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The impact of maternal highly active antiretroviral therapy and short-course combination antiretrovirals for prevention of mother-to-child transmission on early infant infection Rates at the Mulago National Referral Hospital in Kampala, Uganda, January 2007 to May 2009
Global Health Sciences Literature Digest
Published March 28, 2011
Journal Article

Namukwaya Z, Mudiope P, Kekitiinwa A, Musoke P, Matovu J, Kayma S, Salmond W, Bitarakwate E, Mubiru M, Maganda A, Galla M, Byamugisha J, Fowler MG. The impact of maternal highly active antiretroviral therapy and short-course combination antiretrovirals for prevention of mother-to-child transmission on early infant infection Rates at the Mulago National Referral Hospital in Kampala, Uganda, January 2007 to May 2009. J Acquir Immune Defic Syndr. 2011; 56: Number, 69-75.

In Context

With implementation of highly effective antiretroviral therapy and prophylaxis, mother-to-child transmission of HIV in the US and Europe has been reduced to less than 2%. However, implementation of prevention of mother-to-child transmission (PMTCT) programs in resource-poor settings has been challenging, with only an estimated 45% of pregnant women living with HIV receiving antiretroviral (ARV) PMTCT interventions.(1) In Uganda, despite comprehensive policies to promote integration of mother and child health (MCH) services with HIV counseling and testing, ARV prophylaxis and treatment, and early infant diagnosis, only 34% of pregnant HIV-infected women received ARVs for PMTCT.(2)

Objective

To describe the ARV drugs used in the Mulago PMTCT program and to determine the impact of these interventions on early infant HIV infection rates.

Setting

Three antenatal care (ANC) clinics, three labor/delivery units and one postnatal clinic, and Mulago Hospital in Kampala, Uganda.

Study Design

Retrospective cohort study.

Population

HIV-infected pregnant women and their HIV-exposed infants.

Outcomes

Early infant HIV infection rate as determined by a positive DNA polymerase chain reaction (PCR) result at first postnatal visit between six weeks and three months of age.

Methods

Women who tested positive with rapid HIV tests during their first ANC visit or who had known HIV positive status, received CD4 testing and were followed through delivery and the postnatal period. Infants were assessed for HIV infection at six weeks of age with DNA PCR. Data were collected as part of an ongoing PMTCT program.

Women received regimens according to the Uganda Ministry of Health (MOH) guidelines,(3) which includes 1) HAART if CD4 <350 cells/µl and/or WHO Clinical Stage III or IV (From mid 2007 and before, CD4 cutoff for HAART was 250 cells/µl; most women received zidovudine/lamivudine/nevirapine, or ZDV/3TC/NVP, as first-line treatment regimen), 2) ZDV 300 mg twice daily from 28 weeks gestation plus single dose nevirapine (sdNVP) at onset of labor if CD4 ≥350 cells/µl and WHO Clinical Stage I or II, 3) ZDV 300 mg plus 3TC 150 mg twice daily from 33 weeks of gestation, plus sdNVP at onset of labor if CD4 ≥350 cells/µl and WHO Clinical Stage I or II, and 4) mothers identified as HIV-infected in labor, received sdNVP only. From 2009, women who reported in labor received sdNVP and were started on ZDV/3TC. Women who took sdNVP during labor/delivery were also given ZDV/3TC for one week after delivery. HIV exposed newborns received sdNVP and one week of ZDV.

Women were strongly encouraged to deliver at the Mulago Hospital and to return with the infants for a six week postnatal follow-up visit. Those who were not part of another HIV care program were enrolled into the PMTCT follow-up clinic for long-term HIV care. Additional strategies to get mothers to return to the hospital included use of “peer” mothers, telephone reminders (50% had telephone contacts), home visits for the women on highly active antiretroviral therapy (HAART), treatment supporters for clinic visits, and psychosocial support by counselors and peer mothers.

Results

From January 2007 to May 2009, 99.7% (74,952/75,159) of new ANC attendees had their HIV status determined through both rapid HIV testing and those who presented with known HIV status. Overall, 10% were HIV-infected, of whom 62% received combination ARVs, including 23% who received HAART, 17% AZT/3TC/sdNVP, and 23% AZT/sdNVP. An additional 34% of women received sdNVP and 3% received no ARVs. The overall median gestational age at first ANC visit was 28 weeks. Sixty percent of HIV-infected women returned to the hospital at labor/delivery, of whom 59% were enrolled into long-term care. However, less than 50% of these women returned with their infant to the postnatal clinic before three months of age, but among those 2,338 infants who did return, 99% received DNA PCR testing at a median age of 6.4 weeks (interquartile range 6.1-7.1). Most women (>90%) breastfed their infants.

Early infection rates were highest among infants whose mothers received no ARVs (36.4; 95% CI: 17.2-59.3) or only sdNVP at labor and delivery (11.2; 95% CI: 8.1-14.8). Similar rates were seen for infants whose mothers received ZDV plus sdNVP (4.6; 95% CI: 3.2-6.4) and ZDV/3TC plus sdNVP (4.9; 95%CI: 3.1-7.2), and the lowest rates were among infants whose mothers took HAART during the pregnancy (1.7, 95% CI: 0.8-2.8). The overall early infant infection rate was 5.0 %(95% CI: 4.1-5.9). Results of regression analysis, adjusting for marital status, education level, maternal CD4, maternal ARV and sex of the baby, found that use of maternal ARV significantly reduced the risk of infection, with the lowest risk among those that received HAART (incident risk ratio [IRR] 0.10, 95%CI: 0.03-0.38). Male infants were significantly less likely to be infected compared to female (IRR 0.56; 95%CI: 0.33-0.93).

Results

Data from this large urban hospital demonstrate that it is possible to achieve low rates of early infant HIV infection rates (<5%) through delivery of comprehensive PMTCT services and combination ARVs in low resource settings. Women who received HAART for their own care had the lowest early infant infection rates of <2%.

Study Quality

This study provides data from a large urban hospital in Kampala, Uganda with an HIV prevalence of 10% in pregnant women. However, there was a large loss to follow-up before delivery and at postnatal care, limiting representativeness of results. Only early infection rates were presented. Late infection rates among a predominantly breastfeeding population were not presented.

Programmatic Implications

These data demonstrate the effectiveness of an adequately resourced PMTCT program, which result in high uptake of maternal rapid HIV testing, combination ARV drugs and low early transmission rates. These data are also consistent with results from other observational studies in Botswana (4) and Zambia.(5) However, there were large losses to follow-up among both pregnant HIV-infected women and their infants, despite efforts to retain women and infants in care. Additional strategies beyond peer support and use of mobile phone reminders are needed to improve retention. Programs need adequate funding and support to integrate PMTCT services successfully into MCH services. With adequate staffing and ongoing training, these programs can substantially reduce HIV transmission and improve overall infant survival.

References

  1. AIDS Epidemic Update. 2009:6
  2. UNAIDS/WHO/UNICEF. Epidemiological fact sheets on HIV and AIDS, 2008 updates.
  3. Uganda Ministry of Health. Policy guidelines for prevention of other-to-child transmission of HIV; revised edition August 2006;circular update new guidelines on use of ARV for prevention of mother to child transmission of HIV (PMCTC) in Uganda, December 22, 2008, Republic of Uganda, Ministry of Health.
  4. Creek T, Tanuri A, Smith M, et al. Early diagnosis of human immunodeficiency virus in infants using polymerase chain reaction on dried blood spots in Botswana's national program for prevention of mother-to-child transmission. Pediatr Infect Dis J 2008; 27:22-6
  5. Torpey K, Kasonde P, Kabaso M, et al. Reducing pediatric HIV infection: estimating mother-to-child transmission rates in a program setting in Zambia. J Acquir Immune Defic Syndr. 2010 Aug 1;54(4):415-22
  6. World Health Organization: Rapid advice: use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. WHO. 2009, Geneva, Switzerland
  7. .