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.

Treatment as prevention (TasP) and perceived sexual changes in behavior among HIV-positive persons: a French survey in infectious diseases departments in Paris.

We evaluated awareness of treatment as prevention (TasP) among adults people living with HIV (PLHIV) in five infectious disease departments in Paris, then how they perceived its impact on their sexual well-being. This cross-sectional multicenter survey was conducted in 2014 during scheduled clinical appointments using a self-administered questionnaire. We analyzed 520 questionnaires (42% women, 54% men of whom 57% were MSM [men who have sex with men]). 75% of women were born abroad, most commonly in sub-Saharan Africa, whereas 64% of men were French-born. The mean time since HIV diagnosis was 12.8 ± 7.8 years. Eighty-seven percent [84-90%]95% reported being aware of the impact of ART on HIV transmission, 94% MSM, 86% women, 83% heterosexual men. PLHIV reported that they gained awareness of TasP through medical doctors (86%). The fear of transmission was perceived as alleviated for 73% [69%;78%]95%, more often among MSM; the sexual life was reported to be improved for 28% [24%;33%]95%; and ART adherence to be improved for 45% [40%;50%]95%, more often among women. The awareness of TasP was relatively high, but it seems important to understand the features of male and female populations of PLHIV to adapt counseling during follow-up appointments, as women's answers differed in various regards.

Short Communication: Extremely Severe CD4 Lymphopenia During HIV-1 Primary Infection.

We report the case of a patient with a very profound CD4 T cell lymphopenia <20 cells/mm3 in the context of a primary HIV-1 infection, associated with both delayed HIV-specific antibody and CD8 T cell responses. A long-term immune reconstitution was observed after immediate initiation of antiretroviral therapy.

First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human Immunodeficiency Virus Type 2 (HIV-2) Infection: A Phase 2, Noncomparative Trial (ANRS 159 HIV-2).

Background: New options for first-line treatment of human immunodeficiency virus type 2 (HIV-2) infection are needed. We evaluated an integrase inhibitor (raltegravir)-containing regimen. Methods: Antiretroviral therapy (ART)-naive adults with symptomatic infection by HIV-2 only, CD4 count <500 cells/µL or CD4 decrease >50 cells/µL/year over the past 3 years, or a confirmed plasma HIV-2 RNA (pVL) load ≥100 copies/mL were eligible for this noncomparative trial. The composite primary endpoint was survival at 48 weeks without any of the following: CD4 gain from baseline <100 cells/µL, confirmed pVL ≥40 copies/mL from week 24, raltegravir permanent discontinuation, or incident B or C event. HIV-2 ultrasensitive pVL (uspVL) and total DNA were assessed using in-house polymerase chain reaction (PCR) assays. Results: Baseline median CD4 count of 30 enrolled individuals (67% women) was 436 cells/µL (interquartile range [IQR], 314-507 cells/µL); pVL was ≥40 copies/mL in 67% of them, uspVL was ≥5 copies/mL in 92%, and total DNA was >6 copies by PCR in 32%. At week 48, the composite endpoint of success was reached in 40% [95% confidence interval, 22.7%-59.4%]. Failure was mainly (50%) due to CD4 gain <100 cells/µL; uspVL was <5 copies/mL in 87% and total DNA >6 copies by PCR in 12% of participants. Median CD4 gain was 87 cells/µL (IQR, 38-213 cells/µL; n = 28). No serious adverse reactions were reported. Conclusions: Raltegravir-containing ART is a safe option for first-line treatment of HIV-2 infection, yielding a comparable success rate to protease inhibitors. Clinical Trials Registration: NCT 01605890.

Minority resistant variants are also present in HIV-2-infected antiretroviral-naive patients.

Objectives: To assess the prevalence of minority resistant variants (MRV) and X4-tropic minority variants in ART-naive HIV-2-infected patients. Patients and methods: ART-naive HIV-2-infected patients with detectable plasma viral load (>100 copies/mL) included in the ANRS HIV-2 CO5 Cohort were assessed. We performed ultra-deep sequencing (UDS) of protease, RT, integrase and gp105 regions. Only mutations in the HIV-2 ANRS list >1% were considered. HIV-2 tropism was assessed by V3 loop region UDS, and each read was interpreted with determinants of CXCR4-coreceptor use. Results: Among the 47 patients assessed, three displayed plasma viruses with a resistance-associated mutation (RAM) above the 20% detection threshold, all in RT, resulting in a prevalence of transmitted drug resistance for NRTI of 7.9% (95% CI 0.0%-16.5%). No RAM above the 20% detection threshold was found in protease or integrase. At the 1% detection threshold the transmitted drug resistance prevalence was 9.8% (95% CI 0.6%-19.0%), 13.2% (95% CI 3.5%-22.9%) and 4.5% (95% CI 0%-17.5%) for PI, NRTI and integrase inhibitors. The most prevalent MRV was the PI RAM I50V detected in three samples. Tropism analysis showed that 21% of patients (4 of 19) exhibited X4-tropic viruses: two in majority proportion and two in minority proportions (1.5% and 1.9%). Conclusions: In this first study assessing the prevalence of MRV in HIV-2 infection among ART-naive patients, we observed a 2-3-fold higher prevalence of RAM when a 1% detection threshold of mutations was used compared with a 20% threshold. Similarly, the proportion of patients with X4-tropic viruses was twice as high when UDS was used.