Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study

Abstract

BackgroundTo examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007.MethodsOutcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes.ResultsAmong patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF.ConclusionsIn this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality.

Antiretroviral changes during the first year of therapy

“…22 In one study, 21 virological failure combined with viral resistance occurred in 24.1% of patients with interruption and resumption of treatment using stavudine (d4T) + 3TC + NVP, d4T + 3TC + EFZ and AZT + 3TC + NVP regimens. Other studies showed that d4T regimens had virological failure in 16.9%, motivated by predictors such as treatment interruptions, use of NVP, initial LTCD 4 < 25 cells/dL, initial VL ≥ 400 copies/mL, and stage of AIDS, 14,16,17,19,20 while only 7.7 and 2.65% obtained treatment failure with the same regimens in other studies. 18,25 These differences may be justified by factors such as ARV classes (NRTI, NNRTI and PI), adherence, toxicity, adverse reactions, incorrect drug combinations in coinfections, and pharmacogenetics of patients.…”

“…14,15,17,[25][26][27] Other studies also reveal that changes in HAART after six months may also occur after confirmation of immuno-virological failure and low adherence. 16,17,[19][20][21] In our population, therapeutic failure, although not the most prevalent cause for HAART replacement, was the reason for switching drugs in 12.6% of the cases that used initial TDF + 3TC + EFZ and AZT + 3TC + EFZ regimens. Other authors showed that TDF + 3TC + EFZ schemes resulted in viral suppression in 92% of patients and virological failure in 8 and 10.8% of patients.…”

“…This finding may signal adhesion problems [19][20][21] or partial immunological reconstitution in patients with low initial LTCD 4 counts. 6,16,20 This situation occurs due to late onset of HAART in immunocompromised patients, so that initially low levels of LTCD 4 are important predictors of the suboptimal recovery response of LTCD 4 . 23,24 Effectiveness of HAART on the decrease in VL from the start of treatment (2 to 4 months) was evidenced, with the majority of patients reaching undetectable levels between the fifth and eighth month.…”

“…13 Studies in Spain, Italy, the United States and India also point to an increasing prevalence of HIV infection among men. [14][15][16][17][18] AIDS was diagnosed in 64.4% of the patients, which can be explained by problems of adherence to HAART and/or late treatment start, according with LTCD 4 count and VL profile, which makes immune reconstitution and viral suppression more difficult with onset of resistance, directly reflecting the appearance of AIDS coinfections and symptoms in 15 to 61% of patients. 7,[19][20][21][22] In the 87 patients studied, LTCD 4 increase was significant between the fifth and eighth month of treatment.…”

Human Immunodeficiency Virus Type 1 Cellular Entry and Exit in the T Lymphocytic and Monocytic Compartments

“…Research and development in HIV-1/AIDS therapy has been focusing on interrupting many steps in HIV-1 life cycle, and the use of current combination antiretroviral therapy (cART) has been relatively successful with respect to controlling the plasma viral load level to below the limits of current assay detection capabilities (Doherty, Ford, Vitoria, Weiler, & Hirnschall, 2013;Gulick et al, 1997;Hammerle, Himmelspach, Dorner, & Falkner, 1997;Hirnschall, Harries, Easterbrook, Doherty, & Ball, 2013;Marconi et al, 2010;Williams, Lima, & Gouws, 2011). One of the cART regiments has included an entry inhibitor, with the inclusion of one of the two current U.S. Food and Drug (FDA)-approved entry inhibitors used in humans either Enfuvirtide or Maraviroc (LaBonte, Lebbos, & Kirkpatrick, 2003;Lieberman-Blum, Fung, & Bandres, 2008;MacArthur & Novak, 2008).…”