Prevalence of HIV Infection and Resistance Mutations in Patients Hospitalized for Febrile Illness in Indonesia

ABSTRACT. HIV prevalence in Indonesia is increasing, and only 64% of infected individuals know their status. In a prospective cohort of 1,453 hospitalized patients with unexplained fever, 46 (3.2%) had HIV, including 15 (1.1%) patients without a prior HIV diagnosis. Among 31 subjects previously known to have HIV, 21 (68%) had been receiving combination antiretroviral therapy (cART) at the time of enrollment. Of 39 HIV cases with HIV RNA levels ≥ 100 copies/mL, sequencing for genotype analysis and resistance testing was successful in 30 (77%) subjects. The most common HIV subtypes were AE (90%) and B (10%). Five (16.7%) subjects had resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors, and all of them were on cART. No evidence of transmitted drug resistance was found in newly diagnosed individuals. Hospital-based screening may be an efficient method to expand HIV testing and identify a significant number of new cases. Access to care, close monitoring, expansion of anti-retroviral options, and ensuring availability of CD4 determinations, viral load testing, and genotyping are crucial to control of the epidemic in Indonesia.

HIV-1 subtype diversity and transmission strain source among men who have sex with men in Guangxi, China

With the rapid increase in HIV prevalence of men who have sex with men (MSM) in recent years and common human migration and travelling across different provinces in China, MSM are now finding it easier to meet each other, which might contribute to local HIV epidemics as well as fueling cross-province transmission. We performed a cross-sectional survey in 2018–2019 to investigate the current HIV subtype diversity and inferred HIV strain transmission origin among MSM in Guangxi province, China based on a phylogenetic analysis. Based on 238 samples, we found that the HIV-1 subtype diversity was more complicated than before, except for three major HIV subtypes/circulating recombinant forms (CRFs): CRF07_BC, CRF01_AE, CRF55_01B, five other subtypes/CRFs (CRF59_01B, B, CRF08_BC, CRF67_01B, CRF68_01B) and five unique recombinant forms (URFs) were detected. In total, 76.8% (169/220) of samples were infected with HIV from local circulating strains, while others originated from other provinces, predominantly Guangdong and Shanghai. The high diversity of HIV recombinants and complicated HIV transmission sources in Guangxi MSM indicates that there has been an active sexual network between HIV positive MSM both within and outside Guangxi without any effective prevention. Inter-province collaboration must be enforced to provide tailored HIV prevention and control services to MSM in China.

Pharmacological activation of the circadian component REV-ERB inhibits HIV-1 replication

Human immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks a curative therapy or vaccine. Despite the reduction in AIDS-related deaths achieved by current antiretroviral therapies, drawbacks including drug resistance and the failure to eradicate infection highlight the need to identify new pathways to target the infection. Circadian rhythms are endogenous 24-hour oscillations which regulate physiological processes including immune responses to infection, and there is an emerging role for the circadian components participating viral replication. The molecular clock consists of transcriptional/translational feedback loops that generate rhythms. In mammals, CLOCK and BMAL1 activate rhythmic transcription of genes including the nuclear receptor REV-ERBα, which represses BMAL1 and plays an essential role in sustaining a functional clock. We investigated whether REV-ERB activity regulates HIV-1 replication, and found REV-ERB agonists inhibited HIV-1 promoter activity in cell lines, primary human CD4 T cells and macrophages, whilst antagonism or genetic disruption of REV-ERB increased promoter activity. Furthermore, the REV-ERB agonist SR9009 inhibited promoter activity of different HIV-subtypes and HIV-1 replication in primary T cells. This study shows a role for REV-ERB synthetic ligands to inhibit HIV-1 LTR promoter activity and viral replication, supporting a role for circadian clock transcription factors in regulating HIV-1 replication.

PROFILE OF HCV GENOTYPES AND HIV-SUBTYPES AMONG HIV-COINFECTED PATIENTS IN SOUTHERN BRAZIL

ABSTRACT BACKGROUND: Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. METHODS: A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. RESULTS: During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. CONCLUSION: In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.

2506. Trends of Transmitted Resistance Mutations to Four Drug Classes, HIV-Subtypes And Herpesviruses Replication Among Subjects Recently Diagnosed as HIV Infected Over 2004–2019

Background to evaluate circulation of drug resistance mutations (DRMs), sub-types (ST) and Herpesviruses replication among subjects recently diagnosed as HIV infected (pts) in Veneto (Italy), over 16 years, comparing previously reported trends with the most recent one, updated to 2019. Methods on plasma from 2919 patients diagnosed from July 2004 to April 2019, protease (PR), reverse transcriptase (RT) and recently Integrase (In) were analyzed for DRMs, susceptibility profile (Stanford db) and ST. Potential low-level resistances were excluded. CMV-DNA and EBV-DNA were evaluated by in-house Real-Time-PCR in PBMCs. Results in 5 periods (2004/06, 07/09, 10/12, 13/16, 17–19) 334, 796, 752, 750 and 287 patients were recruited; non-B-ST were 21.9, 29.3, 33, 32.7 and 48.1% (33.5% Italians in 17–19), respectively. A significant increase of non-B-ST (P < 0.0001 for trend) and of the percentage of Italians with non-B-strains (P = 0.029) were observed. Resistance to PR or to multiple classes declined but not to non-nucleoside RT inhibitors (NNRTI) (Fig 1). E138A alone, not included in the previous evaluations, increased from 2.3 to 1.8, to 3.2, to 3.6, to 4.7% in 2017-19. No primary TDRM to In-Inhibitors (InIn) were found in 469 B-ST-Pts enrolled in 2014–19; 16% had major TDRM for RT/PI. Among 231 non-B patients, 12,5% with other TDRMs, only a 143C and a 66I were found. Accessory InIn-TDRMs were detected (Figures 2 and 3). Nevertheless, from 2009 to 2019 in Veneto 114 InIn-failed and potentially transmitters patients with In-DRMs were found. In 2017–19 17,3% of patients had CMV-DNA in PBMCs, with a median CD4 of 55 (8%), HIV-RNA 247251 cps/mL and EBV-DNA of 811 cps/106 PBMCs (3% were neg); Patients CMV-DNA-negative (82,7%) had median CD4 of 334 (18,9%), HIV-RNA 47770 cps/mL and a significantly lower EBV-DNA of 194 cps/106 PBMCs (15% were neg): differences between immuvirological variables were significant. Conclusion An increase of non-B strains and a slight increase of TDRMs among B-ST were observed. The persistent circulation of NNRTI-DRMs, the shortage of major In-TDRMs but a circulation of many In-polymorphisms have implications on the screening at baseline and on the selection of the first-line HAART. Many patients with lower CD4 and higher HIV replication has an incomplete control of co-infecting herpesviruses, which contribute to immunoactivation. Disclosures All authors: No reported disclosures.

PO 8597 NEUTRALISING AND NON-NEUTRALISING ANTIBODIES RESPONSE IN HIV-1-INFECTED INDIVIDUALS FROM MOZAMBIQUE

BackgroundA vaccine that protects against the different HIV subtypes circulating around the world is essential to control and eliminate HIV infection. The immunogens are the key to develop an effective HIV vaccine. In this study, we characterised the antibody response against recombinant C2V3C3 polypeptides from several HIV-1 subtypes and evaluated the neutralising antibody response.MethodsPlasmas from HIV-1-infected individuals under treatment (n=39) and drugs-naïve individuals (n=8) were tested in an ELISA assay to determine the presence of antibodies against polypeptides from HIV-1 subtypes (CRF02_AG, B, C, G and H). The neutralising activity of plasma was evaluated with a panel of six HIV-1 viruses from a reference panel, [one tier 1 (NL4.3), and five tier 2 (PCH119_CRF07, PCE1176_C, TRO11_B, 246 F3_AC and CRF07_BJOX2000)] in a TZM-bl cells-based assay.ResultsOut of 48 plasmas, 44 (89.6%) reacted at least with one polypeptide and four (10.4%) did not react with any polypeptide. Interestingly, 56% of the plasmas recognise ≥3 peptides and 6 reacted with all polypeptides. The polypeptide from virus CRF02_AG was the most antigenic (77%) followed by the polypeptide C (58.3%), G (58.3%), H (50%) and B (35.4%). There was a positive correlation between polypeptides number recognised and binding antibody reactivity (r=0.4895, p=0.0111). All plasmas from drugs-naïve individuals neutralised at least one virus with neutralising activity between 39.3% and 95.7%. Four plasmas showed neutralising activity >50% against five viruses. The virus 249 F3 was the easiest to neutralise (median, 65.7%), whereas PCH119_CRF07 was the most difficult to neutralise (median, 43.6%). Neutralising activity of plasmas from patients under treatment are ongoing.ConclusionIn summary, these polypeptides could be useful in vaccine design once they are very antigenic and we observed a heterologous neutralising antibody response in naïve patients that expressed positive antibody-response anti-peptides.

Travel-associated STI amongst HIV and non-HIV infected travellers

Background The incidence of sexually transmitted infections (STI) is increasing in Western countries whilst travel plays a major role in STI dissemination worldwide. However, there is no study distinguishing HIV-positive and HIV-negative travellers. Methods We retrospectively evaluated the epidemiological, clinical and biological characteristics of the patients diagnosed with a travel-related STI between 2008 and 2016. We describe and compare the spectrum of STI diagnosed amongst HIV-positive and negative travellers. Methods Overall, 163 travel-related STI were identified in 140 patients (89% male, 54% men having sex with men, 40% HIV-positive). Symptoms occurred during travel in 39% of them, otherwise the median time between return and symptoms’ onset was 13 days. Amongst the 84 HIV-negative travellers, the main STI were primary HIV infections (n = 36, 38%), Neisseria gonorrhoeae (NG) infections (17%) and primary herpes infection (14, vs 1.5% amongst HIV-positive travellers, P = 0.01). The regions of exposure to HIV were concordant with the known geographical distribution of HIV subtypes. Amongst the 56 HIV-positive travellers, the main STI were syphilis (43, vs 6% amongst HIV-negative travellers, P = 0.01), Chlamydia trachomatis (CT) infections (22, vs 13% amongst HIV-negative travellers, P = 0.08), NG infections (13%) and acute hepatitis C (12, vs 1% amongst HIV-negative travellers, P = 0.01), with a predominance of anal forms for both CT and NG infections. Conclusions The spectrum of STI diagnosed in returning travellers is broad with important differences according to HIV status. In our setting, primary HIV infection was the leading STI in non-HIV infected patients, which suggests that pre-exposure prophylaxis may have a role in HIV prevention in at-risk travellers.