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Unexpected resistance in an African immigrant: lessons for the unwary
  1. U R Natarajan,
  2. M Fisher
  1. Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
  1. Correspondence to:
 U R Natarajan
 Brighton and Sussex University Hospitals NHS Trust, Brighton, UK; ushawriteaol.com

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The number of people emigrating from Africa to the United Kingdom has been escalating. They contribute to the increasing number of heterosexuals with HIV in the United Kingdom.1 Increasingly, developing countries are improving their access to antiretroviral drugs through global funds for AIDS and other sources. It is well known that resistance to antiretrovirals develops where therapy is either suboptimal or adherence is imperfect, and that such resistance is associated with poor outcome.2

A Zimbabwean man aged 47 was admitted to the Royal Sussex County Hospital, in August 2001 with lobar pneumonia. He had excellent response to the appropriate antibiotics. He reported receiving treatment for tuberculosis twice in the past. He had a positive HIV antibody test which was done after pretest discussion. The baseline CD4 count and viral load were consistent with advanced infection, 20 ×106/l (2%) and 134 000, respectively.

He was commenced on combination antiretroviral therapy with combivir and efavirenz, and had a good initial virological response with a drop of his viral load to 1230 (3.09 logs) in 2 weeks. However, his viral load rebounded to 71 000 at 6 weeks. He was thought to be non-adherent to the antiretrovirals at this stage and was questioned extensively regarding adherence. He claimed 100% adherence to his medication and denied any missed or late doses. Interactions with prescribed and non-prescribed medications were excluded.

At this stage a genotypic resistance test was organised from the sample, with a viral load of 71 000 and he was admitted to the local respite unit (The Sussex Beacon) for directly observed therapy (DOT). The viral load after 2 weeks of DOT was 240 000.

A genotypic resistance test revealed the following mutations: K65R, D67N, K70R, K103N, M184V, G190A, T215F, K219Q, suggesting that he had extensive resistance to nucleoside analogues and to all non-nucleosides. When he was reviewed with his resistance test result, he still denied any knowledge of HIV testing or treatment in Zimbabwe, but identified combivir tablets as part of his anti-tuberculosis medication. Genotypic resistance testing of his archived initial sample before his commencement of treatment showed: M41L, V118I, M184V, T215F.

He was then commenced on a salvage regimen of didanosine, tenofovir, kaletra, and sauquinavir HG and had a good virological response with a viral load drop of 1350 (3.13 logs) in 4 weeks.

It remains uncertain whether in this case the individual had been aware of his HIV status. It is possible that antiretroviral medications may have been included as part of an unorthodox anti-tuberculosis regimen, given the high co-infection rate in Zimbabwe, without the individual having been informed. Alternatively, the individual may have been unwilling to disclose his status for fear of rejection of his legal claim to stay in the United Kingdom or for other sociocultural reasons.

Either way, the choice of initial therapy was inappropriate, given the underlying resistance to reverse transcriptase analogues, and resulted in the subsequent rapid accumulation of NNRTI resistance.

While it is known that acquired resistance mutations may disappear with time after discontinuation of therapy3 had a genotype resistance test been performed at presentation in this case a more effective regimen would have been selected. Current BHIVA guidelines recommend resistance testing before therapy only in the context of demonstrable transmitted drug resistance.

As antiretroviral therapies become increasingly available in developing countries and while stigma regarding disclosure of HIV status for immigrants remains, we believe that similar cases will occur.

We strongly suggest that immigrants with a new HIV diagnosis should be closely questioned regarding previous testing and treatment, and also baseline resistance testing should be routinely considered.

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