Risk of high‐level viraemia in HIV‐infected patients on successful antiretroviral treatment for more than 6 months

Objectives

According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.

Methods

A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.

Results

We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.

Conclusion

The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low.     

Effect of simplification from protease inhibitors to boosted atazanavir‐based regimens in real‐life conditions

Background

Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well‐tolerated, once‐daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs.

Objective

The aim of the study was to determine the effectiveness and safety of ATV‐containing regimens in patients who have simplified their antiretroviral treatment.

Methods

SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI‐containing therapy and who were switched to an ATV/r‐based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction.

Results

A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/μL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low‐density lipoprotein cholesterol were ?13 mg/dL (?7%; P<0.0001), ?19 mg/dL (?13%; P<0.0001) and ?7 mg/dL (?6%; P=0.021), respectively.

Conclusions

In a real‐world setting, switching from other PIs to ATV/r is a well‐tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Long‐term (96‐week) follow‐up of antiretroviral‐naïve HIV‐infected patients treated with first‐line lopinavir/ritonavir monotherapy in the MONARK trial*

Background

The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral‐naïve patients.

Methods

A total of 136 antiretroviral‐naïve patients, with a CD4 cell count above 100 cells/μL and a plasma HIV RNA below 100 000 HIV‐1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n=83) or lopinavir/ritonavir+zidovudine/lamivudine (n=53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent‐to‐treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n=83), and then focused on patients who had an HIV RNA <50 copies/mL at week 48 (n=56).

Results

At week 96, 39 of 83 patients (47%) had HIV RNA <50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA >400 copies/mL. Focusing on the 56 patients with an HIV RNA <50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA <50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI‐associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96.

Conclusion

By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA <50 copies/mL at week 96. The occurrence in some patients of low‐level viraemia (50–500 copies/mL) may increase the risk of drug resistance. First‐line lopinavir/ritonavir monotherapy cannot be systematically recommended.     

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.     

British HIV Association (BHIVA) national cohort outcomes audit of patients commencing antiretrovirals from naïve

Objectives

The aim of this work was to audit the extent to which routine HIV care in the UK conforms with British HIV Association (BHIVA) guidelines and specifically the proportion of patients starting highly active antiretroviral therapy (HAART) who achieve the outcome of virological suppression below 50 HIV‐1 RNA copies/mL within 6 months.

Methods

A prospective cohort review of adults with HIV infection who started antiretroviral therapy (ART) for the first time between April and September 2006 was carried out using structured questionnaire forms.

Results

A total of 1170 adults from 122 clinical sites participated in the review. Of these patients, 699 (59.7%) started ART at CD4 counts <200 cells/μL and 193 (16.5%) had not been tested for HIV drug resistance. Excluding patients with valid reasons for stopping short‐term ART, 795 (73.5%) of 1081 patients had an undetectable viral load (VL) at follow‐up. Detectable VL was strongly associated with pretreatment CD4 count below 50 cells/μL and pretreatment VL above 100 000 copies/mL, and was not associated with clinic location or case load. About a quarter of patients did not have a VL measurement during the first 6 weeks after starting ART.

Conclusions

The majority of patients who initiated ART at sites participating in this UK national audit were managed within the BHIVA guidelines and achieved virological suppression below 50 copies/mL around 6 months after commencing treatment. Poor VL outcomes were associated with very low CD4 cell count and/or high VL at baseline but not with clinic case load or location. There is an urgent need to diagnose patients at an earlier stage of their HIV disease.