Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study

OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.     

HIV treatment — a rational approach to the use of antiretroviral agents

Summary. Over the last 2 years, advances in many areas of HIV clinical research and data on the effectiveness of potent combination therapy have substantially influenced the overall perspective of long-term management of HIV disease. However, the progress against HIV also came as a result of the better understanding of HIV pathogenesis. Research work in basic science has contributed considerably to obtain a clearer picture of the mechanisms of HIV infection, mainly through the understanding of key steps in the dynamics and kinetics of viral replication in vivo. Molecular biology also revealed much about the mechanisms of HIV virulence and the emergence of drug resistance. This article will give a short overview of the most recent advances in the field.     

Effects of highly active antiretroviral therapy on vaccine‐induced humoral immunity in HIV‐infected adults

Objectives

The acquisition of adequate vaccine‐induced humoral immunity is especially important in HIV‐infected individuals, who are at increased risk of infections. The aim of the study was to assess the safety of administering a complete vaccination programme to successfully treated HIV‐infected adults and to evaluate specific humoral responses and the effect of highly active antiretroviral therapy (HAART) interruption on these responses.

Methods

A placebo‐controlled, double‐blind clinical trial was designed and 26 HIV‐infected adults enrolled. Study participants were randomized to receive either a complete immunization schedule with commercial vaccines or placebo for 12 months. HAART was then discontinued for 6 months. Specific humoral responses were evaluated at baseline, at month 12 and after HAART interruption and compared between groups.

Results

There were neither local nor systemic secondary effects related to vaccination. Specific humoral responses to vaccines were adequate, but a loss of immunoglobulin G titres was observed after HAART interruption in 12 study participants.

Conclusions

HAART interruption may cause impairment of previously acquired vaccine‐induced immunity in HIV‐infected adults.     

Successful optimization of antiretroviral regimens in treatment‐experienced people living with HIV undergoing liver transplantation

Modern antiretroviral therapy (ART) extends life expectancy for people living with HIV (PLWH). However, most older PLWH (≥50 years) “aged” with HIV and were exposed to historical HIV care practices and older, more toxic ART. In PLWH with exposure to older and multiple ART regimens, the drug interactions between ART frequently used in treatment‐experienced persons and commonly used immunosuppressants remain a significant challenge. However, the advent of newer ART classes (eg, integrase non‐strand transfer inhibitors) and more advanced HIV genetic resistance testing may allow optimization of ART regimens with minimal drug interactions. Here, we present a case series of three PLWH whose complicated ART interacted (or was at risk for interacting) with their post–liver transplant immunosuppression. After a review of their proviral DNA resistance testing, they successfully transitioned onto safer integrase non‐strand transfer inhibitor‐containing ART regimens without viral blips or evidence of organ rejection.     

Association of social stress,illicit drug use,and health beliefs with nonadherence to antiretroviral therapy

OBJECTIVE: To assess the roles of socioeconomic status, social stability, social stress, health beliefs, and illicit drug use with nonadherence to antiretroviral therapy. DESIGN: Cross-sectional study. SETTING: Urban hospital clinic. PARTICIPANTS: One hundred ninety-six consecutive HIV-infected patients taking at least 1 antiretroviral medication, awaiting a visit with their primary care provider. METHODS: Patients were interviewed while waiting for a clinic appointment and were asked to fill out a 4-part survey with questions regarding antiretroviral adherence, illicit drug use, health beliefs, and social situation. Adherence was defined as the percentage of doses taken, i.e., the number of doses taken divided by the number of doses prescribed over a 2-week interval. Univariate and multivariate logistic regressions were performed to identify factors associated with nonadherence in different patient subgroups. MAIN RESULTS: Nonadherence to antiretroviral therapy was associated with active illicit drug use (adjusted odds ratio [AOR], 2.31; 95% confidence interval [95% CI], 1.17 to 4.58), eating fewer than 2 meals per day (AOR, 3.31; 95% CI, 1.11 to 9.92), and feeling as though pressures outside of the clinic affected patient's ability to take antiretroviral medications as prescribed (AOR, 2.22; 95% CI, 0.99 to 4.97). In patients with a history of injection drug use, nonadherence to antiretroviral therapy was independently associated with eating fewer than 2 meals per day (AOR, 17.54; 95% CI, 1.92 to 160.4) and active illicit drug use (AOR, 4.18; 95% CI, 1.68 to 10.75). In patients without any injection drug use, nonadherence was only associated with feeling as though pressures outside of clinic affected patient's ability to take antiretroviral medications as prescribed (AOR, 3.55; 95% CI, 1.07 to 11.76). Male-to-male sexual contact was associated with lower nonadherence in patients with an HIV risk factor other than injection drug use (AOR, 0.35; 95% CI, 0.13 to 0.95). A history of drug use but no illicit drug use within 6 months of the interview was not associated with an increased rate of nonadherence. CONCLUSIONS: Although our sample size was limited and variables that are not significant in subgroup analysis may still be associated with adherence, our results suggest that correlates of nonadherence are HIV risk factor specific. Strategies to increase antiretroviral adherence in HIV-infected patients should include social support interventions targeted at different risk factors for different patient groups.