Article

Disadvantages of structured treatment interruption persist in patients with multidrug-resistant HIV-1: final results of the CPCRA 064 study.

Department of Medicine, Positive Health Program, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 11/2006; 43(2):169-78. DOI: 10.1097/01.qai.0000242450.74779.ee
Source: PubMed

ABSTRACT We report the final results of Community Programs for Clinical Research on AIDS (CPCRA-064) study, a multicenter, prospective, randomized, controlled trial that determines the long-term clinical impact of structured treatment interruption (STI) in patients with multidrug-resistant (MDR) HIV-1.
Two hundred seventy-four patients on stable antiretroviral therapy with MDR HIV-1 treatment failure were randomized to a 4-month STI, followed by an optimized antiretroviral regimen (STI arm, n = 140) or an immediate change to an optimized antiretroviral regimen (control arm, n = 134). Main outcome measures were progression of disease or death and changes from baseline in HIV RNA levels (log copies/mL) and CD4 cell counts (cells/mm). The median baseline HIV RNA level was 5.0 log copies/mL, the median CD4 count was 147 cells/mm, and the nadir CD4 count was 32 cells/mm. The median follow-up was 37 months. After the STI period, there were no differences in HIV RNA level responses between treatment arms. Differences in CD4 count responses always favored the control arm, with an advantage of 84 cells from 0 to 4 months (P < 0.0001), 50 cells from 4 to 12 months (P < 0.0001), 45 cells from 12 to 24 months (P = 0.006), and 43 cells after 24 months (P = 0.07). Rates in the STI and control arms for first progression-of-disease event or death were 17.5 and 14.3, respectively (hazard ratio = 1.28; P = 0.22).
STI before changing regimens in patients with MDR HIV-1 treatment failure has a prolonged negative impact on CD4 cell count recovery and does not confer progression of disease or virologic benefits.

0 Followers
 · 
122 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Both antiretroviral treatment interruption (TI) and cessation have been strongly discouraged since 2006. We describe the incidence, duration, and risk factors for TI and loss-to-follow-up (LTFU) rates across 13 countries. All 4689 adults (76% men) in two large HIV cohorts in Australia and Asia commencing combination antiretroviral therapy (ART) to March 2010 were included. TI was defined by ART cessation >30 days, then recommencement, and loss to follow-up (LTFU) by no visit since 31 March 2009 and no record of death. Survival analysis and Poisson regression methods were used. With median follow-up of 4.4 years [interquartile range (IQR):2.1-6.5], TI incidence was 6.7 per 100 person years (PY) (95% CI:6.1-7.3) pre-2006, falling to 2.0 (95% CI:1.7-2.2) from 2006 (p<0.01). LTFU incidence was 3.5 per 100 PY (95% CI:3.1-3.9) pre-2006, and 4.1 (95% CI:3.5-4.9) from 2006 (p=0.22). TIs accounted for 6.4% of potential time on ART pre-2006 and 1.2% from 2006 (p<0.01), and LTFU 4.7% of potential time on ART pre-2006 and 6.6% from 2006 (p<0.01). Median TI duration was 163 (IQR: 75-391) days pre-2006 and 118 (IQR: 67-270) days from 2006 (p<0.01). Independent risk factors for the first TI were: Australia HIV Observational Database participation; ART initiation pre-2006; ART regimens including stavudine and didanosine; three nucleoside analogue reverse transcriptase inhibitors; ≥7 pills per day; and ART with food restrictions (fasting or with food). In conclusion, since 2006, 7.8% of patients had significant time off treatment, which has the potential to compromise any 'test and treat' policy as during the interruption viral load will rebound and increase the risk of transmission.
    AIDS patient care and STDs 12/2013; DOI:10.1089/apc.2012.0439 · 3.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the early years of the highly active antiretroviral therapy (HAART) era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR) HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost. Starting in 2006, data began to emerge supporting the use of new drugs from the original antiretroviral classes (tipranavir, darunavir, and etravirine) and drugs from new classes (raltegravir and maraviroc) for the treatment of MDR HIV. Their availability has enabled patients with MDR HIV to achieve full and durable viral suppression with more compact and cost-effective regimens including at least two and often three fully active agents. The emergence of drug-resistant HIV is expected to continue to become less frequent in the future, driven by improvements in the convenience, tolerability, efficacy, and durability of first-line HAART regimens. To continue this trend, the optimal rollout of HAART in both rich and resource-limited settings will require careful planning and strategic use of antiretroviral drugs and monitoring technologies.
    AIDS research and treatment 11/2012; 2012:595762. DOI:10.1155/2012/595762