J van Lunzen

Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy

BACKGROUND A subgroup of human immunodeficiency virus type 1 (HIV-1)-infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. METHODS Data analysis from a large multicenter cohort incorporating 14,433 HIV-1-infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/μL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/μL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. RESULTS During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82-90.82; and immune responder group, 24.54; 95% CI, 10.59-48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14-0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09-8.82; P = .03). CONCLUSION Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression.

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study

To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan‐European, observational cohort study.

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

HIV‐infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies.

Does European or non-European origin influence health care and prognosis for HIV patients in Europe?

Background Previous studies, especially in North America, have shown that socio‐economic factors may influence the prognosis for patients with HIV. This study was performed in order to determine if European or non‐European origin influence provision of health‐care and survival among HIV patients in Europe.

Concomitant use of gastric acid-reducing agents is frequent among HIV-1-infected patients receiving protease inhibitor-based highly active antiretroviral therapy*

The aim of the study was to assess the frequency of the concurrent use of gastric acid‐reducing agents among HIV‐1‐infected patients treated with highly active antiretroviral therapy (HAART) combinations.

Hodgkin lymphoma is as common as non-Hodgkin lymphoma in HIV-positive patients with sustained viral suppression and limited immune deficiency: a prospective cohort study

The incidence of HIV‐related non‐Hodgkin lymphoma (NHL) but not that of Hodgkin lymphoma (HL) has been declining. The aim of the study was to compare HIV‐infected patients with NHL and HL with respect to antiretroviral therapy (ART) exposure at the time of lymphoma diagnosis.

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV‐1‐infected individuals

Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips.

Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon

OBJECTIVES The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. METHODS In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. RESULTS At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. CONCLUSIONS Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success.

High HIV prevalence among children presenting for general consultation in rural Cameroon

Data on the HIV-prevalence children presenting to health care facilities in sub-Saharan Africa are scant in general, and the debate about opportunities for paediatric HIV screening is ongoing. Nine hundred and eighty-one children with unknown HIV-status presenting to a large general paediatric outpatient department in rural Cameroon were tested using the Determine HIV-1/2 rapid test (Abbott), and positive results were confirmed with the Hexagon HIV rapid test (Human Diagnostics). In children younger than 18 months, HIV infection was confirmed by PCR testing. Median age was 1.3 years and 52.8% were of male gender. In 514 children below 18 months of age, 16 (3.1%) tested positive. Of those, HIV-1 PCR was available for 11 children, of whom 6 had a positive PCR result. HIV prevalence was highest in the age group 5–9 years, being 8.8%. Malnutrition (33.3 vs 5.2%, p < 0.001) was associated with HIV infection. Our study results indicate that HIV testing should be offered to all children at possible entry points to medical care, irrespective of symptoms, in order to reduce HIV-associated mortality through timely initiation of antiretroviral therapy.

Quality of T-cell responses versus reduction in viral load: results from an exploratory phase II clinical study of Vacc-4x, a therapeutic HIV vaccine

Results For subjects that remained off ART until week 52 (Vacc-4x n=56, placebo n=25), there was a log 0.44 reduction in viral load set point between the Vacc-4x and placebo groups (p=0.0397). There was a similar distribution of HLA class I alleles in the two treatment arms, with the exception of the B35 allele (27% of Vacc-4x subjects versus 8% placebo subjects). The viral load of ELISPOT positive Vacc-4x subjects was significantly lower than that of placebo subjects (p=0.023). There was no significant difference in T-cell proliferation responses between Vacc-4x and placebo groups, however, the percentage of subjects showing proliferative CD4 and CD8 T-cell responses to Vacc-4x peptides increased over time only for the Vacc-4x group. ICS analysis showed a predominance of CD8-mediated T-cell responses to p24 that were significantly increased from baseline for the Vacc-4x group (p 0.05). There was also a trend towards higher numbers of polyfunctional T-cells in the Vacc-4x group compared to the placebo group (p=0.188).