Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.

The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate.

Self-reported adherence to antiretroviral treatment and degree of sense of coherence in a group of HIV-infected patients.

The goal of this study was to explore the relation between self-reported adherence to antiretroviral treatment and degree of sense of coherence in a group of human immunodeficiency virus (HIV)-infected patients. Ninety-nine patients from an outpatient clinic, all undergoing antiretroviral therapy, participated. Questionnaires were answered twice at a 12-month interval. The 29-item Sense of Coherence (SOC) Scale was used for measuring the ability to cope with stressful life situations. Medication adherence was assessed with self-reported measurements. Clinical characteristics and background variables were collected from the medical records. Results from variables measured with the 12-month interval show a significant concordance with disease stage (p < or = 0.0001), and in HIV-RNA copies per milliliter (p < or = 0.0001) and an increase in CD4 cell count/mm3 (p = < 0.0001). Univariate analysis showed significant differences between nonadherent patients (n = 19) and adherent patients (n = 80) at the last measurement (i.e., the nonadherent group had lower CD4 cell count/mm3 [p = 0.004], higher HIV-1 RNA levels [p 50.029], and lower SOC [p = 0.04] than the adherent group). Finally, multiple regression analyses showed that at measurement 2 the SOC predicted nonadherence, the lower SOC the more missed doses (p < or = 0.01). Because SOC seems to play an important role in this group of patients managing their disease, a caring patient-provider relationship should be developed to minimize nonadherent behaviour. For this reason SOC scale might be of great clinical value to identify patients needing the most support for successful treatment.

Health-related quality of life in relation to sense of coherence in a Swedish group of HIV-infected patients over a two-year follow-up.

The purpose of the present study was to describe HIV-infected patients' self-reported health-related quality of life (HRQOL) in relation to sense of coherence over a 24-month period. A total of 104 HIV-infected patients (71% males) answered questionnaires at three times at 12-month intervals. At the same time, clinical characteristics were collected from the patients' medical records. HRQOL was measured by the HIV-symptom scale, the Health Index, and the Well-Being Scale. Coping ability was measured with the 29-item sense of coherence (SOC) scale. The patients were divided into three groups depending on SOC scores (low, moderate, high). The results indicate that the group with low SOC scores rate their HRQOL worse than the other groups at all three measurements (p values from <0.05 to <0.001). Over the 2-year period, the patients' CD4 cell count=mm3 increased significantly (p values <0.001), indicating good response to antiretroviral treatment. However, their HRQOL did not improve during these 2 years. Patients with higher SOC rate their HRQOL better than those with a lower SOC, during these years. Future studies should investigate the predictive value of the SOC scale of HRQOL in HIV-infected patients.

Children born to HIV-1-infected women in Sweden in 1982-2003: trends in epidemiology and vertical transmission.

To describe the HIV-1 epidemic among childbearing women and their children in Sweden, a population-based analysis of data on all known mother-child pairs in Sweden with perinatal exposure to HIV-1 1982-2003 was conducted. The mother-to-child transmission (MTCT) rate in children prospectively followed from birth decreased from 24.7% in 1985-1993 to 5.7% in 1994-1998 and 0.6% in 1999-2003. The use of antiretroviral treatment of the mother during pregnancy and/or prophylactic antiretroviral intervention increased from 2.3% to 91.6% during the same period, and the elective cesarean delivery rate increased from 8.0% to 80.3%. No MTCT of HIV-1 occurred in Sweden after 1999.Fifty-one vertically HIV-1-infected children aged 2.7 to 17.6 years were living in Sweden by 31 December 2003, 71% being treated with antiretroviral agents. No HIV-1-related child death has been reported in Sweden after 1996. The conclusion is that MTCT of HIV-1 can be almost eliminated when appropriate resources are available. A national pregnancy screening program for HIV-1 running since 1987 with a high acceptance rate and the implementation of measures to prevent MTCT since 1994 have resulted in a significant decrease in the number of infected children. Inasmuch as knowledge of the infection status of the mother is crucial for reduction in MTCT of HIV-1, continued antenatal screening is important even in a low-prevalence country such as Sweden.

Therapeutic immunization for HIV.

Vaccines have entered into human clinical trials against infectious diseases and as therapies against cancer. The HIV virus establishes a latent infection at a very early stage and the T cell memory of the infected patient is rapidly destroyed. However, results of immunotherapy after DNA and protein immunization show that vaccine-induced immune responses might be present for a long period of time. Patients subjected to therapeutic immunization appear to do well, and to have a small immunological advantage, which, however, will have to be improved. The vaccine therapy should start early, while adequate reservoirs of appropriate T helper cells are available and still inducible. The DNA vaccines induce a relatively long-lived immunological memory, and gene-based immunization is effective in inducing cytotoxic CD8(+) T cells and CD4+ helper cells. Protein vaccines, on the other hand, primarily give T cell help. It thus appears that DNA and protein approaches to HIV immunization complement each other. A surprisingly broad reactivity to peptides from different subtypes of HIV was identified in individuals infected with several subtypes of HIV.

Persistence of earlier HIV-1 drug resistance mutations at new treatment failure.

The objective was to study the persistence of drug resistance mutations detected earlier at virological failure during second or third line antiretroviral therapy. Therefore, in HIV-1 infected patients, with a virological treatment failure, genotypic resistance testing was carried out before change of therapy and at the next treatment failure. The majority of primary and secondary resistance mutations persisted in both the reverse transcriptase (RT) and the protease genes. After changing from zidovudine- to stavudine-containing regimens, the thymidine analogue mutations (especially M41L and T215Y/F) were found at new treatment failure in almost all patients. The M184V mutation disappeared in most (64%) non-3TC treated patients, although it persisted in a few didanosine- and abacavir-treated subjects. The primary protease inhibitor (PI) mutations reverted back to wild type in most patients who did not receive a new PI. In contrast, after changing from indinavir to saquinavir or nelfinavir, the M46I/L and/or V82A/F/ST disappeared in only 9 of 21 occasions at the new treatment failure. Most secondary mutations persisted with the exception of N88D. In patients with multiple treatment failures, most NRTI mutations thus persist frequently at new failures with modified treatment. A similar pattern is seen for protease inhibitors. The data suggest that clinical cross-resistance may develop via common pathways within all categories of drugs in heavily treated patients.

Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child.

Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1) isolates of various subtypes from 11 women during pregnancy and their infected children. Isolates from peripheral blood mononuclear cells (n=79) and from plasma (n=59) were available. The clinical and immunological stages of HIV-1 infection were recorded. Coreceptor use was tested on human cell lines expressing CD4 and different chemokine receptors. The R5 virus predominated, and only 9 isolates from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child no. 9) and age 48 months (child no. 10), whereas no children followed up to a similar age whose mothers were carrying the R5 virus experienced such a switch (P=.048). This points to a link between the presence of X4 virus in the mother and the emergence of X4 virus in her child.