Vertical Transmission of HIV-1 in a Patient with a Rapid Decrease in HIV-1 Viral Load

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Summary

A 20 year-old female, 19 weeks pregnant, presented for routine prenatal care. Screening HIV-1 test was positive. Her CD4 count was 621 cells/mm, id and viral load was 3,179 copies/ml.  The patient was counseled. She acquired her HIV sexually. Although the patient understood her diagnosis and the risk to the fetus she came for only one appointment. She was given HIV medications but never took them.

At 39 weeks, the case manager tracked her down and convinced her to come to clinic. Because delivery could be imminent, she was admitted to start HIV therapy and optimize delivery. On admission CD4 was 816 cells/mm. id Viral load was 4,481 copies/ml. Her resistance test was pan-sensitive. She was started on raltegravir and combivir.

Five days after the start of therapy, her viral load decreased to 187 copies/ml. Seven days after admission she had an uncomplicated vaginal delivery. She received zidovudine during delivery. The baby was given zidovudine at birth. The initial PCR on the baby was negative but became positive at one month.

This case illustrates several problems in the management of pregnant HIV patients. Despite counseling and aggressive follow up, this patient was not keeping her medical appointments. Because of her non-compliance, our policy is to admit in order to ensure compliance with medications and optimize delivery.

Raltegravir was chosen to decrease transmission as rapidly as possible. The choice was based on data from the STARTMRK id  study which showed that raltegravir, with an optimized background, shortened virologic response more rapidly than efavirenz with an optimized background.

Despite having a viral load below 200 copies/ml, the baby acquired HIV-1, most likely during delivery as the first PCR was negative.  There are many possible explanations.

One possibility is that the viral load was below 1,000 copies/ml for only a couple of days prior to delivery. In the study by Garcia et al, id the rate of HIV-1 transmission was zero in women with less than 1,000 copies/ml. The authors did not specify the length of time the viral load was in that range. In a more recent study id  examining vertical transmission, mothers whose newborn was HIV negative, started antiretroviral therapy on the average at 18 weeks of gestation compared to 27 weeks for mothers who transmitted HIV to their newborn.

Another possibility is that the decrease in viral load in the peripheral blood does not reflect a similar decrease in tissues or in the vaginal canal.  In a study by Gardella et al id  genital HIV shedding in pregnant women was higher than in their non-pregnant counterpart. In addition HIV was present in vaginal secretions even though the plasma viral load was negative: HIV DNA, HIV RNA transcripts, and cell free HIV RNA were present in cervico-vaginal secretions in 56%, 22%, and 43% of pregnant women with undetectable plasma viral load.

The important question remains: when an HIV pregnant patient presents in labor with a viral load below 1,000 copies/ml, but the duration of antiretroviral therapy is “short”, should the mother be encouraged to have a C-section?

References

  1. Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naïve patients with HIV-infection: a multicentre double-blind randomized controlled trial. Lancet 2009; 374:796-806

  2. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group NEJM 1999; 341:394-402.

  3. Tubiana R, Le Chenadec J, Rouzioux C, Mandelbrot L, Hamrene K, Dollfus C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load < 500 copies/mL at delivery: a case-control study nested in the French Perinatal Cohort (EPF-ANRS CO1). Clin Infect Dis 2010; 50:585-596.

  4. Gardella B, Roccio M, Maccabruni A, Mariani B, Panzeri L, Zara F, et al. HIV shedding in cervico-vaginal secretions in pregnant women. Curr HIV Res 2011; 9:313-320.