a benefit of [antiretroviral prophylaxis

during breastfeeding] when balancing the safety, efficacy, and feasibility of different
strategies currently being tested to reduce breastfeeding transmission,” the authors
conclude.

The World Health Organization is currently undertaking an evidence review that will
guide revisions to its PMTCT recommendations, with one outcome expected to be an
updated approach to reducing HIV transmission through breastfeeding. The new
recommendations are scheduled for December 2009 publication.

References

Lehman DA et al. Lower risk of resistance after short-course HAART compared with
zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child
transmission. J Acquir Immune Defic Syndr 51: 522–529, 2009.
How will AZT and nevirapine use for MTCT affect future treatment? Two studies
provide clues
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Theo Smart, Friday, November 14, 2003

Two studies in the November 1st edition of the Journal of Acquired Immune Deficiency
Syndromes address the issue of drug resistance in women taking drug prophylaxis to
prevent mother to child transmission of HIV. One found an increased risk of transmission
in mothers infected with phenotypic AZT-resistant virus. The other reported that
efavirenz-based regimens were as effective in patients exposed to short courses of
nevirapine as in patients with no prior nevirapine exposure.

Since ACTG 076, the first study of AZT in pregnant women, dramatic progress in the
prevention of mother to child transmission (MTCT) of HIV has been achieved.
According to an editorial accompanying the two reports, use of anti-HIV drugs by
pregnant women has reduced HIV transmission by more than 70%. Today in North
America and Western Europe, some studies report as few as 2 percent of children born to
HIV-positive women turn out to be HIV-infected because of antiretroviral prophylaxis
and other interventions.

However, the drugs usually employed - AZT, 3TC or nevirapine monotherapy or dual
nucleoside analogues - are not what anyone would characterise as optimal therapy for the
mother herself. Some experts have voiced concerns that these short courses of mono or
dual therapy might lead to resistance, eventually reversing the great strides made
reducing MTCT and even lead to increasing transmission of resistant HIV to infants.
Furthermore, some worry that the development of resistance might limit any benefit that
the mother or infant could one day receive from triple drug therapy, particularly in the
developing world where only a limited number of regimens are available.

The first paper reported findings from one of the oldest ongoing perinatal HIV studies in
the United States, the Women and Infants Transmission Study (WITS). This study
evaluated the effect of phenotypic AZT-resistance on MTCT was evaluated in 74 AZT-
treated mothers enrolled in the study up until September 1994. These women had
moderately advanced disease, with a median CD4 cell count of 271 and a median viral
load of 39,811 copies per mL. Factors independently associated with AZT resistance at
delivery included previous use of AZT (before pregnancy), high viral loads, and low CD4
cell counts.

Sixteen of the women (22%) passed HIV onto their infants. After adjustment for other
variables known to increase the risk of transmission (such as duration of membrane
rupture at delivery), decreasing susceptibility to AZT was shown to be associated with an
increased risk of transmission. These findings build on a prior WITS study that identified
an increased risk of transmission in women with genotypic AZT-resistant virus (virus
known to contain mutations associated with AZT resistance).

There also have been reports that transient mutations associated with nevirapine-
resistance have been observed in15–19% of women 6 weeks after receipt of a single-dose
(200mg) of nevirapine administered during delivery to prevent MTCT of HIV. Even
though 12-month follow-up of these women revealed no detectable mutant virus in most
cases, the rapid emergence of resistance has led to concerns over the increasingly
widespread use of nevirapine to prevent MTCT in resource-limited settings.

Since no data are currently available from international MTCT programs on the effect of
single-dose nevirapine on future treatment outcomes, authors of the second JAIDS study
looked at patients in an American cohort who had received a short course of nevirapine
(<28 days) as part of combination therapy that was stopped due to rash or other toxicity
(nevirapine resistance mutations have also been observed in such patients); who were
then later treated with a regimen containing efavirenz, another nonnucleoside reverse
transcriptase inhibitor that shares a similar resistance profile.

The patients were drawn from the HIV Outpatient Study (HOPS) which prospectively
gathers treatment data on about 3000 patients from nine urban US clinics. Responses to
efavirenz in the nevirapine pretreated patients were compared with those of patients with
no prior exposure. Treatment success was defined as achieving viral loads below 400
copies per mL at 1–3, 4–8, and 10–14 months after starting efavirenz-based combination
regimens.

Responses to efavirenz-containing regimens were compared between twenty-six patients

with less than 28 days of nevirapine exposure and 495 patients with no prior reported
nevirapine exposure. The demographic profiles were similar for both groups. The mean
interval between stopping NVP and initiation of an EFV-containing regimen was 518
days.

There were no significant differences in the proportion with treatment success among
those cases with prior NVP exposure of less than 28 days and those with no prior NVP
exposure: 42% of both cases and controls achieved undetectable viral loads (less than 400
RNA copies per mL) at 1–3 months after starting efavirenz; 42% of cases and 56% of
controls had undetectable viral loads at 4–8 months; and 46% of cases and 53% of
controls had undetectable viral loads at 10–14 months.

The authors note that “while these US findings are not directly applicable to the maternal
single-dose nevirapine regimens used in international PMTCT programs, they do suggest
that prior exposure to nevirapine may not necessarily result in higher rates of treatment
failure for women later are treated with efavirenz-containing regimens.”

The accompanying editorial notes that follow-up studies are planned and/or underway in
Uganda, Botswana, South Africa, and Thailand to assess whether women exposed to
single-dose nevirapine are at increased risk of treatment failure when placed on
combination antiretroviral regimens containing nonnucleoside reverse transcriptase
inhibitors and whether viral subtype influences treatment outcome.

Additionally, the editorial’s authors note that “it will also be important to carefully
monitor whether there is a heightened risk of adverse events for African women who
receive non-nucleoside reverse transcriptase inhibitors as part of combination treatment
regimens. Enhanced risk of severe nevirapine-associated rash hypersensitivity and
hepatic toxicity has been reported among women as well as among individuals with
higher CD4 cell counts, and there have been several case reports of significant nevirapine
toxicity among black HIV-infected pregnant women receiving chronic nevirapine
therapy.” Meanwhile, it is well known that efavirenz use should be avoided in pregnant
women or women at risk of becoming pregnant because of the risk of birth defects. “If
high rates of nevirapine toxicity with chronic dosing were to be observed among African
women, given the concerns of teratogenicity with the use of efavirenz among women of
childbearing age,” they conclude that “careful reconsideration would need to be given as
to the optimal first-line antiretroviral therapy for women in resource-limited settings.”

References

Bauer GR et al. Zidovudine resistance phenotype and risk of perinatal HIV-1

transmission in zidovudine monotherapy–treated mothers with moderately advanced
disease. J Acquir Immune Defic Syndr 34: 312–319. 2003.

Fowler, MG; Mofenson L; and McConnell M. The Interface of perinatal HIV prevention,
antiretroviral drug resistance, and antiretroviral treatment? What do we really know? J
Acquir Immune Defic Syndr 34: 308-310, 2003

Fowler, MG et al. Does prior short-course nevirapine reduce the effectiveness of

subsequent combination treatment with efavirenz? J Acquir Immune Defic Syndr 34:
348-350, 2003.

Mother-to-Child Transmission: How Will AZT and Nevirapine Use for MTCT Affect
Future Treatment?

Two Studies Provide Clues

By Theo Smart
Winter 2003/2004

This article is part of The Body PRO's archive. Because it contains information that may
no longer be accurate, this article should only be
considered a historical document.

Two studies in the November 1, 2003 edition of the Journal

of Acquired Immune Deficiency Syndromes [JAIDS] address
the issue of drug resistance in women taking antiretroviral
prophylaxis to prevent mother-to-child transmission [MTCT]
of HIV. One found an increased risk of transmission in
mothers infected with phenotypic AZT [zidovudine,
Retrovir]-resistant virus. The other reported that efavirenz
[Sustiva]-based regimens were as effective in women
exposed to short courses of nevirapine [Viramune] as in those with no prior nevirapine
exposure.

Since ACTG 076, the first study of AZT in pregnant women, dramatic progress in the
prevention of MTCT of HIV has been achieved. According to an editorial accompanying the two
reports, use of anti-HIV drugs by pregnant women has reduced HIV transmission by more
than 70%. Today in North America and Western Europe, some studies report as few as 2% of
children born to HIV-positive women turn out to be HIV-infected because of antiretroviral
prophylaxis and other interventions.

However, the drugs usually employed -- AZT, 3TC [lamivudine, Epivir], or nevirapine
monotherapy, or dual nucleoside analogues [NRTIs] -- are not what anyone would
characterize as optimal therapy for the mother herself. Some experts have voiced concerns
that these short courses of mono- or dual therapy might lead to resistance, eventually
reversing the great strides made in reducing MTCT, and even lead to increasing transmission
of resistant HIV to infants. Furthermore, some worry that the development of resistance might
limit any benefit that the mother or infant could one day receive from triple-drug therapy,
particularly in the developing world where only a limited number of regimens are available.