The incidence of AIDS-defining events (ADEs) has fallen dramatically across Europe during the HAART era according to new research presented at this week's 39th ICAAC in San Francisco. Data from 7,200 participants of the EuroSIDA cohort show that 31 people in 100 became ill within a year in 1994, but that this rate had fallen to 3 people in 100 by 1998. This period was marked by the gradual introduction of potent anti-HIV therapies known as HAART.
The spectrum of diseases reported in people with HIV has also changed. Whilst opportunistic infections such as CMV retinitis and MAI, which occur at very low CD4 counts, have become less common, non-Hodgkin's lymphoma has increased in frequency from 4% of all ADEs in 1994 to 16% in 1998. This hard-to-treat malignancy has become a significant cause of illness in people with HIV and new therapies are needed.
Data from a large American cohort confirms that mortality following major ADEs has significantly improved since 1995. PCP, CMV, candidiasis, lymphoma and disseminated MAI were all associated with longer survival periods. However, for toxoplasmosis, AIDS dementia and visceral KS survival was unchanged, and in the case of bacterial pneumonia had actually worsened. The reasons for this are unclear - researchers had not so far compared survival rates with individual use of treatments, though this analysis is planned. It is suggested that the poor prognosis associated with bacterial pneumonia may reflect differential access to HAART by injecting drug users, the patient group most commonly affected by this ADE.
Back in Europe, the prevalence of drug resistance mutations poses another challenge. A multicenter study in mainland Europe assessed viral isolates from 415 people with experience of at least two nucleoside analogues taken for at least two months, and from 237 'controls' who had not received more than one.
The frequency of mutations associated with multi-nucleoside and nucleotide resistance was relatively low, at 2.5% for Q151M and 0.5% for T69S-SS. These MDR patterns occurred primarily in people treated with AZT and ddI, or with AZT and ddC.
Worryingly, amongst 112 drug naive samples, 13% had AZT-related mutations (M41L, K70R and/or T215Y/F; this latter mutant results in high-level AZT resistance); 1% ddC mutants (T69D); 1% ddI mutants (L74V); and 6% 3TC mutants (M184V). The prevalence of drug resistance mutations in drug naive patients was 16% overall. This suggests the transmission of drug resistant HIV is becoming a significant public health problem in Europe.
References
Lundgren JD et al. The changing spectrum of AIDS across Europe: 1994-1999. The EuroSIDA study. 39th ICAAC, San Francisco, abstract 1156, 1999.
El-Sadr WM et al. Mortality associated with the occurrence of HIV-related opportunistic diseases (Ods) prior to and since HAART. 39th ICAAC, San Francisco, abstract 1157, 1999.
van Vaerenbergh K et al. Prevalence of nucleoside and multinucleoside drug resistance mutations among European HIV-1 infected patients receiving various combinations of nucleoside analogs. 39th ICAAC, San Francisco, abstract 1170, 1999.