Rapid Progression of HIV Infection in Infancy

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Indian Pediatr 2009;46: 53-56

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: doctorsoumya@...

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.

The 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.

TABLE I

Clinical and Immunological Features of 25 HIV Infected Infants

S.No

Age(days)

Sex

CD4%

CD4count(cells/mm3)

CD4/CD8ratio

Feedingchoice

Clinical features

Anti-retroviraltreatment

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/mm3. 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/mm3(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, 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, G, Reilly M, 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, G, Mbori-Ngacha D, 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). 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- 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.