HIV This Week

Grabar S, Lanoy E, Allavena C, Mary-Krause M, Bentata M, Fischer P, Mahamat A, Rabaud C, Costagliola D; on behalf of the Clinical Epidemiology Group of the French Hospital Database on HIV. Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy. HIV Med. 2008;(4):246-256.

Grabar and colleagues aimed to analyse the impact of combined antiretroviral treatment on survival with AIDS, according to the nature of the first AIDS-defining clinical illness; and to examine trends in AIDS-defining causes and non-AIDS-defining causes of death. From the French Hospital Database on HIV, they studied trends in the nature of the first AIDS-defining clinical illness and subsequent survival in France during three calendar periods: the pre-combined antiretroviral treatment period (1993-1995; 8027 patients), the early combined antiretroviral treatment period (1998-2000; 3504 patients) and the late combined antiretroviral treatment period (2001-2003; 2936 patients). In the pre-combined antiretroviral treatment period the three most frequent initial AIDS-defining clinical illnesses were Pneumocystis carinii (jirovecii) pneumonia (15.6%), oesophageal candidiasis (14.3%) and Kaposi’s sarcoma (13.9%). In the late combined antiretroviral treatment period, the most frequent AIDS-defining clinical illness were tuberculosis (22.7%), Pneumocystis carinii (jirovecii) pneumonia (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first AIDS-defining clinical illness fell significantly after the arrival of combined antiretroviral treatment. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma, and Mycobacterium avium complex infection. After an AIDS-defining clinical illness, the 3-year risk of death from an AIDS-defining cause fell fivefold between the pre-combined antiretroviral treatment and late combined antiretroviral treatment periods (39%vs. 8%), and fell twofold for non-AIDS-defining causes (17%vs. 9%). The cuthors conclude that the relative frequencies of initial AIDS-defining clinical illness have changed since the advent of combined antiretroviral treatment. Tuberculosis is now the most frequent initial AIDS-defining clinical illness in France; this is probably the result of the increasing proportion of migrants from sub-Saharan Africa. After a first AIDS-defining clinical illness, combined antiretroviral treatment has a major impact on AIDS-defining causes and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar.

Editors’ note: Monitoring the evolution in initial AIDS-defining illnesses with the introduction of antiretroviral treatment and changing patient demographics, such has been done in France, is useful for adapting services to new disease and patient profiles. The dramatic reductions in mortality in France reflect the transformation of AIDS into a chronic, manageable disease for the majority of patients in this high-income country.

Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs. Steigbigel and colleagues conducted two identical trials in different geographic regions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that had triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio. In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting non-completion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per millilitre, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per millilitre was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups. The authors conclude that in HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)

Editors’ note: Integrase is a viral enzyme that catalyzes the insertion of proviral DNA into the host-cell genome. Even when HIV strains are resistant to other classes of antiretroviral drugs, the distinct mechanism of action of integrase inhibitors, in combination with optimized background therapy, can reduce viral load and increase CD4 counts, as shown in this study of patients with triple-class drug resistance.