HIV Treatment Bulletin - Vol. 6, No. 7, July 2005
Polly Clayden, HIV i-Base

In a letter in the 10th June issue of AIDS, Deborah Cohan and co-workers describe a case in which an infant was infected with multi-drug resistant HIV, despite undetectable plasma HIV-1 RNA levels in the mother. [1] The authors note that the mother was receiving a regimen in which the drug to which the patient was fully sensitive, T-20, may have limited distribution to the genital tract.

This was the patient’s eighth pregnancy and she had two children. She presented for prenatal care at the clinic at 7 weeks gestation. Since 1996 she had been intermittently adherent to several combinations of antiretrovirals and was experienced in all the then available three classes. When she presented she was receiving 3TC, abacavir and lopinavir/ritonavir and had a viral load of 29,712 copies/ml and a CD4 cell count of 323 cells/mm³.

Genotypic resistance testing revealed multidrug resistance (reverse transcriptase: M41L, L74V, K103N, M184V, and T215Y; protease: L10F, L33F, I54V, L63P, A71V, V82A, I84V). Phenotypic resistance testing confirmed high level resistance to most antiretrovirals. The patient was admitted to hospital for directly observed therapy at 33 weeks. Her treatment was changed to 3TC, abacavir, tenofovir and T-20. When labour was induced at 37 weeks, the patient’s HIV-1 RNA level was undetectable. She received Intravenous AZT during labour, and the baby received AZT, 3TC, lopinavir/ritonavir and nevirapine after delivery.

The infant’s DNA PCR at birth was indeterminate but at 8 days the baby’s HIV-1 RNA level was 6,240 copies/ml. Genotyping revealed the presence of multiple protease and reverse transcriptase mutations but no known T-20 associated mutations.

The authors speculate that transmission could be explained be several mechanisms:

• Transmission may have occurred before the initiation of the T-20 regimen but the HIV-1 DNA result suggesting transmission just before labour;
• Transmission may have occurred at the time of delivery despite the patient’s undetectable HIV RNA levels. Although T-20 containing combinations have been shown to produce undetectable levels in plasma, its activity in other compartments are undefined but it does not appear to cross into male genital fluids. Theoretically T20 resistant replication may have occurred within the genital tract leading to transmission at delivery.

The authors note that T-20 should be an ideal candidate for preventing mother to child transmission (and success has been described in another case study. [2, 3] Testing these hypotheses will require longitudinal assessments of HIV-1 in multiple compartments in patients receiving salvage regimens that contain T-20.

They write: “ As the role of the genital compartment in perinatal transmission becomes further elucidated, decisions regarding the preferred delivery route may be guided by genital viral load measurements, and, as suggested here, knowledge of the relative capacity of a given drug regimen to penetrate the genital compartment.”

This clinic has provided prenatal care for 165 women since 1995 and has pioneered treatment of HIV positive women with antiretrovirals during pregnancy many of whom have had multi drug resistant HIV-1 at presentation. This is the first case since then in which they were unable to prevent mother to child transmission of HIV.

References

Comment

This single case study highlights the difficulty of treating multi-drug resistant HIV in any setting.

The previously reported case study was effective, but with no comment can really be made on use of T-20 during pregnancy on such low numbers.

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