Italian investigators have found evidence
of worsening glucose tolerance in highly treatment-experienced HIV-positive
patients treated with nucleoside-sparing regimens. The small study, which is
published in the online edition of AIDS,
monitored the glucose metabolism of 39 patients over three years.
“The drugs included in these regimens have
not been specifically associated with worsening of glucose metabolism,” note
the authors.
The patients were treated with two
alternative combinations: raltegravir (Isentress),
etravirine (Intelence) plus maraviroc
(Celsentri); or raltegravir,
etravirine with ritonavir-boosted darunavir (Prezista). A total of fifteenth patients (39%) were treated with
the maraviroc-containing regimen and 61% received the darunavir/ritonavir-based
therapy. All were highly treatment experienced and were switched to these
regimens because of virological failure.
The patients had normal fasting glucose
levels (below 110 mg/dl) when they switched therapy. Fasting glucose and
insulin levels were monitored every three months over three years of treatment.
Impaired glucose tolerance was defined as a glucose level above 140 mg/dl, and
diabetes as a basal glucose level of 126 mg/dl or a two-hour post-load level of
200 mg/dl.
The patients had an average age of 48 and 84%
were men. They had extensive experience of treatment, the average duration
being 16 years. All achieved an undetectable viral load after switching
treatment, which was also associated with robust increase in CD4 cell counts.
After 156 weeks of treatment, fasting
glucose levels had increased significantly (overall, p = 0.002; maraviroc-based
treatment, p = 0.007; darunavir/ritonavir-containing therapy, p = 0.029).
Insulin levels had also decreased in the
darunavir/ritonavir group (p = 0.027).
Impaired glucose tolerance was observed in
three patients (8%) and diabetes was diagnosed in five (13%), four of whom were
taking maraviroc.
The investigators were surprised by this
finding as maraviroc has been
“postulated to have a protective effect on at least type-1 DM.”
Older age was the only significant risk
factor for the development of impaired glucose tolerance or diabetes (p =
0.003).
However, the investigators also noted there
was a significant relationship between increases in CD4 cell count and fasting
insulin levels at week 156 (p = 0.018). There was also a relationship which
bordered on significance between increase in waist circumference and the
development of insulin resistance (p = 0.051).
They therefore conclude that the worsening
glucose metabolism observed in their patients “may be a consequence of both
antiretroviral drugs and restoration of health.”
