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Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study.

Meintjes G, Dunn L, Coetsee M, Hislop M, Leisegang R, Regensberg L, Maartens G - AIDS Res Ther (2015)

Bottom Line: For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014. 152 patients were included.By the end of the study 17 (11.2 %) of the patients had died.The KM estimate of cumulative survival was 87.2 % at 2000 days.

View Article: PubMed Central - PubMed

Affiliation: Clinical Infectious Diseases Research Initiative (CIDRI), Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925 South Africa ; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa ; Department of Medicine, Imperial College London, London, UK.

ABSTRACT

Background: An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.

Methods: Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.

Results: 152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.

Conclusions: Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.

No MeSH data available.


Related in: MedlinePlus

CD4 count prior to start of salvage ART and at 6 months intervals on salvage ART. The graph shows the median and interquartile range for CD4 counts (for those patients who had CD4 count performed) prior to starting ART salvage, then at 6 months intervals on salvage ART (with a ±3 month window for each 6 month interval)
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Fig2: CD4 count prior to start of salvage ART and at 6 months intervals on salvage ART. The graph shows the median and interquartile range for CD4 counts (for those patients who had CD4 count performed) prior to starting ART salvage, then at 6 months intervals on salvage ART (with a ±3 month window for each 6 month interval)

Mentions: The cumulative incidence of virologic rebound after suppression was 19 and 13.9 % of those suppressing to VL ≤400 and ≤50 copies/ml respectively. The median CD4 count increased from 153 to 448 cells/mm3 by 3 years on salvage ART (Fig. 2). The KM estimate of cumulative survival was 87.2 % at 2000 days (Fig. 1c). One patient stopped ritonavir of their own accord due to gastro-intestinal side effects. There were no other interruptions or substitutions for intolerance or toxicity.Fig. 2


Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study.

Meintjes G, Dunn L, Coetsee M, Hislop M, Leisegang R, Regensberg L, Maartens G - AIDS Res Ther (2015)

CD4 count prior to start of salvage ART and at 6 months intervals on salvage ART. The graph shows the median and interquartile range for CD4 counts (for those patients who had CD4 count performed) prior to starting ART salvage, then at 6 months intervals on salvage ART (with a ±3 month window for each 6 month interval)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666151&req=5

Fig2: CD4 count prior to start of salvage ART and at 6 months intervals on salvage ART. The graph shows the median and interquartile range for CD4 counts (for those patients who had CD4 count performed) prior to starting ART salvage, then at 6 months intervals on salvage ART (with a ±3 month window for each 6 month interval)
Mentions: The cumulative incidence of virologic rebound after suppression was 19 and 13.9 % of those suppressing to VL ≤400 and ≤50 copies/ml respectively. The median CD4 count increased from 153 to 448 cells/mm3 by 3 years on salvage ART (Fig. 2). The KM estimate of cumulative survival was 87.2 % at 2000 days (Fig. 1c). One patient stopped ritonavir of their own accord due to gastro-intestinal side effects. There were no other interruptions or substitutions for intolerance or toxicity.Fig. 2

Bottom Line: For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014. 152 patients were included.By the end of the study 17 (11.2 %) of the patients had died.The KM estimate of cumulative survival was 87.2 % at 2000 days.

View Article: PubMed Central - PubMed

Affiliation: Clinical Infectious Diseases Research Initiative (CIDRI), Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925 South Africa ; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa ; Department of Medicine, Imperial College London, London, UK.

ABSTRACT

Background: An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.

Methods: Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.

Results: 152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.

Conclusions: Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.

No MeSH data available.


Related in: MedlinePlus