Analysis of prevalence of HIV-1 drug resistance in primary infections in the United KingdomBMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7294.1087 (Published 05 May 2001) Cite this as: BMJ 2001;322:1087
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Editor- Transmission of HIV-1 and drug resistant HIV-1 is increasing
in the UK. Resistance testing in recently infected people is recommended
to monitor the prevalence of transmitted drug resistance and optimise
initial treatment choices. [1, 2] We highlight the potential impact of
the increasing availability of antiretroviral therapy (ART) in resource
poor countries on transmission of drug resistance in the UK using a case
A middle-aged woman from a Southern African country was referred
as a newly diagnosed case of HIV in July 2001 following a life insurance
She reported she was unaware of her HIV status.
HIV-1 viral load was 130 000 copies/ml and her CD4 count 110
cells/mm3, and zidovudine/lamivudine/efavirenz combination therapy was
initiated. However she did not respond to therapy with viral loads of
89000 and 75000 copies/ml, and CD4 counts of 180 and 160 cells/ml at weeks
4 and 8 following initiation of therapy, respectively, as shown in Figure
The presence of a number of mutations conferring resistance to
nucleoside and non-nucleoside reverse transcripase inhibitors in plasma
virus from week 10 prompted us to test a sample of plasma taken prior to
therapy. This demonstrated the presence of a mutation in the protease gene
(V82A) along with mutations M41L, L74V, V75I, L100I, M184I, Y188L, and
T215Y in reverse transcriptase indicating multidrug resistance. .
This degree of resistance is usually associated with previous
exposure to treatment, so she was questioned regarding her treatment
history. She acknowledged knowing her HIV status before coming to the UK,
but had not divulged this due to issues pertinent to her status in the UK.
Additionally, she admitted to receiving a three-drug combination in her
native country, which she continued to take whilst in the UK via mail
shipments from a private clinic in her native country. When she ran short
of tablets, she would take less than the prescribed dose to keep her
supply going for longer.
HIV infected individuals living in sub-Saharan Africa and elsewhere
in resource poor settings will have greater access to ART.  While this
is welcomed it. It is important that it is accompanied by the ability to
purchase and secure a stable supply of therapy. 
Our patient seriously compromised her treatment and, from a public
health perspective, others were exposed to serious risk of transmission of
multi-drug resistant HIV. Together these issues beg the question of
whether more intense questioning plus reassurance about disclosure of
previous therapy should be routinely undertaken prior to initiating anti-
HIV therapy in those patients from countries where anti-HIV therapy is
becoming more widely available.
1.Health protection agency. CDR weekly, March. 2003
2.UK collaborative group on monitoring the transmission of HIV drug
resistance. Analysis of prevalence of HIV-1 drug resistance in primary
infections in the United Kingdom. BMJ 2001; 322:1087-1088
3.Hirsch MS, Conway B, D`Aquila RT, et al. Antiretroviral drug
resistance testing in adults with HIV-1 infection: Implications for
clinical management. JAMA 2000; 283:2417-26.
4.Report on the global HIV/AIDS epidemic. UNAIDS, July 2002
5.Byakika-Tusiime J, Oyugi JH, Tumwikirize WA. et al. Ability to
purchase and secure stable therapy are significant predictors of non-
adherence to Antiretroviral therapy in Kampala, Uganda. 10th Conference on
retroviruses and opportunistic infections. Boston MA, 2003, abstract
The patient whose case is described has given her signed informed consent to publication.
Competing interests: No competing interests
EDITOR- The UK collaborative group on monitoring the transmission of
HIV Drug resistance report an estimated prevalence of transmitted HIV drug
resistance in the year 2000 of 27%1. In an on-going study of acute primary
HIV infection at St. Mary's Hospital we have identified 28 seroconverters
since January 2000. All patients sequenced to date (15/28) have no
evidence of drug resistant mutations in either RT or protease prior to
commencing antiretroviral therapy. This is substantiated by the clinical
response to therapy, with all subjects achieving an undetectable viral
load after commencing antiretroviral therapy.
The disparity in our findings is interesting, as the two cohorts are
comparable. Our cohort was predominantly infected with clade B viruses
(13/15). The median age was 30.5 yrs (ICQ 18.5 - 42.5). All infections
were transmitted sexually, except for one IVDU.
A possible explanation for the disparity is that seven of our
patients were infected abroad, where anti-retroviral therapy is less
readily available. However, whereas Pillay et al. use an eighteen month
window of sampling to define seroconversion, we have used a more stringent
definition of 6 months. This should allow us to detect more transmitted
mutations, as in the absence of therapy these are often lost with time due
to reduced viral fitness.
In addition, we have found that caution needs to be applied when
estimating the impact of codon changes in pol prior to commencing therapy
in drug-naïve subjects. In a cohort of African patients treated at St.
Mary's, 30% of codons in RT and 37% in protease were polymorphic compared
with wild-type clade B HIV-1 and of these, 6% and 22%, respectively,
occurred at codons associated with resistance. However, despite these
changes, no single mutation impacted on clinical outcome on CART2.
The existence of these cohorts supports the high incidence of new
infections and lack of safe-sex awareness. Although approaches to
encourage safer sexual behaviour are urgently needed, our data suggest
that the transmission of drug resistance is a secondary, although
Lecturer in HIV
MRC Research Fellow
Jefferiss Professor of Communicable Diseases
Dept of HIV/GUM,
Jefferiss Trust Laboratories,
Imperial College School of Medicine,
St. Mary's Hospital,
1 Analysis of prevalence of HIV-1 drug resistance in primary
infections in the United Kingdom. BMJ 2001;322:1087-1088 (5 May).
2. The Impact of Baseline Polymorphisms in RT and Protease on the
Outcome of HAART in HIV-1 Infected African Patients. A. J. Frater, A.
Beardall, K. Ariyoshi, et al. AIDS (2001) In Press.
Competing interests: No competing interests