Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083

Abstract

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.

Keywords: HIV; HPTN 083; TDF-FTC; cabotegravir; injectable; long-acting; men who have sex with men; preexposure prophylaxis; prevention.

FIG 1

Summary of key events and laboratory results for participants in the cabotegravir (CAB) study arm of HPTN 083: cases D5 (A) and D6 (B). Results from testing performed at study sites are shown in File S2 in the supplemental material. Test results and key study events are shown as a function of the number of weeks from study enrollment based on calendar dates. Results obtained from testing performed at the HPTN Laboratory Center are shown above each graph. Positive and reactive results are indicated with a plus sign; negative and nonreactive results are indicated with a minus sign. IND indicates an indeterminate test result. VL values are shown (number of HIV RNA copies per milliliter); results noted as <40 indicate that HIV RNA was detected at a level below 40 copies/mL. Results from HIV drug resistance testing are shown. All drug resistance mutations are shown for INSTIs; major INSTI mutations are shown in boldface type. The brackets at the top of the graphs show the number of days between the last injection and the first HIV-positive visit. The lower brackets show the number of days between the first site-positive visit and the first HIV-positive visit for cases where there was a delay in site detection. The graphs show plasma CAB concentrations and key events. The key at the bottom describes the symbols used in the graphs. Horizontal lines indicate the following concentration cutoffs: 1.33 μg/mL for 8× PA-IC₉₀ (in vitro protein-adjusted 90% CAB inhibitory concentration), 0.664 μg/mL for 4× PA-IC₉₀, and 0.166 μg/mL for 1× PA-IC₉₀. BLQ indicates that the CAB concentration was below the limit of quantification (<0.025 μg/mL). Shaded areas indicate that the participant was on antiretroviral therapy. 3TC, lamivudine; Ag/Ab, antigen/antibody; DRVr, ritonavir-boosted darunavir; EFV, efavirenz; ND, not detected; TDF, tenofovir disoproxil fumarate.

FIG 2

Summary of key events and laboratory results for participants in the cabotegravir (CAB) study arm of HPTN 083: cases DX1 (A), DX2 (B), and DX3 (C). Results from testing performed at study sites are shown in File S2 in the supplemental material. Test results and key study events are shown as a function of the number of weeks from study enrollment based on calendar dates. Results obtained from testing performed at the HPTN Laboratory Center are shown above each graph. Positive and reactive results are indicated with a plus sign; negative and nonreactive results are indicated with a minus sign. IND indicates an indeterminate test result. VL values are shown (number of HIV RNA copies per milliliter); results noted as <40 indicate that HIV RNA was detected at a level below 40 copies/mL. Results from HIV drug resistance testing are shown. All drug resistance mutations are shown for INSTIs. Major drug resistance mutations for other drug classes are shown in blue text in parentheses. The brackets at the top of the graphs show the number of days between the last injection and the first HIV-positive visit. The graphs show plasma CAB concentrations and key events. The key at the bottom describes the symbols used in the graphs. Horizontal lines indicate the following concentration cutoffs: 1.33 μg/mL for 8× PA-IC₉₀ (in vitro protein-adjusted 90% CAB inhibitory concentration), 0.664 μg/mL for 4× PA-IC₉₀, and 0.166 μg/mL for 1× PA-IC₉₀. BLQ indicates that the CAB concentration was below the limit of quantification (<0.025 μg/mL). Shaded areas indicate that the participant was on antiretroviral therapy. Ag/Ab, antigen/antibody; EFV, efavirenz; FTC, emtricitabine; ND, not detected; TDF, tenofovir disoproxil fumarate; WT, wild type (no RAMs detected); XTC, lamivudine or emtricitabine.

FIG 3

Summary of key events and laboratory results for participants in the cabotegravir (CAB) study arm of HPTN 083: cases BR1 (A) and BR2 (B). Results from testing performed at study sites are shown in File S2 in the supplemental material. Test results and key study events are shown as a function of the number of weeks from study enrollment based on calendar dates. Results obtained from testing performed at the HPTN Laboratory Center are shown above each graph. Positive and reactive results are indicated with a plus sign; negative and nonreactive results are indicated with a minus sign. IND indicates an indeterminate test result. VL values are shown (number of HIV RNA copies per milliliter). Results from HIV drug resistance testing are shown. All drug resistance mutations are shown for INSTIs; major INSTI mutations are shown in boldface type. Major drug resistance mutations for other drug classes are shown in blue text in parentheses. The brackets at the top of the graph show the number of days between the last injection and the first HIV-positive visit. Lower brackets show the number of days between the first site-positive visit and the first HIV-positive visit for cases where there was a delay in site-detection. The graphs show plasma CAB concentrations and key events. The key at the bottom describes the symbols used in the graphs. Horizontal lines indicate the following concentration cutoffs: 1.33 μg/mL for 8× PA-IC₉₀ (in vitro protein-adjusted 90% CAB inhibitory concentration), 0.664 μg/mL for 4× PA-IC₉₀, and 0.166 μg/mL for 1× PA-IC₉₀. BLQ indicates that the CAB concentration was below the limit of quantification (<0.025 μg/mL). Shaded areas indicate that the participant was on antiretroviral therapy. The blue arrow indicates that tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) was dispensed for preexposure prophylaxis. TFV indicates the concentration of tenofovir in plasma (nanograms per milliliter). 3TC, lamivudine; Ag/Ab, antigen/antibody; DTG, dolutegravir; EFV, efavirenz; ND, not detected; WT, wild type (no RAMs detected).