The document discusses several studies on HIV prevention efforts and viral replication. It summarizes trial results showing some vaccine and microbicide trials were disappointing or even dangerous for participants. It also discusses factors influencing viral replication rates in different cell types like metabolic activity and transcription activity. Key host proteins like APOBEC3G, NFAT, and Cyclin-T that are required for HIV infection are identified. A hypothetical virological synapse is discussed as a mechanism for direct cell-to-cell transmission without producing extracellular virus.

1. 2008: een moment van reflectie Resultaten van (dure) trial erg teleurstellend Vaccins The STEP trial Microbicide Soms zelfs gevaarlijk voor deelnemers HIV 2008 3. From: Cohen, Science 2008, 321, 902-3 Efficacy trials of biomedical prevention Intervention Completed Effective Male circumcision 3 3 HSV-2 suppression 2 0 Bacterial STI treatment 5 1 Cervical barriers 1 0 Microbicides 9 0 Vaccines 4 0 Total 24 4

2. HIV 2008 3. Stevenson Nat Med 9, 2003, 853-860

3. Virus half-life in different cells Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3.

4. Dependent on Metabolic activity of the cell Cellular activity in general Transcriptional activity in general at integration site Cellular half-life Virus half-life in different cells Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3.

5. Viral replication in host cells Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. Interleukine stimulation of G 0 -cells?

6. Cellular factors influencing viral replication Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. Several steps only in active cells

7. Cellular factors influencing viral replication Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. NFAT Several steps only in active cells

8. Cellular factors influencing viral replication Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. APOBEC3G NFAT Several steps only in active cells

9. Cellular factors influencing viral replication Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. APOBEC3G NFAT Cyclin-T Several steps only in active cells

10. Cellular factors influencing viral replication Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. APOBEC3G NFAT Cyclin-T HSP68 Several steps only in active cells

11. Identification of host proteins required for HIV infection Brass et al., Sciencexpress, Jan 10, 2008 HIV 2008 3. Inserted 170108

12. A hypothetical virological synapse Sattentau, Nature Rev Microbiol. 6 (2008) 815-826 No extracellular virus Escape from Ab HIV 2008 3.

13. Direct and indirect effects of HIV Stevenson, Nature Med 9, 2003, 853-860 HIV 2008 3. Carefully controlled apoptosis

14. Time course of HIV-induced cell death HIV 2008 3. ======= uit =======