Succinylated Human Serum Albumin (Suc-HSA) for HIV-1 Infection

This is a single centre, single arm study. Subjects will receive 5 consecutive daily doses of Suc-HSA at a dose of 10 mg/kg on days 0, 1, 2, 3 and 4 on the Special Investigation Unit (SIU), with a safety follow up on the SIU for 4 hours on day 1 and 2 hours on the next days. There will be follow-up visits on week 1, 2, 4 and 12. Standard safety parameters (physical examination, clinical symptoms, laboratory hematology and biochemistry) will be followed until week 12. Plasma HIV-1 RNA and CD4+/CD8+ cell counts will be assessed at every visit. Plasma drug levels (trough and peak) will be measured from baseline until week 2.

6 patients will be included in this study as described in this protocol amendment.

Eligible subjects are chronic HIV-1 infected patients who have never been treated with antiretroviral treatment and for whom there is no need to start antiretroviral treatment.

Test Product: Suc-HSA, a candidate HIV-1 fusion inhibitor.

Duration of treatment: 5 days

Criteria for evaluation:

• Safety: symptoms, signs at physical examination, standard hematology and chemistry laboratory parameters- Efficacy: changes in plasma HIV-1 RNA and CD4+ T cell count
• Pharmacokinetics: plasma levels of Suc-HSA: Cmin, Cmax and AUC

Inclusion criteria

• Patient is ≥ 18 years of age;
• Voluntarily signed informed consent;
• Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA);
• Patient is HIV-1 treatment naïve;
• CD4+ T-cell count ≥ 350 x 10^6/L;
• Plasma HIV-1 RNA level at screening visit of at least 5.000 copies/ml, and not varying more than ± 0.5 log10 copies during the preceding 6 month period;
• Patient was participant in part 1 of the original Suc-HSA study (protocol no. 2003-002, version 2.4, dated 18 November 2003) and the administration of Suc-HSA occurred more than 8 weeks ago, OR patient was not participant in this study;
• Patient is one of the following:

• not heterosexually active, OR
• a heterosexually active female, agreeing to use an effective method of contraception with her partner (combined oral contraceptive pill; injectable contraceptive; intrauterine contraceptive device (IUCD); consistent use of condoms if using these; physiological or anatomical sterility in herself or her partner) from 14 days prior to the first administration of study medication until 4 months after the last, and willing to undergo urine pregnancy tests prior to the first and last administration, OR
• a heterosexually active male, agreeing to use an effective method of contraception with his partner from the day of the first administration until 4 months after the last administration.

Exclusion criteria

• History of an AIDS defining event;
• Use of antiretroviral or immunomodulatory therapy;
• Any reason to start antiretroviral therapy at the time of enrolment or which is expected to occur during the course of the study at the time of enrolment;
• Presence of active, replicating hepatitis B and/or C virus co-infection;
• ASAT and/or ALAT > 3 times upper limit of normal (ULN) (AIDS Clinical Trials Group [ACTG] toxicity scale);
• Serum creatinine measuring > 1.5 x ULN;
• Total bilirubin > 2x ULN;
• Neutropenia (absolute neutrophil count < 1000/mm3);
• Presence of any clinically significant disease or findings during screening, that in the opinion of the investigator could compromise the safety of the subject;
• Patient is female and (willing to become) pregnant or breast-feeding;
• Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives.