PrEPVacc / PV1

278 participants will receive DNA-HIV-PT123 vaccine and AIDSVAX® B/E protein at weeks 0, 4, 24 and 48. 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml of AIDSVAX® B/E will be injected into the deltoid muscle of the right arm 1 tab of Truvada (0-26 weeks) Biological: Vaccine Group A: DNA-HIV-PT123 and AIDSVAX® B/E (weeks 0,4,24,48) DNA-HIV-PT123 HIV vaccine includes three DNA plasmids that encode clade C ZM96 Gag, clade C ZM96 Env, and CN54 Pol-Nef. AIDSVAX® B/E is a bivalent HIV gp120 glycoprotein encompassing both subtype B (MN) and subtype E (A244) proteins that are adsorbed onto 600mcg of aluminum hydroxide gel suspension as adjuvant. Drug: Control PrEP:TDF/FTC once daily (weeks 0-26) Each tablet of Truvada contains 245mg of tenofovir disoproxil (TDF) and 200mg of emtricitabine (FTC), both of which are nucleot/side analogue HIV-1 reverse transcriptase inhibitors. Other Name: Truvada

278 participants will receive Sodium Chloride 0.9% (Normal Saline) placebo at weeks 0,4,24, and 48 The volume will be matched to the vaccine at 1ml for DNA, MVA and AIDSVAX® B/E, but 0.4ml for CN54gp140 in MPLA-L. Participants will be randomly divided in a 1:1 ratio to receive 1ml in each arm at the four timepoints or 1ml in the left arm and 0.4ml in the right arm at the four timepoints. 1 tab of Truvada (0-26 weeks) Biological: Vaccine Group C: Saline placebo (weeks 0,4,24,48) Sodium Chloride (NaCl) for injection, 0.9% Drug: Control PrEP:TDF/FTC once daily (weeks 0-26) Each tablet of Truvada contains 245mg of tenofovir disoproxil (TDF) and 200mg of emtricitabine (FTC), both of which are nucleot/side analogue HIV-1 reverse transcriptase inhibitors. Other Name: Truvada

278 participants will receive DNA-HIV-PT123 and CN54gp140+MPLA-L at weeks 0 and 4, then MVA and CN54gp140+MPLA-L at weeks 24 and 48 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml (1x108 pfu) of MVA will be injected into the deltoid muscle of the left upper arm 0.4mL containing a mixture of 100mcg CN54gp140 and 5mcg MPLA-L will be injected into the deltoid muscle of the right upper arm 1 tab of Descovy (0-26 weeks) Biological: Vaccine Group B: DNA-HIV-PT123 and CN54gp140+MPLA-L (weeks 0,4), then MVA and CN54gp140+MPLA-L (weeks 24,48) DNA-HIV-PT123 (see above) CN54gp140+MPLA-L. Recombinant CN54gp140 is a HIV-1 envelope protein from the clade C strain 97/CN/54 isolate, which comprises a sequence of 634 amino acids. MPLA is a non-toxic version of LipoPolySaccharide (LPS), which is isolated from the LPS lipid A region of Salmonella Minnesota R595 and retains the immune-stimulatory properties of LPS, but exhibits low toxicity. MVA-CMDR (Modified Vaccinia Ankara-Chiang Mai Double Recombinant) is a non-replicating, highly attenuated strain of Vaccina virus that has been genetically engineered to express the HIV-1 genes envgp160 CM235 Subtype E and gag and pol CM240 Subtype A (integrase-deleted and reverse transcriptase non-functional). Drug: Experimental PrEP:TAF/FTC once daily (weeks 0-26) Each tablet of Descovy contains 25mg of tenofovir alfenamide (TAF) and 200mg of emtricitabine (FTC), both of which are nucleot/side analogue HIV-1 reverse transcriptase inhibitors. Other Name: Descovy