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Excerpt
The patients had median CD4 cell counts of 405 cells/ml (range 142–693). They were counselled on the use of contraceptives and the fecundity status of the female patient was monitored. The plasma viral load was determined using a Roche Ultrasensitive Kit (Roche Diagnostics, Lewes, East Sussex, UK) with a detection limit of 50 HIV-1 copies/ml. The majority of the patients had a baseline plasma HIV-1 viral load of less than 50 copies/ml with one patient (P.W.) having more than 1000 copies/ml (Table 1). They were evaluated at baseline (−4 weeks), 1, 2, 4, 6 and 8 weeks of thalidomide and at week 4 of a drug-free follow-up period. Plasma thalidomide levels were determined [5] and correlated with the viral load at weeks 4 and 8 and at the follow-up visit. For statistical analysis, viral loads below the detection limit were taken as 50 copies/ml, and when necessary, data were log-transformed before applying a paired t-test.
Thalidomide was generally well tolerated, but two patients failed to complete the study after complaining of excessive fatigue (patient L.H.) at week 1 and a ‘spaced out’ feeling (patient S.A.) at week 6.
Viral load was variable but a general trend was discernible. An approximately twofold increase (range 1.0–4.3; P < 0.05) in the plasma HIV-1 viral load was seen at week 2, which returned to baseline by week 4 on continued thalidomide treatment (Table 1). One subject (M.F.) showed an additional late increase in viral load at week 8 before declining at the follow-up visit. The median plasma concentrations of thalidomide were 313 ng/ml at week 4 and 162 ng/ml at week 8 in samples taken nominally at more than 10 h post-dose. Bodyweight increased by (mean with range) 1.9 kg (0.6–3.2, week 1; P < 0.05); 1.9 kg (1.0–3.1, week 2, P < 0.05); 1.3 kg (−1.8–3.4, week 4); 2.1 kg (−1.0–4.2, week 6) and 3.1 kg (1.6–5.2, week 8; P < 0.05) compared with baseline. Five out of the seven subjects continued to show a net weight gain, ranging from 0.7 to 3.3 kg whereas the remaining two subjects showed net weight losses of 0.1 and 1.6 kg at the follow-up visit. Subsequent expanded studies using 64 patients confirmed our finding of significant weight gains [6].
The beneficial effects of thalidomide in promoting weight gain in HIV-associated cachexia have been tempered by concerns about the accompanying increase in viral load [2–4]. In the present study, consistent weight gain was apparent after one week and a temporary increase in the plasma HIV-1 viral load after 2 weeks of thalidomide treatment, even with highly active antiretroviral therapy. The weight gain was maintained but the viral load declined to baseline levels on continued treatment with thalidomide. One subject (M.F.), however, had an additional late increase in plasma viral load at week 8.
