A Trial to Confirm a Sustained Virological Suppression Defined as HIV-RNA <50 Copies/ml of 3 Different Doses of Fozivudine in Context to a Standard Zidovudine Based Antiretroviral Therapy Regimen (FATI-01)

• Proportion of patients with plasma HIV RNA < 50 copies/ml [ Time Frame: at week 24 ] [ Designated as safety issue: No ]
  

• Proportion of patients with plasma HIV RNA <50 copies/ml [ Time Frame: at week 8 and 12 ] [ Designated as safety issue: No ]
  
• Proportion of patients with plasma HIV RNA < 400 copies/ml [ Time Frame: at week 8, 12 and 24 ] [ Designated as safety issue: No ]
  
• Mean HIV log10 reduction compared to baseline [ Time Frame: at week 2, 4 and 8 ] [ Designated as safety issue: No ]
  
• Variation of circulating total lymphocyte count [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]
  
• Variation of circulating CD4+ lymphocyte count [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]
  
• Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) before and after the first dose [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  Various pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) will be assessed before the first treatment and during the course of 12 hours after the first treatment.
  
  
• Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) at steady state [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  Various pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) will be assessed during the course of 12 hours after 4 weeks of treatment.
  
  
• Proportion of clinical events stage 3 or 4 of WHO HIV classification [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
  
• Number of participants with Adverse Events as Measure of safety and tolerability [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
  The number of Adverse Events and also the quality, severity and relatedness to study drug are documented and analysed.
  
  
• Incidence of resistance mutations after confirmed treatment failure (confirmed HIV RNA > 1000 copies/ml [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  

The study will evaluate four different oral 1st line antiretroviral regimens: three study arms will contain different doses of Fozivudine (FZD) plus Lamivudine (3TC) in a twice daily or once daily application plus once daily Efavirenz. The 4th study arm will contain standard Zidovudine (AZT)/Lamivudine (3TC) twice daily in a fixed dose combination plus once daily Efavirenz. The treatment duration will be 24 weeks.

In a pharmacokinetic Sub-Study Pharmacokinetic (PK) characteristics will be determined under controlled conditions in a sub population to evaluate PK values of the study drugs.

Primary Objective

The primary objective is to confirm a sustained virological suppression (HIV RNA <50 copies/ml) after 24 weeks of treatment between three different doses of Fozivudine (FZD) based antiretroviral 1st line treatment regimen in context to a standard Zidovudine (ZDV) based treatment regimen in non subtype B HIV-1 infected individuals from Africa.

Secondary Objectives

1. HIV-RNA log10 reduction of HIV-RNA at 2, 4 and 8 weeks of treatment between different arms
2. Virological response (HIV RNA <50 copies/ml) at 8 and 12 weeks of treatment between different arms
3. Virological response (HIV RNA <400 copies/ml) at 8, 12 and 24 weeks of treatment between different arms
4. Immunologic response: variation in CD4 lymphocytes between different arms
5. Drug toxicity, particularly anaemia, neutropenia and gastrointestinal adverse events
6. Resistance pattern for in patients with virological failure
7. Clinical trial capacity building of African study sites within the FATI network
8. Establishment of a Fozivudine Drug developing consortium (NET) including members of pharmaceutical manufacturers in Asia, Africa and Europe.
9. Development and piloting of a capacity development monitoring and evaluation framework

Pharmacological Objectives

1. Pharmacokinetic assessments after the first intake of study drugs in a subset of study participants (Pharmacokinetic sub study)
2. Pharmacokinetic assessments at steady state after four weeks of study drugs in a subset of study participants (Pharmacokinetic sub study)

Study Population and Study Duration

A total of 120 ART naive HIV-1 infected individuals with the indication to start antiretroviral treatment according to WHO and country guidelines will be enrolled at two study sites in Côte d'Ivoire and Tanzania. Each of the two sites will enroll 60 participants (15 participants per arm). For the PK Sub-Study 6 participants per study arm (total 24 participants will be included.

A minimum of 30% gender representation (female or male) participants will be requested per site. Recruitment, screening and enrollment of study participants are expected to be completed after 9 months. Patient treatment is 24 weeks. So patient related study procedures will take 15 months.