Development of type 2 diabetes and insulin resistance in people with HIV infection: Prevalence, incidence and associated factors.

BACKGROUND: Diabetes and insulin resistance is an emerging issue in people with HIV. HIV-related mortality and morbidities have decreased markedly over the last few decades, while co-morbidities including type 2 diabetes (T2D) have increased. SETTING: This study investigated the incidence of T2D and insulin resistance in a cohort of HIV-patients on effective treatment. METHODS: Prevalence and baseline predictors of T2D were assessed in a cohort of 570 HIV-positive patients 50 years or older. Patients without diabetes (n = 505) were followed prospectively over a median period of 7.25 year (2012-2020) until T2D development, death or end of the study. T2D was defined as repeated fasting glucose values ≥7.0 mmol/L. Insulin resistance was defined as HOMA-IR ≥3.0. Predictors of T2D development (HIV-related parameters, lipids, hypertension, central obesity, inflammation, smoking and use of statins) were assessed using logistic regression analysis. RESULTS: 30% (153/505) had insulin resistance. During follow up (3485 patient-years) 9% (43/505) developed T2D and 7% (36/505) insulin resistance. Thus, at follow up the prevalence of either T2D or insulin resistance was 46% (232/505). T2D incidence was 1.2/100 patient-years. In multivariate analysis, after adjustment for age, T2D development was associated with baseline insulin resistance, hypertriglyceridemia, central obesity and statin treatment, but no HIV-related factors. CONCLUSION: The incidence of T2D in this cohort of patients with well controlled HIV-infection was high. The predictive factors associated with the development of T2D were not unique for HIV positive patients. The findings underline the importance of lifestyle changes in avoidance of T2D in people with HIV.

Non-AIDS Mortality Is Higher Among Successfully Treated People Living with HIV Compared with Matched HIV-Negative Control Persons: A 15-Year Follow-Up Cohort Study in Sweden.

There is an ongoing debate whether the life span of successfully treated people living with HIV (PLHIV) is comparable with that of the general population. The aim of this cohort study is to compare all-cause mortality between all PLHIV, successfully treated PLHIV, and HIV-negative control persons from the general population and to explore the impact of viral load (VL) at diagnosis. A total of 4066 PLHIV were matched against 8072 HIV-negative controls according to age, sex, and region of birth. Further, associations between VL at diagnosis, time on treatment, treatment outcome, and mortality were assessed over a 15-year period. Cox regression estimates were computed to compare the overall crude and adjusted hazard ratios (HRs) for mortality. After a 15-year follow-up period, successfully treated PLHIV were found to be three times more likely to die when compared with HIV-negative controls (HR 3.01, 95% CI 2.05-4.44, p < 0.001). The risk of mortality decreased from HR 6.02 after the first year of successful treatment. VL >30,000 c/mL at diagnosis was associated with an increased risk of mortality despite long-term antiretroviral therapy (ART) treatment. Although effective viral suppression has led to significant increases in longevity and quality of life, ART has not fully restored life expectancy to a level comparable with that found in HIV-negative persons. Even when PLHIV are successfully treated, there are several other important areas related to death, such as smoking and social factors, where data are still missing.

Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced in patients with a history of symptomatic primary infection.

OBJECTIVE: Epstein-Barr virus (EBV) infection is an established risk factor for B-cell lymphomas in Human Immunodeficiency virus (HIV)-1 infected patients. A disturbed EBV-host relationship is seen in patient groups with a high risk for EBV-associated lymphomas. We have analysed this relationship by measuring EBV-DNA in the blood of HIV-1 carriers. METHOD: EBV-DNA load in B-cells was monitored by PCR in non- or insufficiently antiretroviral treated and rgp160-vaccinated HIV-patients. RESULTS: Both asymptomatic HIV-infected and AIDS-patients showed a 25-40-fold increase in the number of B cell associated EBV-DNA copies compared to healthy controls. Patients included in a vaccine trial with recombinant HIV gp160 showed a 5-fold increase of EBV load compared to non-immunised patients and a 50-fold increase compared to healthy controls. There was no difference whether they received vaccine or "placebo". Vaccinated patients with a history of symptomatic primary HIV-1 infection (PHI) had a 280-fold increase in median EBV load compared to healthy controls, thus suggesting a synergistic effect between the vaccination and PHI, which hypothetically could affect lymphoma risk. CONCLUSIONS: We recommend analysis of EBV-load and long term follow up of lymphoma risk in all therapeutic HIV-1 vaccination trials.

Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara.

BACKGROUND: A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. METHODS: Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-gamma and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs). RESULTS: Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-gamma responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-gamma responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-gamma production was detected in both the CD8(+) T cell compartment (5 of 9 selected vaccinees) and the CD4(+) T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine. CONCLUSION: This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. TRIALS REGISTRATION: International Standard Randomised Controlled Trial number: ISRCTN32604572 .

Autologous cytotoxicity of natural killer cells derived from HIV-infected patients.

NK cells recognize target cells with reduced expression of MHC class I molecules. Human immunodeficiency virus (HIV) infection decreases MHC class I on the cell membrane. The aim of this study was to directly evaluate the role and conditions of NK cell effects in HIV seropositive patients ex vivo. Autologous HIV-infected CD4+ T cells were exposed to NK cells recognition. We discovered an increased lysis of the target cells after infection with human immunodeficiency virus-1 (HIV-1). The expression of the HIV-1 nef gene or the combined expression of nef and tat confers NK susceptibility to autologous CD4+ targets. Downregulation of MHC class I but not HLA-C or CD4 correlated with increased recognition by NK cells. The specific recognition is correlated with downregulation of MHC class I molecules on the infected target cells.

Identification of a unique BK virus variant in the CNS of a patient with AIDS.

Human polyomavirus BK (BKV; GenBank or EMBL or DDBJ accession no. NC001538) is often reactivated in immunosuppressed patients. Reactivation has been associated primarily with excretion of the virus in the urine, and there have been few reports of renal and/or neurological disease caused by BKV in patients with acquired immunodeficiency syndrome (AIDS). Polymerase chain reaction, Southern blotting, and sequencing were used to detect and identify the noncoding control region (NCCR) of BKV in different tissues in an AIDS patient with meningoencephalitis, retinitis, and nephritis. An undescribed reorganized NCCR variant of the virus, completely different from the variants detected in peripheral blood leukocytes (PBLs) and urine, was identified in the cerebrospinal fluid (CSF) and CNS tissues. These results suggest that rearrangements in the NCCR of the virus have resulted in a BKV variant, which is better adapted to the host cell machinery of the cells in CNS tissue. The rearranged variant (BKV CNS) might have been involved in the initiation and/or development of the pathological lesions observed in the CNS-related tissues of this patient.