Characteristics and Outcome of a Cohort of HIV-1 Non-B Subtype–Infected Patients After a 10-Year Follow-up Period: A Single Centre Experience
Subtype B has for many years accounted for most HIV-1 infections in Europe and the United States;1 however, non-B subtypes are responsible for most infections worldwide and they have recently spread throughout Europe. Moreover, there are discordant data about virological outcome of patients harboring HIV-1 non-B subtypes. In fact, Häggblom et al2 recently suggested an increased risk of virological failure in patients with HIV-1 subtype C, especially if a boosted protease inhibitor (PI)-based regimen was prescribed. Previously, a large cohort analysis showed a worse prognosis in HIV-1 subtype A infected patients.3 By contrast, data from large cohorts demonstrated similar virological and immunologic responses to combined-antiretroviral therapy (cART) in different subtypes.4 The aim of our report was to retrospectively observe characteristics and virological failure rate of patients harboring HIV-1 non-B subtypes in a monocentric cohort after a 10-year follow-up period.
We retrospectively analyzed data of all HIV-positive cART-naive patients who underwent genotypic resistance testing in our Outpatient Clinic between March 1, 2000 and September 30, 2005 and started cART. A database was generated by merging the clinical data of the Department of Infectious and Tropical Diseases and the HIV-1 genotypic data of the Institute of Microbiology of the University of Brescia. Subtyping was obtained using the REGA HIV subtyping tool (available at http://www.bioafrica.net/subtypetool/html/) associating the phylogenetic analysis and bootscan method.5 Prevalence of non-B subtype viruses was calculated and virological failure rate was evaluated after a 10-year follow-up period. Virological failure was defined as plasma HIV viral load above 1000 copies per milliliter based on 2 consecutive viral load measurements after 3 months, with adherence support. Blips were defined as an isolated detectable HIV RNA level (>50 copies/mL) followed by a return to virological suppression.
Study population included 228 HIV-infected patients: 42 (18.4%) harbored a non-B subtype. The most frequent non-B subtypes were AG (14/42, 33.3%) and F1 (11/42, 26.2%). The remaining patients harbored the following subtypes: G (4/42, 9.5%), A-E (3/42, 7.1%), C (3/42, 7.1%), B-F (2/42, 4.8%) and 18-cpxAG, A-G-IBNG, BF-1, cpxAFG, D (1/42 patient each, 2.4%). Most of patients harboring non-B subtypes were from Italy (20/42, 47.6% vs 158/186, 84.9% of B subtypes) and from Africa (20/42, 47.6% vs 7/186, 3.7% of B subtypes). Ten-year follow-up data are available for 168 (73.7%) patients, 137/186 (73.6%) harboring B subtype and 31/42 (73.8%) harboring non-B subtypes. Rate of virological failure and blips are shown in Table 1, and cART regimens. Rate of virological failure and blips did not differ in patients harboring B and non-B subtypes (P = 0.561 and P = 1, respectively; χ2 test). cART regimen at failure was nonnucleoside reverse transcriptase inhibitor (efavirenz, EFV)-based for patients harboring B-subtype and PI (atazanavir/ritonavir)-based for one non-B patient who faced virological failure (G subtype). Patient no. 1 and no. 2 (B subtype) were on treatment with EFV, didanosine, and tenofovir (TDF); genotypic resistance testing at failure showed high-level resistance to drugs with nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance mutations. Patient no. 3 (B subtype) was treated with EFV + emtricitabine (FTC)/TDF and presented high-level resistance to EFV and FTC at failure. Patient no. 4 (G subtype) was on treatment with atazanavir/ritonavir, TDF, and FTC. However, no resistance mutations were shown at genotypic resistance testing at failure that was probably only attributable to scarce compliance. Mean time to failure was 26 months (SD 32 months). 1/1 non-B patient presented blips before failure (on the same cART regimen), whereas 0/3 B-subtype patients faced blips before failure.
HIV epidemics are rapidly evolving in Europe, because of the large migration phenomena, with the emergence of different HIV-1 non-B subtypes.