|
Indian Pediatr 2009;46: 53-56 |
![](../Home_files/coverin.gif) |
Rapid Progression of HIV Infection in Infancy |
N Poorana Ganga Devi, R Shenbagavalli, K Ramesh, S
Nataraja Rathinam*
and Soumya Swaminathan
From Tuberculosis Research Center, Chennai; and
*Institute of Child Health and Research Center,
Government Rajaji Hospital, Madurai;
Tamil Nadu, India.
Correspondence to: Dr Soumya Swaminathan, Scientist F,
Tuberculosis Research Centre,
Mayor V R Ramanathan Road, Chetput, Chennai 600 031, India.
E-mail: [email protected]
Manuscript received: January 10, 2007;
Initial review completed: February 8, 2008;
Revision accepted: March 24, 2008. |
Abstract
Transmission of HIV from mother to child can occur in
utero, during labor or after delivery via breast feeding. Data on the
fate of babies born with HIV in India are scarce. We present details of
25 infants with perinatally acquired HIV infection (virologically
confirmed) to highlight the observed high rate of morbidity and
mortality within the first 18 months of life. Our findings of rapid
disease progression among perinatally infected HIV positive children
underline the importance of early diagnosis and treatment.
Keywords: HIV, India, Infant, Progression, Transmission.
|
T he natural history of
pediatric HIV infection in infants is well documented in many countries
showing a characteristic bimodal pattern of disease progression(1,2).
Studies from Africa have shown 26-45% mortality by 1 year of age and up to
89% by 3 years of age(3-5). There is little data from India regarding the
clinical course of exposed babies followed from birth(6,7). We describe
the clinical features and outcome of 25 infants, confirmed to be HIV-1
positive by DNA-PCR.
Methods
This was a prospective,
observational study conducted in Tuberculosis Research Centre (TRC)
Clinics of Madurai and Chennai between March 2004 and June 2007. Infants
born to HIV-1 positive women at Chennai and Madurai were referred to TRC
for confirmation of diagnosis by DNA-PCR. 19 infants were referred to TRC
Madurai unit while 6 were referrals from hospitals in Chennai. The study
had Institutional Ethics approval and informed consent was obtained from a
parent/guardian. Clinical examination including anthropometry was done and
blood drawn for DNA-PCR and CD4/CD8 counts. CD4 and CD8 counts were
measured on a Coulter Epics flow cytometer (Beckman Coulter, USA) using a
standard 4-colour protocol. DNA-PCR was done using the Roche AMPLICOR
HIV-1 DNA Test Version 1.5.
Detailed counseling was
provided including the feeding options; however the choice was left to the
mother. Babies were followed every 3 months, till 18 months of age. All
babies were given cotrimoxazole 5mg/kg orally daily and opportunistic
infections were managed appropriately. Diagnoses of opportunistic
infections were based on clinical and disease specific criteria. Patients
were referred to government ART centres in Madurai and Chennai but
pediatric formulations became available only in November 2006 and most of
these infants could not access ART, at the time of this study.
Results
The baseline
immunological profile and age at the time of presentation, sex, type of
feeding, CD4 counts and CD4/CD8 ratio, status at the time of writing the
report (October 2007) and cause of death are shown in Table I.
The mean age at presentation was 154 days (SD 68). DNA-PCR was found
positive in 21 infants at presentation. Four infants whose test was
negative and CD4% was high at baseline, had a fall in CD4% along with a
positive PCR at 6 months of age. All infants were delivered vaginally
except one. Fourteen mother-infant pairs received nevirapine prophylaxis
as per the prevention of mother to child transmission guidelines of
National AIDS Control Organization. Eleven infants were breast-fed, 3 were
artificially fed while nine were given mixed feeds. Feeding details for 2
infants were not known. All four infants who showed a later conversion of
DNA-PCR to positive result were given mixed feeds.
Clinical and Immunological Features of 25 HIV Infected Infants
S.
No |
Age
(days) |
Sex |
CD4% |
CD4
count
(cells/
mm3) |
CD4/
CD8
ratio |
Feeding
choice |
Clinical features |
Anti-
retroviral
treatment |
Outcome |
1 |
36 |
M |
71* |
5807 |
4.73 |
Mixed |
Hepatosplenomegaly, TB, oral thrush |
No |
Died |
|
|
|
28** |
1065 |
0.67 |
|
|
|
2 |
12 |
F |
63* |
3847 |
4.2 |
Breast |
Bronchopneumonia |
No |
Died |
|
|
|
24** |
2019 |
0.5 |
|
|
|
3 |
50 |
F |
67* |
4159 |
2.79 |
Breast |
LRI |
No |
Alive |
|
|
|
26** |
1265 |
0.68 |
|
|
|
4 |
18 |
F |
56* |
4436 |
2.07 |
Bottle |
Skin lesion,diarrhoea |
yes |
Alive |
|
|
|
10** |
1224 |
0.48 |
|
|
|
5 |
45 |
M |
NA |
NA |
NA |
Breast |
Bronchopneumonia |
No |
Died |
6 |
75 |
M |
26 |
890 |
0.65 |
Mixed |
Seizures |
No |
Died |
7 |
50 |
M |
18 |
626 |
0.37 |
Breast |
Bronchopneumonia |
yes |
Died$ |
8 |
80 |
M |
39 |
3747 |
0.975 |
Mixed |
Hepatosplenomegaly, LRI |
yes |
Alive |
9 |
120 |
M |
12 |
525 |
0.21 |
Breast |
Diarrhea |
No |
Died |
10 |
180 |
M |
NA |
NA |
NA |
Bottle |
Diarrhea |
No |
Died |
11 |
45# |
F |
38 |
6207 |
2.24 |
Mixed |
Bronchopneumonia, CMV retinitis |
yes |
Died$ |
12 |
150 |
F |
19 |
3158 |
0.4 |
Mixed |
Diarrhea, oral thrush |
No |
Alive |
13 |
150 |
M |
NA |
NA |
NA |
Breast |
LRI |
No |
Alive |
14 |
300 |
F |
39 |
3902 |
1.18 |
Breast |
LRI |
No |
Alive |
15 |
210 |
F |
53 |
4025 |
1.51 |
Breast |
LRI, oral thrush |
No |
Alive |
16 |
365 |
M |
28 |
918 |
0.5 |
Mixed |
Diarrhea,vomiting,seizures, fever |
No |
Alive |
17 |
42 |
F |
9 |
894 |
0.14 |
Mixed |
Diarrhea |
No |
died |
18 |
270 |
M |
19 |
1456 |
0.37 |
Mixed |
Vomiting and diarrhea |
No |
died |
19 |
365 |
F |
8 |
301 |
0.12 |
Breast |
LRI |
No |
died |
20 |
150 |
M |
28 |
2551 |
0.74 |
Bottle |
Bronchopneumonia, FTT, diarrhea |
No |
Alive |
21 |
180 |
F |
14 |
1037 |
0.2 |
NA |
Delayed milestones, FTT, diarrhea |
Yes |
Alive |
22 |
300 |
F |
17 |
1989 |
0.71 |
Breast |
LRI |
No |
Alive |
23 |
300 |
M |
19 |
1202 |
0.44 |
Breast |
Delayed milestones, FTT |
No |
Alive |
24 |
48 |
F |
8 |
212 |
0.16 |
NA |
LRI, diarrhea |
No |
Died |
25 |
300 |
F |
39 |
1597 |
0.975 |
Breast |
LRI, FTT, oral thrush, delayed milestones |
No |
Alive |
*CD4 at the time of registration (DNA-PCR found to be negative);
** CD4 at the time of HIV suspicion (Repeat DNA-PCR found to be positive); NA–Not available;
# LSCS; $ soon after ART initiation; FTT: Failure to thrive.
The mean (SD) birth
weight was 2.6(0.5) kg. The mean (SD) CD4 count was 1855 (1503) cells/mm 3.
Mean (SD) CD4% was 23.6 (12), CD8 3081 (1633) cells/mm3, and CD8 % 44 (14)
at the time of HIV-1 positivity. The CD4/CD8 ratio (mean 0.64±0.50) was
less than 1 and the hemoglobin was less than 10 g/dL (mean 9.47±1.65) in
all infants.
Twelve children died
before 18 months of age. Five children received antiretroviral treatment,
of whom 2 died and 3 are surviving. Of 20 children who did not receive
ART, 10 died and 10 are under follow up. The most common diagnoses during
the course of the disease are shown in Table I.
Discussion
Of the 25 HIV-1 infected
infants enrolled in this study, 10 died before antiretroviral treatment
could be initiated and 2 died shortly after initiation of ART. This
suggests that a substantial proportion of HIV-1 positive children infected
perinatally in India are rapid progressors and will die in infancy unless
diagnosed and treated early.
We observed that four
children who initially had a CD4/CD8 ratio >1.0 and were later found to
have a ratio <1.0 had become HIV positive. These infections are likely to
have occurred due to breastfeeding. The practice of breastfeeding has been
shown to diminish the long-term efficacy of perinatal prophylactic
antiretroviral therapy(8). Two African studies have found that infants
assigned to be formula fed or breastfed had similar mortality rates and
incidence of diarrhea and pneumonia during the first 2 years of life.
However, HIV-1-free survival at 2 years was significantly higher in the
formula arm(9,10). Replacement feeding with animal milk or formula should
be encouraged whenever it is acceptable, feasible, affordable, sustainable
and safe. Our preliminary observation that the CD4/CD8 ratio can be used
as a supporting diagnostic test for HIV-1 needs confirmation in controlled
trials.
The WHO guidelines 2006
recommend ART be initiated for infants <12 months who have CD4 <25% or CD4
count <1500 cells/mm 3(11). In
our study, some of the infants who subsequently died had CD4 counts above
this cut-off, suggesting that these may not always be predictive of
outcome. Children <1 yr of age are at high risk for disease progression,
and immunologic and virologic tests to identify those likely to develop
rapidly progressive disease are less predictive than in older children.
Therefore infants should be treated with antiretroviral agents as soon as
the diagnosis of HIV infection is confirmed, regardless of clinical or
immunologic status, or viral load(12). Recent clinical trials suggest that
initiation of ART before 12 weeks of age reduces early mortality by
75%(13). Though long-term HAART allows for restoration of CD4+ cell counts
and control of viral loads in HIV-1-infected children, initiating HAART
after severe immunosuppression had occurred is detrimental for the
restoration of cell mediated immunity(14). In summary, our experience with
HIV infection in Indian infants suggests that without early diagnosis and
treatment, the outcome is likely to be poor in a substantial proportion.
What This Study Adds?
• A large proportion of children born with HIV-1
infection in India are rapid progressors.
|
Acknowledgments
The authors gratefully acknowledge the assistance
provided by Ms Gomathy, Nutritionist, in nutritional assessment of the
children and Mr Thiruvalluvan, Medical Social Worker in sociological
assessment and follow-up of mothers. We are grateful to the staff members
of the clinical and HIV laboratory divisions for their cooperation and Ms
D Kalaivani for secretarial assistance. We thank Dr V Kumaraswami, Deputy
Director (Sr Grade) for his critical comments on the manuscript and the
Director, Dr P R Narayanan for his encouragement and support.
Contributors: NPGD and SS conceived and
coordinated the study and drafted the manuscript. RS and SNR were involved
in patient recruitment and follow-up and KR performed the laboratory
investigations.
Funding: Indian Council of Medical Research.
Competing interests: None Stated.
References
1. Chearskul S, Chotpitayasunondh T, Simonds RJ,
Wanprapar N, Waranawat N, Punpanich W, et al. Bangkok
Collaborative Perinatal HIV Trans-mission Study Group. Survival, disease
mani-festations, and early predictors of disease progression among
children with perinatal human immunodeficiency virus infection in
Thailand. Pediatrics 2002; 110 (2Pt 1): e25.
2. Abrams EJ, Wiener J, Carter R, Kuhn L, Palumbo P,
Nesheim S, et al. Perinatal AIDS Collaborative Transmission
Study (PACTS) Group. Maternal health factors and early Pediatric
antiretroviral therapy influence the rate of perinatal HIV-1 disease
progression in children. AIDS 2003; 17: 867-877.
3. Dabis F, Elenga N, Meda N, Leroy V, Viho I, Manigart
O, et al; DITRAME Study Group. 18-Month mortality and perinatal
exposure to zidovudine in West Africa. AIDS 2001; 15: 771-779.
4. Newell ML, Coovadia H, Cortina-Borja M, Rollins N,
Gaillard P, Dabis F; Ghent International AIDS Society (IAS) Working Group
on HIV Infection in Women and Children. Mortality of infected and
uninfected infants born to HIV-infected mothers in Africa: a pooled
analysis. Lancet 2004; 364: 1236-1243.
5. Spira R, Lepage P, Msellati P, Van De Perre P, Leroy
V, Simonon A, et al. Natural history of human immunodeficiency
virus type 1 infection in children: a five-year prospective study in
Rwanda. Mother-to-Child HIV-1 Transmission Study Group. Pediatrics 1999;
104: e56.
6. Shah I. Age related clinical manifestations of HIV
infection in Indian children. J Trop Pediatr 2005; 51: 300-303.
7. Shah SR, Tullu MS, Kamat JR. Clinical profile of
pediatric HIV infection from India. Arch Med Res 2005; 36: 24-31.
8. McGowan JP, Shah SS. Prevention of perinatal HIV
transmission during pregnancy. J Antimicrob Chemother 2000; 46: 657-668.
9. Mbori-Ngacha D, Nduati R, John G, Reilly M,
Richardson B, Mwatha A, et al. Morbidity and mortality in breastfed
and formula-fed infants of HIV-1-infected women: A randomized clinical
trial. JAMA 2001; 286: 2413-2420.
10. Nduati R, John G, Mbori-Ngacha D, Richardson B,
Overbaugh J, Mwatha A, et al. Effect of breastfeeding and formula
feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000;
283: 1167-1174.
11. Antiretroviral therapy of HIV infection in infants
and children: towards universal access-WHO Guidelines 2006. Available
from: http://www.who. int/hiv/pub/guidelines/paediatric020907.pdf.
Accessed on 15th December 2007.
12. Yogev R, Chadwick EG. Acquired Immuno-deficiency
Syndrome (Human Immunodeficiency Virus). Nelson Behrman RE, Kliegman RM,
Jenson HB. Textbook of Pediatrics. 17th Edition. Philadelphia: Saunders;
2004. p. 1118.
13. Violari A, Cotton M, Gibb D, Babiker A, Steyn J,
Jean-Phillip P, et al. Antiretroviral therapy initiated before 12
weeks of age reduces early mortality in young HIV-infected infants:
evidence from the Children with HIV Early Antiretroviral Therapy (CHER)
Study. Abstract WESS 103-4th IAS conferences on HIV Pathogenesis,
Treatment and Prevention July 2007, Sydney, Australia.
14. Resino S, Resino R, Micheloud D, Gutierrez GD, Leon JA, Ramos JT,
et al; Spanish Group of Pediatric HIV Infection. Long-term effects
of highly active antiretroviral therapy in pretreated, vertically HIV type
1-infected children: 6 years of follow-up. Clin Infect Dis 2006; 42:
862-869. |
|
![](../Home_files/iap.jpg) |
|