Peripheral neuropathy was
identified in one-in-four children on HIV treatment in rural Mopani District, one of the
poorest and least well-resourced areas in South Africa, Dr Remco Peters
reported today at
19th International AIDS Conference (AIDS 2012) in Washington, DC.
The findings underline the
importance of improving paediatric antiretroviral formulations suitable for use
in sub-Saharan Africa.
In this cross-sectional study
of 182 children, aged from 5 to 15, 86% were receiving an antiretroviral (ART) regimen that
included d4T (stavudine, Zerit).
Among HIV-infected adults, peripheral
neuropathy is common and well recognised. It affects between 30 and 60% of
people with HIV and may be related to HIV infection and/or the drugs used to
treat HIV. Few studies have been able to distinguish between peripheral
neuropathy as a result of HIV itself and neuropathy as a side-effect of ART.
Other contributing factors include vitamin and mineral deficiencies and autoimmune effects.
Peripheral nerves are
responsible for sensation-pain, pressure, heat sensation (sensory nerves)
movement (motor nerves) and automatic bodily functions such as breathing,
heartbeat, sweating and emptying of the stomach (autonomic nerves). Damage to
these nerves is called neuropathy.
In most people with HIV, nerve
damage usually starts in the hands or feet (hence the term 'peripheral' neuropathy), affecting both sides of the body and
involving multiple nerves. It can range from mild numbness or pain to
debilitating pain. Other symptoms include increased sensitivity to touch,
diminished reflexes and weakness. It can severely affect quality of life.
Stavudine (d4T) and
didanosine (ddI, Videx, Videx EC) are two of the anti-HIV drugs known as dideoxynucleoside
reverse transcriptase inhibitors or ‘d-drugs’, which can cause peripheral neuropathy.
The World Health Organization
(WHO), concerned about the side effects of d4T (principally abnormal body fat
loss, or lipoatrophy, and peripheral neuropathy in adults) has urged national
– wherever affordable
– to drop d4T and move to tenofovir-
(Viread) or AZT-based treatment regimens in adults.
The findings of the study
presented today are likely to reinforce calls for access to paediatric formulations
of abacavir (Ziagen) in settings where d4T is the only current alternative. Abacavir
is already available for paediatric use in southern Africa, and is recommended by the World Health Organization as a component of first-line
paediatric treatment, but remains substantially more expensive than stavudine.
A powder version of tenofovir
suitable for use in children aged two to five years is licensed for use in the
United States, but safety studies have not been carried out in children in
sub-Saharan Africa to evaluate any potential risk of kidney toxicity or
decreased bone mineral density. The South African HIV Clinicians Society
has suggested that tenofovir should be used with caution in young children
until further safety data are available.
In June of this year, WHO issued
guidance on the best use of tenofovir in adolescents and children over two
years of age The recommended dose is 8 mg/kg body weight (up to a maximum of 300 mg),
administered once daily using either an oral powder formulation or low-strength
is needed nonetheless since tenofovir in combination with ddI increases the risk of
ddI-related toxicities, including peripheral neuropathy.
Peripheral neuropathy is
diagnosed based on symptoms and is more difficult to diagnose in children. Few
tools exist for clinical screening for peripheral neuropathy in children.
Children may find it difficult to describe their symptoms.
Few data exist on the extent,
symptoms or causes of peripheral neuropathy among HIV-positive children in
sub-Saharan Africa, where d4T is in common use. Among the estimated 2.3 million
HIV-positive children, between 2008 and 2009, approximately 90% were on an ART
regimen containing d4T.
The researchers chose to use
neuropathy symptom score (NSS) and neuropathy disability score (NDS) to screen
for peripheral neuropathy in this cohort of children.
NSS, a subjective assessment
tool, includes a series of questions about location and severity of pain and pain
relief (for example, does sitting help?) in the feet and legs. Each response is
given a score of 0, 1 or 2. Total scores of 3, 5 and 7 indicate mild, moderate and
severe neuropathy, respectively.
The NDS, an objective
assessment tool, looks at ankle reflex (0, 1 or 2), vibration perception (0 or 1),
pin-prick perception (0 or 1) and temperature perception (0 or 1) and scored. A
reflex hammer, cotton swabs, a toothpick and cold water are all that is needed
to carry out the test.
An NSS score equal to or
above 3 or an NDS score equal to or above 2 was used as a definitive diagnosis
of peripheral neuropathy. Dr Remco noted these were conservative cut-off
In total, 96% (174/182) of this cohort
of children, all collecting ART from nurse-managed treatment programmes, completed screening
for peripheral neuropathy. This included a questionnaire, physical exam, NSS
and NDS scores.
The median age was 9.2 years
with median time on ART of two years (2 months to 6.4 years).
Forty-nine children (27%) reported
symptoms related to neuropathy, while 25 children (14%) met the NDS criteria.
Overall, 43 children (25%) were identified as having peripheral neuropathy. Examples of children's descriptions of symptoms included:
- “My feet
are burning, I must take off my shoes in class otherwise I can’t concentrate.”
- “I can’t
sleep at night because of the tingling in my feet; I’m tired during the
Dr Remco noted that, while
the cause of peripheral neuropathy was not addressed in depth, being on ART for
a longer period of time (p=0.06) was a major contributor.
Dr Remco concluded that, in
this region, peripheral neuropathy among children is common and often goes undiagnosed.
Simple and easy to use, the NSS and NDS are valuable tools for assessing peripheral
neuropathy in a resource-poor and skills-limited setting.
The most important lesson
learned is “quite simply, to talk to the child”, he added. In these settings, “We
[healthcare workers] do not talk to the children, we will talk to the mother
or caregiver about the child but never directly to the child.”