Prevalence and incidence of HEV among men using HIV pre-exposure prophylaxis: A sub-study of the ANRS IPERGAY trial.

BACKGROUND: Men who have sex with men (MSM) have an increased risk of infection by pathogens transmitted by the oro-fecal route. Here, we investigated the seroprevalence and incidence of hepatitis E virus (HEV) infection in 416 MSM included in the ANRS IPERGAY PrEP trial. RESULTS: Among the 62 (14.9% (95% CI: [11.6%-18.7%]) seropositive for HEV at inclusion, the only factor associated with testing seropositive for HEV was older age. Geographical origin, use of recreational drugs, number of sexual partners, status for HAV and bacterial sexually transmitted infection (STI) at inclusion were not associated. Among the 342 HEV-seronegative patients with available samples, 9 seroconverted after a median of follow-up of 2.1 years (IQR (interquartile range): [1.6; 3.0]). CONCLUSION: Overall, the HEV incidence was 1.19% per 100 person-years [95% CI: 0.54%; 2.26%]. Sexual transmission does not seem to be a major route of HEV infection in MSM, unlike HAV.

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

In-depth Sampling of High-risk Populations to Characterize HIV Transmission Epidemics Among Young MSM Using PrEP in France and Quebec.

BACKGROUND: A better understanding of HIV transmission dynamics among populations at high risk is important for development of prevention strategies. We determined HIV transmission networks from infected individuals enrolled in the pre-exposure prophylaxis (PrEP) IPERGAY trial in combination with the ANRS PRIMO and Montreal PHI cohorts to identify and characterize active clusters of transmission in this high-risk population. METHODS: Genotypic resistance tests were performed on plasma samples from 31 IPERGAY participants. Reverse transcriptase sequences were analyzed in combination with unique HIV pol sequences from 1351 individuals enrolled in the PRIMO ANRS cohort (1999-2014) and 511 individuals enrolled in the Montreal PHI cohort (1996-2016). Network analyses were performed to infer putative relationships between all participants. RESULTS: Overall, 1893 participants were included. Transmission network analyses revealed that 14 individuals (45.2%) from the IPERGAY trial were involved in 13 clusters sampled over a median period (interquartile range) of 2 (0.3-7.8) years, including 7 dyads and 6 larger clusters ranging from 4 to 28 individuals. When comparing characteristics between clustering individuals enrolled in the PRIMO cohort (n = 377) and in IPERGAY (n = 14), we found that IPERGAY participants had a higher viral load (5.93 vs 5.20 log10 copies/mL, P = .032) and reported a higher number of partners in the last 2 months (P < .01). CONCLUSIONS: These results demonstrate high rates of HIV transmission clustering among young high-risk MSM enrolled in the IPERGAY trial. In-depth sampling of high-risk populations may help to uncover unobserved transmission intermediaries and improve prevention efforts that could be targeted to the most active clusters.

Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial.

OBJECTIVES: To compare the incidence of clinical lipodystrophy in HIV-1-infected patients receiving zidovudine or stavudine, in combination with indinavir and lamivudine, in a randomized trial. METHODS: NOVAVIR was a randomized multicentre trial comparing stavudine/lamivudine/indinavir and zidovudine/lamivudine/indinavir in 170 patients pretreated with zidovudine, didanosine or zalcitabine (> 6 months), but naive for lamivudine, stavudine and protease inhibitors. The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of 101 patients after 30 months of follow-up. RESULTS: The incidence of lipoatrophy was increased in the stavudine arm versus the zidovudine arm, as followed: facial atrophy: 48 versus 22% of patients, P = 0.011, lower limb atrophy: 49 versus 22% of patients, P = 0.006, buttock atrophy: 47 versus 20% of patients, P = 0.009, venomegaly: 57 versus 24% of patients, P = 0.001. There was no significant difference in the incidence of clinical signs of central fat accumulation nor in fasting metabolic parameters at month 30 between the two arms. In multivariate analyses, the stavudine arm, previous therapy with didanosine, and a lower CD4 cell count at study entry were associated with an increased risk of lipoatrophy, whereas older patients and women had an increased risk of lipohypertrophy. CONCLUSION: Patients receiving stavudine/lamivudine/indinavir had a greater rate of clinical lipodystrophy, mainly lipoatrophy, than those treated with zidovudine/lamivudine/indinavir.

Characteristics of non-Hodgkin lymphoma arising in HIV-infected patients with suppressed HIV replication.

OBJECTIVE: Despite effective treatment of HIV infection, some patients still develop non-Hodgkin lymphoma (NHL). We analysed patients with HIV-associated NHL and undetectable plasma HIV-RNA, according to the duration of HIV suppression. METHODS: Out of 388 patients included in a prospective cohort of HIV-associated NHL from 1996 to 2008, 128 (33%) had a plasma HIV-RNA below 500 copies/ml and were included in the study. Patients with long-term HIV suppression (>18 months) were compared with patients with recent HIV suppression (< or = 18 months). RESULTS: All patients but three were treated with combination antiretroviral therapy, with a median duration of 2.2 years. The median duration of HIV suppression was 10.1 months. Most cases (65%) occurred within 18 months following HIV suppression. In the more than 18 months group, patients developed NHL at a higher CD4 cell count than patients with 18 months or less of HIV suppression (359 versus 270 cells/microl, P = 0.02). None of the NHL characteristics were different between the two groups. Outcome was similar in the two groups (complete remission, 64 versus 72.5%; P = 0.35 and 3-year survival, 46 versus 56%; P = 0.08). In addition, 52% of the tumours were Epstein-Barr virus or human herpesvirus 8 associated, without any difference in the proportion of virus-associated tumours according to the duration of HIV suppression. CONCLUSION: In patients with undetectable HIV-RNA, NHL occurred mainly within the first 18 months following HIV suppression. In patients developing NHL after long-term HIV suppression, the level of CD4 cell count was higher, but the association with Epstein-Barr virus or human herpesvirus 8 and the prognosis were similar to that observed in patients with recent HIV suppression.