Second-line combination antiretroviral therapy in resource-limited settings: Facing the challenges through clinical research

National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW 2010, Australia.
AIDS (Impact Factor: 5.55). 08/2007; 21 Suppl 4(Suppl 4):S55-63. DOI: 10.1097/01.aids.0000279707.01557.b2
Source: PubMed


Combination antiretroviral therapy (ART) has dramatically altered the prognosis of individuals infected with HIV. In the past 5 years there has been a concerted effort to increase access to ART in the developing world. The evidence to date suggests that adherence to therapy and clinical outcomes in developing world programmes are at least the equal of those observed in developed countries. Although access to first-line therapy is reasonably well established, there is a substantial and unacceptable mortality rate in the first 6 months after initiation of ART, particularly in those with low CD4 cell counts and late-stage disease. Failure of first-line ART is inevitable in a proportion of patients. Access to second-line ART regimens in developing countries is problematic, mainly because of the expense of HIV protease inhibitors (PIs). Access to second-line ART may be facilitated by novel strategies using the existing recommended agents or by the use of new agents or classes. Refinement of programmes in the developing world must be underpinned by the same rigorous scientific research effort that has characterized the success of the effort in the developed world. Therefore, the funding bodies responsible for the roll-out of antiretroviral access across the globe must mandate, incorporate and fund clinical research as an intrinsic aspect of combination ART roll-out programmes.

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    • "However, because of the limits imposed by first-line regimen options (limited number of available drugs, including a thymidine analog) and because some second-line drugs are either poorly available or prohibitively expensive, the choice of second-line strategies becomes an important and difficult issue for both the patients and national programmes [19]. Few data on the feasibility and efficacy of such second-line regimens in resource-limited settings have been published so far [20-24]. "
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    ABSTRACT: The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia. Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm. Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³ and the median viral load was 4.7 Log10. Second-line regimens prescribed were ddI/3TC/LPV/r (65.7%), ddI/TDF/LPV/r (10.0%), ddI/AZT/LPV/r (8.6%) and TDF/3TC/LPV/r (7.1%). The median CD4 T cell gain was +258 cells/mm³ at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis. These data suggest that a LPV/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.
    Journal of the International AIDS Society 03/2011; 14:14. DOI:10.1186/1758-2652-14-14 · 5.09 Impact Factor
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    • "More recently, Mocroft et al [8] also reported that CD4 did not significantly decrease even HIV VL exceeded 10 000 copies/mL in patients treated with regimen containing a boosted protease inhibitor. The issue of when to switch from first line regimens may therefore be difficult, especially for patients with modest, stable HIV VL who are clinically doing well [5,9]. "
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    ABSTRACT: The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20,000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5,000, 4,000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.
    BMC Infectious Diseases 12/2010; 10(1):361. DOI:10.1186/1471-2334-10-361 · 2.61 Impact Factor
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    • "In adults on ART, most deaths occur within the first 3 months of treatment (Zachariah et al. 2006; Libamba et al. 2007). Children have been thought to follow similar trends (Bolton-Moore et al. 2007; Boyd & Cooper 2007; Callens et al. 2009). Most deaths occurred within the first 100 days on treatment, particularly among the youngest patients. "
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    ABSTRACT: To determine predictors of mortality in children on anti-retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi. Retrospective case cohort study by chart review of children who had started ART between October 2004 and May 2006. Bivariable and multivariable analysis were performed with and without defaulters to evaluate associations according to vital status and to identify independent predictors of mortality. Forty-one of 258 children (15.9%) were deceased, 185 (71.7%) were alive, and 32 (12.4%) had defaulted: 51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age. Most were WHO stage III or IV (56% and 37%, respectively). On multivariate analysis, factors most strongly associated with mortality and defaulting were age <18 months [hazards ratio (HR) 2.11 (95% CI 1.0-4.51)] and WHO stage IV [HR 2.00 (95% CI 1.07-3.76)]. To improve outcomes of HIV-positive children, they must be identified and treated early, specifically children under 18 months of age. Access to infant diagnostic procedures must be improved to allow effective initiation of ART in infants at higher risk of death.
    Tropical Medicine & International Health 07/2009; 14(8):862-9. DOI:10.1111/j.1365-3156.2009.02315.x · 2.33 Impact Factor
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