CXCR3 and CXCR5 are highly expressed in HIV-1-specific CD8 central memory T cells from infected patients.

New ways of characterizing CD8+ memory T cell responses in chronic infections are based on the measurement of chemokine receptor expression (CXCR3, CXCR5, and CX3CR1). We applied these novel phenotyping strategies to chronic HIV infection by comparing healthy donors (HDs), HIV-infected patients receiving antiretroviral therapy (ART), and spontaneous HIV controllers (HICs). In all groups, the memory cells exhibited high proportion of CXCR3+ cells. Proportions of CXCR5+ and CX3CR1+ cells were preferentially observed among central memory cells (Tcm) and effector memory cells (Tem) respectively. Chronic controlled HIV infection impacted the chemokine receptor profile of both HIV-specific and nonspecific CD8+ T cells. In total CD8+ T cells, the proportions of CXCR3- CXCR5- CX3CR1- Tcm and Tem were lower in HIV-infected patients than in HDs with subtle differences between ART and HICs. Such phenotyping strategy also revealed differences in exhaustion and senescence phenotypes, the CXCR3+ CXCR5+ CX3CR1- being more exhausted and senescent than the CXCR3+ CXCR5- CX3CR1- Tcm fraction. Among HIV-specific CD8+ T cells, the vast majority of Tcm cells were CXCR3+ and CXCR5+ cells in contrast with their nonspecific counterparts. In conclusion, the addition of migration markers contributes to better characterize Tcm/Tem compartment.

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection.

BACKGROUND: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. METHODS: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers. FINDINGS: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. INTERPRETATION: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. FUNDING: ANRS and Paris-Saclay University.

Common evolutionary features of the envelope glycoprotein of HIV-1 in patients belonging to a transmission chain.

The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. While it was generally assumed that the neutralizing antibody (NAb) response depended mainly on the infected individual, the concept that virus-related factors could be important in inducing this response has recently emerged. Here, we analyzed the influence of the infecting viral strain in shaping NAb responses in four HIV-1 infected subjects belonging to a transmission chain. We also explored the impact of NAb responses on the functional evolution of the viral quasispecies. The four patients developed a strong autologous neutralizing antibody response that drove viral escape and coincided with a parallel evolution of their infecting quasispecies towards increasing infectious properties, increasing susceptibility to T20 and increasing resistance to both CD4 analogs and V3 loop-directed NAbs. This evolution was associated with identical Env sequence changes at several positions in the V3 loop, the fusion peptide and the HR2 domain of gp41. The common evolutionary pattern of Env in different hosts suggests that the capacity of a given Env to adapt to changing environments may be restricted by functional constraints that limit its evolutionary landscape.

Calendar trends in sexual behaviours in a cohort of HIV-infected MSM at the era of treatment as prevention of HIV infection.

BACKGROUND: With the advent of treatment as prevention of HIV infection (TasP), we assessed trends in sexual behaviours between 2000 and 2017 among HIV-infected MSM enrolled in the French ANRS PRIMO cohort. METHODS: At each cohort visit, a clinical questionnaire including laboratory values was completed and a self-administered questionnaire was used to collect sexual behaviours, that is, the number, type (steady/casual) and HIV status (positive or negative/unknown) of partners, and condom use. The possible influence of viral load (undetectable/detectable) measured at the preceding visit on the evolution over time of sexual behaviour was assessed with logistic regression models fitted by generalized estimating equations (GEE), taking into account longitudinal data. RESULTS: We analyzed data from 10657 follow-up visits by 1364 MSM. Overall, whatever the considered behavioural variable: at least one sexual partner, steady and/or casual, condomless sex with steady, casual partners, serodiscordant or not, we observed a calendar increase with a particularly more marked rise from 2010 (P < 0.0001). Inconsistent condom use did not differ according to the viral load status (detectable vs. undetectable). Trends in inconsistent condom use increased across different generations of MSM, as defined by the year they were diagnosed with HIV infection. CONCLUSIONS: 'Having a sexual partner' and condomless sex, both increased in frequency between 2000 and 2017. Viral load status did not influence condom use as could have been expected from the 2008 Swiss Statement.

Does transient cART started during primary HIV infection undermine the long-term immunologic and virologic response on cART resumption?

BACKGROUND: We explored the impact of transient cART started during the primary HIV-infection (PHI) on the long-term immunologic and virologic response on cART resumption, by comparison with treatment initiation during the chronic phase of HIV infection (CHI). METHODS: We analyzed data on 1450 patients enrolled during PHI in the ANRS PRIMO cohort between 1996 and 2013. "Treatment resumption" was defined as at least 3 months of resumed treatment following interruption of at least 1 month of treatment initiated during PHI. "Treatment initiation during CHI" was defined as cART initiated ≥6 months after PHI. The virologic response to resumed treatment and to treatment initiated during CHI was analyzed with survival models. The CD4 cell count dynamics was modeled with piecewise linear mixed models. RESULTS: 136 patients who resumed cART for a median (IQR) of 32 (18-51) months were compared with 377 patients who started cART during CHI for a median of 45 (22-57) months. Most patients (97%) achieved HIV-RNA <50 cp/mL after similar times in the two groups. The CD4 cell count rose similarly in the two groups during the first 12 months. However, after 12 months, patients who started cART during CHI had a better immunological response than those who resumed cART (p = 0.01); therefore, at 36 months, the gains in √CD4 cells/mm(3) and CD4% were significantly greater in patients who started treatment during CHI. CONCLUSION: These results suggest that interruption of cART started during PHI has a significant, albeit modest negative impact on CD4 cell recovery on cART resumption.