Advances in Infectious Diseases, 2011, 1, 15-19
doi:10.4236/aid.2011.12002 Published Online December 2011 (http://www.SciRP.org/journal/aid)
15
Melanonychia in Patients Infected with Human
Immunodeficiency Virus Original Communication
Parvaneh Ehsanzadeh-Cheemeh1, Richard M. Grimes2, Paul Rowan3, Yu-Jing Huang3, E. James Essien1,
Stanley T. Lewis4
1The Institute of Community Health, College of Pharmacy, University of Houston, Houston, USA; 2The University of Texas Health
Science Center at Houston Medical School, Department of Internal Medicine, Houston, USA; 3The University of Texas Health Sci-
ence Center at Houston, School of Public Health, Houston, USA; 4TaiMed Biologics, Inc., Houston, USA.
Received September 17th, 2011; revised October 19th, 2011; accepted October 31st, 2011.
ABSTRACT
Study Purposes. This study examined whether melanonychia was more prevalent in 1) HIV positive individuals com-
pared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin
pigmentation. Procedures. 267 HIV positive and 273 HIV negative patients were examined for presence or absence of
melanonychia and level of skin pigmentation using the Fitzgerald scale. Pharmacy records were examined for deter-
mining exposure to zidovudine or stavudine. Chi square, odds ratios and logistic regression were used to examine the
study questions Main Findings. Melanonychia appeared in 49.1% of 267 HIV positive an d 21.8% of 273 HIV negative
subjects. Adjusting for skin pigmentation, HIV positives were 4.1 times more likely to have melanonychia than HIV
negatives. Melanonychia was present in 54% of those receiving zidovudine and in 42% of those receiving stavudine
(OR = 2.73, p = 0.05). In a multivariate model in HIV positives which included skin type, prescription of zidovudine
and/or Stavudine, only dark skin (OR = 14.62, p < 0.001) an d zidovudine (OR = 2.65, p < 0.03) were significant. Prin-
cipal Conclusions. HIV infected persons are prone to melanonychia. This is more frequent in darker skinned persons
and is enhanced in those exposed to zidovudine.
Keywords: Zidovudine, St avudine, Melanonychia, HIV/AIDS, Skin Pigmentation
1. Introduction
Antiretroviral therapy (ART) changed HIV infection from
being a death sentence to a manageable chronic disease.
However, in order for the drugs to maintain their effect-
tiveness, patients must rigorously adhere to their drug
regimens. However, patients often fail to adhere to these
medications. Non-adherence has been attributed to a num-
ber of reasons including patients’ not believing in the
efficacy of ART, lack of social support, irregular clinic
visits, drug abuse, alcohol addiction, psychiatric disease
(especially depression), young age, low literacy and me-
dication side effects [1]. Therefore, potential events that
may cause adherence problems need to be anticipated and
dealt with prior to their occurrence. One problem that has
been shown to cause poor adherence in a variety of set-
tings is concern over the negative changes in physical
appearances that are perceived to be associated with ART.
This has been noted in the United States [2-5], Poland [6],
Brazil [7], Italy [8], and Germany [9]. HIV infected persons
think that appearance changes stigmatize them [10].
A readily visible and frequently occurring change in
appearance of HIV infected persons is the darkening of
the fingernails and toenails [11-14]. This is called mela-
nonychia, a condition that is characterized by longitude-
nal hyper pigmented lines in the nails. Pictures of this
condition can be found on the internet [15]. The increase
in nail pigmentation is caused by amplified pigment pro-
duction by melanocytes, which is due to activation of
nail matrix melanocytes. The mechanism of nail mela-
nocytes activation is not fully known but it is believed to
be partly due to over expression of α-melanocyte-stimu-
lating hormone and adrenocorticotropic hormone activity
as well as ultraviolet light. Melanonychia usually reflects
the presence of a benign lesion within the matrix caused
by a melanocytic nevus, simple lentigo, or increased ac-
tivation of benign melanocytes [16-18]. However, it can
also represent a number of different pathologic condi-
tions including bacterial or fungal infections, melanoma
and other cancers [19]. It is also associated with certain

Melanonychia in Patients Infected with Human Immunodeficiency Virus Original Communication
16
medical procedures including chemotherapy and the use
of certain medications [20,21].
Melanonychia is reported to be more prevalent in
dark-skinned individuals such as persons of African ori-
gin, Hispanics, and Asians [21]. Also, melanonychia has
been associated with the use of zidovudine, a commonly
used anti-HIV drug which is a thymidine analog from the
nucleoside reverse transcriptase inhibitor class of drugs
[22-25]. There is one other commonly used thymidine
analog, nucleoside reverse transcriptase inhibitor which
is called stavudine. No studies were found that investi-
gated whether stavudine was associated with melanony-
chia. So, it is not clear whether the presence of melano-
nychia in HIV infected person is due to skin tone, HIV
infection itself, or to taking zidovudine and/or stavudine
or the interaction of any or all of these factors. Therefore,
a study was conducted to evaluate the prevalence of me-
lanonychia in: 1) HIV infected individuals as compared
to infected individuals who were not HIV-infected; 2) HIV
infected individuals who were exposed to zidovudine
and/or stavudine compared to those who were not, and 3)
persons with various levels of skin pigmentation.
2. Methods
After approval was obtained from the Committee for the
Protection of Humans Subjects of The University of Texas
Health Science Center, (the institutional review board),
267 HIV positive patients were examined to collect in-
formation on presence or absence of melanonychia, skin
pigmentation, and exposure to zidovudine or stavudine.
Information on presence or absence of melanonychia and
skin pigmentation was collected from 273 HIV-negative
volunteers of similar age and gender who were used for
comparison in the study. The HIV negative subjects were
being seen for other medical conditions at the same center.
Both groups were examined using a standardized ex-
amination protocol, whereby the attending clinician as-
sessed the presence or absence of melanonychia by the
examining all twenty nail beds. Skin type was determined
by physical inspection and was classified using the Fitz-
patrick Classification Scale [26]. The scale ranks the dark-
ness of skin on a one to six scale with six being the score
assigned to those with the most pigmented skin. In order
to have a sufficient sample size in each of the skin type
groups, the patients were combined into three groups for
analysis purposes. Those with a Fitzgerald score of 1 and
2 were analyzed as one group, those with scores of 3 and
4 in a second group and those with score of 5 and 6 in the
third group.
Demographics, HIV status and skin type were also ex-
amined to determine the relative frequency of each in pa-
tients with and without melanonychia. A logistic regres-
sion was used to determine likelihood of melanonychia
being dependent upon the predictors of interest: HIV status,
skin coloration type, and whether the patient was exposed
to stavudine or zidovudine. Because some of the patients
had received both of the drugs during different times, an
interaction term for patients receiving both of these me-
dications was also included to see if there was an addi-
tive effect. Another logistic regression model was devel-
oped to determine the likelihood of melanonychia asso-
ciated with skin color for HIV positive participants only.
3. Results
Table 1 reports the demographic characteristics and skin
types of the group with HIV infection and the group that
was HIV free. The two groups were remarkably similar
with regard to race, gender and skin tones. Table 2 illus-
trates the demographic characteristics of patients with and
without melanonychia. There were no statistically signi-
ficant differences with regard to gender or age. There were
differences across race/ethnicity. Melanonychia was found
in 156 of 275 (56.7%) of African-Americans and in 30 of
155 (19.4%) Hispanics. In contrast it was found in only 5
of 110 (4.5%) Caucasians. Persons with skin types 5 and
6 were far more likely to have melanonychia (104 out of
242 or 57.9%) than those with skin types 3 and 4 (44 out
of 206 or 21.4%). Only five out of 92 (5.4%) of those
with skin types 1 and 2 had melanonychia. Persons with
HIV infection were more likely to have melanonychia
(131 out of 267 or 49.1%) than those who were not in-
fected with HIV (60 out of 273 or 21.8%).
Table 3 presents the number and percent of these pa-
tients with HIV infection who were prescribed stavudine,
zidovudine, both drugs and neither of the drugs. Melano-
nychia was found in 39 out of 72 (54%) of patients who
had exposure to zidovudine while it occurred in 24 of 58
Table 1. Demographic and skin type characteristics of HIV
positive and HIV negative subjects.
Total = 540 HIV Positive
N = 267
HIV Negative
N = 273 P value
Age (Mean) 40yrs 40yrs 0.92
Race
White 51 59 0.50
African-American 143 132 0.50
Hispanic 73 83 0.30
Skin Type(FCS)*
1 & 2 42 50 0.40
3 & 4 99 107 0.60
5 & 6 126 116 0.52
Gender
Male 202 (75.7%) 204 (74.7%) 0.80
Female 65 (24.3%)69 (25.3%) 0.90
*Fitzgerald classification scale.

Melanonychia in Patients Infected with Human Immunodeficiency Virus Original Communication17
Table 2. Demographics and clinical characteristics of sub-
jects with and without melanonychia, number (%) or mean
(standard).
No Melanonychia
(N = 349)
Melanonychia
(N = 191) P value
Total = 540
(n) (%) (n) (%)
Age Groups
<39 177 50.72 79 41.40<0.01
40 - 49 113 32.40 70 36.70<0.01
50 - 59 44 12.61 31 16.230.13
> = 60 15 4.30 11 5.80 0.43
Test Across Age Groups 0.20
Race
White 105 30.10 5 2.62 <0.01
African-American 119 34.10 156 81.70<0.03
Hispanic 125 35.82 30 15.71<0.01
Test Across Race <0.01
Gender
Females 91 26.10 43 22.51<0.01
Males 258 73.93 148 77.50<0.01
Test Across Gender 0.36
HIV
Negative 213 61.03 60 31.41<0.01
Positive 136 39.00 131 68.600.76
Test Across HIV Status <0.01
Skin Type
1 & 2 85 24.40 7 3.70 <0.01
3 & 4 162 46.42 44 23.04<0.01
5 & 6 102 29.23 140 73.30<0.01
Test Across Skin Type <0.01
Table 3. Presentation of melanonychia and NRTIs prescrip-
tion use by HIV positive patients.
Total = 267 No Melanonychia
N = 136
Melanonychia
N = 131
(n) (%) (n) (%)
Zidovudine 33 24.30 39 29.80
Stavudine 34 25.00 24 18.23
Zidovudine and Stavudine 48 35.30 52 39.70
None 21 15.44 16 12.21
(42%) patients who had taken stavudine. Of those who had
taken both zidovudine and stavudine, 52 out of 100 (52%)
patients were diagnosed with melanonychia.
Table 4 presents the results of the logistic regression
model which adjusted for skin type. Participants with
melanonychia were 4.1 times more likely to be from the
group with HIV infection compared to the group without
HIV infection (OR = 4.1; 95% CI, 2.7 - 6.35; p < 0 .001).
Melanonychia was more likely to be found among par-
ticipants with darker skin coloration. Participants with
melanonychia were more likely to be in the medium col-
oration group compared to the lighter skin coloration
group (OR = 3.4; 95% CI, 1.4 - 8.0; p < 0.001), and par-
ticipants with melanonychia were far more likely to be in
the darker skin coloration group compared to the medium
skin coloration group (OR = 19.5; 95% CI, 8.4 - 45.0; p
< 0.001).
Table 5 illustrates the outcomes of the second logistic
regression model, with likelihood of melanonychia as
predicted by skin coloration, and by prescription or non-
prescription of either medication, and the interaction of
prescription of both. Patients with HIV infection who
were diagnosed with melanonychia were at 2.6 greater
odds of being from skin group 3 - 4 than from skin types
1 - 2. Patients with HIV infection who were diagnosed
with melanonychia were at 14.6 greater odds of being
from skin types 4 - 5 than from skin type groups 1 - 2.
HIV Patients who had taken zidovudine were 2.6 times
more likely to have melanonychia. If they had been ex-
posed to both zidovudine and stavudine there was no
difference in the presence of melanonychia. Unfortu-
nately, the length of time of zidovudine exposure was not
available. However, it seemed likely that patients who
had received both drugs had been started on zidovudine
and were switched to stavudine due to zidovudine intol-
erance and the exposure would have been brief.
Table 4. Relationship of presence of melanonychia and HIV
status or skin type.
Exposure Adjusted Odds Ratio 95% CI P value
HIV (N = 540)
Negative 1.0 (Reference) 1.0 (Reference)
Positive 4.14 2.71 - 6.35 <0.001
Skin type (N = 540)
1 & 2 1.0 (Reference) 1.0 (Reference)
3 & 4 3.40 1.44 - 8.00 <0.001
5 & 6 19.50 8.44 - 45.00 <0.001
Table 5. Melanonychia in HIV positive patients, as predi-
cated by skin type and nucleoside reverse transcriptase in-
hibitor exposure (N = 267).
Exposure Adjusted Odds
Ratio 95% CI P value
Skin type
1 & 2 1.0 (Reference) 1.0 (Reference)
3 & 4 2.63 1.05 - 6.62 0.04
5 & 6 14.62 5.70 - 36.00 <0.001
Zidovudine use
No 1.0 (Reference) 1.0 (Reference)0.03
Yes 2.65 1.07 - 6.55
Stavudine use
No 1.0 (Reference) 1.0 (Reference)0.75
Yes 1.16 0.46 - 2.96
Stavudine & Zidovudine use
No 1.0 (Reference) 1.0 (Reference)0.62
Yes 0.74 0.23 - 2.40

Melanonychia in Patients Infected with Human Immunodeficiency Virus Original Communication
18
4. Discussion
This study demonstrates that melanonychia is highly pre-
valent in HIV infected individuals with pigmented skin.
Given the much higher rate in HIV infected persons than
in the uninfected, it is quite possible that it will occur
after infection. As a result patients may connect it to their
HIV infection or to their taking antiretroviral medications.
Patients may be concerned that it is a serious medical
condition and/or they may think that it is cosmetically
displeasing. As a result patients may question the clini-
cian as to its origin and cause. Reassurance as to its be-
nign nature may help the patient to cope with their me-
dical concerns. However, patients may discover that me-
lanonychia has been associated with zidovudine use on
the internet and/or through information provided by non-
governmental organizations. If patients believe that zi-
dovudine or other HIV medications are causing a disfig-
urement of his or her nails, they may stop taking that
medication with negative consequences to their overall
well being and a reduction of their future treatment op-
tions. Physicians should be alert to this possibility in pa-
tients who raise questions about their melanonychia and
should reassure patients that it has not been linked to any
medication except zidovudine. If the patient is taking zi-
dovudine there are many other medications that can be
substituted for zidovudine (including stavudine).
Because patients may link melanonychia to antiretrovi-
ral therapy (even if they are not taking zidovudine) clini-
cians may wish to forewarn their patients that nail
changes might may occur and that it is not a reason to
stop taking their antiretrovirals. In forewarning or reas-
suring them, clinicians should emphasize that the condi-
tion is common in those who not HIV infected (21.8% of
those who were not infected in our study) and so its ap-
pearance should not be seen as something that will reveal
their HIV status nor is it a reasons to stop taking their an-
tiretrovirals. If a patient who is taking zidovudine has the
condition and is concerned about it and insists on chang-
ing medications they should be made aware that it will
take a long time for the lesions to disappear.
Clinicians should also recognize that while melanony-
chia is almost always a benign condition that is idiopa-
thic in origin, it is occasionally linked to more serious con-
ditions, particularly melanoma. Tosti et al. [20] offered
several clinical clues as to whether melanonychia requires
additional investigation for the presence of melanoma.
These were 1) discoloration bands in the nails that are
wider than 3mm and have irregular borders; 2) extension
of the band into the proximal and/or lateral nail fold
(Hutchinson’s sign); 3) a lesion with a triangular shape; 4)
nails that are split or have fissures; and 5) if the pigmen-
tation is not homogenous.
Given the extremely high prevalence of melanonychia
in these HIV positive patients (>49%) clinicians might
consider its presence as a potential clue to HIV positivity
in previously untested patients. Alone or together with
other signs or patient history, it might induce a discus-
sion of the need to rule out HIV infection. It is seldom
that a clinician has such a visible sign that might be in-
dicative of undiagnosed HIV infection.
5. Acknowledgements
This study was supported by the Baylor-UT Houston Center
for AIDS Research (CFAR), a program funded by the US
National Institutes of Health (NIH) (AI036211).
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