Dan Turner

In Israel, irregular migrants (IMs) living with human immunodeficiency virus (HIV-1) that have no access to regular health insurance are provided with HIV-1-related health coverage under a public–private partnership (PPP) program initiated by the Ministry of Health in 2014. Here we characterized IMs referred to the PPP in 2019–2024 and used a linear mixed-effects model to follow up their CD4 and HIV-1 viral load (VL) counts for a median period of 16 months. Subtypes, resistance mutations and phylogenetic relationships were determined in all cases with viral failure and in selected cases with available blood remains. A total of 231 of 238 referred to the PPP initiated antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors (NRTIs) and either non-nucleoside reverse transcriptase inhibitors (NNRTIs, 61.5%, 142/231) or protease inhibitors (PIs, 38.5%, 89/231). Irrespective of the treatment regimen, all these individuals increased their CD4 and decreased their VL trajectories over time (p < 0.001). However, mixed model analysis revealed two classes of CD4 trajectory patterns. Comparison between these two patterns revealed that Class-1 individuals started with lower initial CD4 counts compared to Class-2 individuals (median of 115 cells/mm³, IQR 70–171 compared to median of 312 cells/mm³, IQR 104–510, p < 0.001) and experienced slower recovery compared to Class-2. Most Class-1 individuals originated from Africa (78% vs. 52%, p = 0.016). Treatment failure was observed in 5.6% of all individuals receiving treatment under the program. Sequencing analysis, enabled in 23% of the treated cohort, revealed that the reverse transcriptases (RT) M184V (13%) and K103N (7.4%) were the most prevalent mutations. Conclusively, while treatment was not consistent with current recommendations for first-line therapy, the virological and immunological response of most patients was favorable and the prevalence of cases with resistance mutations was not higher than that identified in people living with HIV-1 who are covered by the national health insurance. Despite the limitations of the PPP, this program may provide a unique therapeutic opportunity for IMs with HIV-1.

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010–2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010–2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015–2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01–3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF.

Recent studies have shown good serological and cellular immune responses in people living with human immunodeficiency virus (PLWH) after receipt of 2 doses of messenger RNAA (mRNA) severe acute respiratory syndrome coronavirus 2 vaccine. Data are missing regarding the response after 3 vaccine doses. We followed up a group of PLWH who received 3 doses of the mRNA BNT162b2 vaccine and for whom data of humoral immune response after 2 vaccine doses were available. Patients provided a blood sample 4–6 months after the booster dose. The aim of the study was to measure the serological and cellular response after the third dose and to evaluate factors associated with the vaccine response. Fifty patients have provided a serum sample for serological evaluation after the booster. The anti–receptor-binding domain (RBD) immunoglobulin (Ig) G titers were higher after the booster with a median delta of 3240 arbitrary units/mL. The median CD4⁺ T-cell count was 660/μL (interquartile range, 515–958/μL) and had no influence on the antibody level. Factors associated with lower delta included higher CD8⁺ T-cell count (P = .02) and longer time between the third dose and the blood test (P = .01). Higher anti-RBD IgG titer after the second vaccine (P = .03), as well as a longer interval between second and third doses (P = .031) were associated with higher delta. There was no increase in the median number of activated interferon γ⁺ and tumor necrosis factor α⁺ CD4⁺ T cells after the booster (n = 8). The anti-RBD IgG level after 3 doses of mRNA BNT162b2 vaccine was higher than the level after 2 doses, suggesting additional value of the booster. Cellular response did not further increase after a booster.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.

Monitoring HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs) is important for disease surveillance. Recombination may affect prevention efforts and interfere with the diagnosis and treatment of HIV-1 infection. Here, we characterized the epidemiology of HIV-1 CRFs and URFs in Israel. Partial pol sequences from treatment naïve patients diagnosed in 2010–2018 were assessed using the recombinant identification program (RIP), the recombinant detection program (RDP5), and using the maximum-likelihood phylogenetic method, using 410 reference sequences obtained from the Los Alamos database. CRFs and URFs were identified in 11% (213/1940) of all sequenced cases. The median age at diagnosis was 38 (30–47) years, 61% originated from Israel, and 82% were male. The most common were CRF02_AG (30.5%), CRF01_AE (16.9%), and the more complex forms CRF01_AE/CRF02_AG/A3 (10.8%) and B/F1 (7%). A significant increase in their overall proportion was observed in recent years (8.1% in 2010–2012, 20.3% in 2016–2018, p < 0.001). This increase was most prominent in individuals carrying CRF02_AG (2.5% in 2010–2015, 9.8% in 2016–2018, p < 0.001). Men who have sex with men (MSM) was the most common risk group; however, those infected with the secondary recombinant CRF02_AG/A6 were mainly injecting drug users (IDUs). The most common resistance mutations were K103N (5/213, 2.3%) and E138A (18/213, 8.5%) in the reverse transcriptase. Only E138A was more frequent in the recombinants compared with the classic subtypes and was significantly associated with a specific secondary CRF, CRF02_AG/A4. We concluded that CRFs and URFs were mainly detected in Israeli-born MSM and that an increase in the overall proportion of such HIV-1 sequences could be observed in more recent years.

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

HIV-infected (HIVI) men who have sex with men (MSM) may transmit HIV to their sero-discordant sex partner/s. This study assesses the knowledge, attitudes and sex-practices of Israeli HIVI-MSM. This cross-sectional study compared HIVI-MSM to self-reported HIV-uninfected (HIVU) MSM by using anonymous questionnaires that were distributed in AIDS-treatment centers and gay-related internet-sites in 2015. Unprotected anal intercourse (UAI) in the last 6 months was the outcome variable. Of 300 HIVI-MSM and 1299 HIVU-MSM, UAI with sero-discordant/unknown-status partner/s was performed by 12.1% and 17.9%, respectively, p=0.02. UAI with sero-discordant/unknown-status among HIVI-MSM and HIVU-MSM was associated with the type of partnership: 37.7% vs. 52.4% for steady partner/s, 19.0% vs. 39.9% for sex-buddies and 23.5% vs. 24.0% for casual partner/s (p<0.001, p=0.01, p=0.6), respectively. On these occasions, HIVI-MSM were more likely to be receptive during UAI: 92.3%, 87.5% and 83.3% for steady partner/s, sex buddies and casual partner/s, respectively. In cases HIVI-MSM performed UAI, 31.3% expected their partner/s to share responsibility for condom-use vs. 9.7% of HIVU-MSM. HIVI-MSM were involved in risky sexual-behaviors, such as substances-use, earlier sexual debut and sex for money. HIVI-MSM were more likely to disclose their HIV-status with their partner before sex and demonstrated better knowledge about HIV-transmission than HIVU-MSM. HIVI-MSM performed UAI with sero-discordant/unknown-status partner/s less frequently than HIVU-MSM. Their condom-use practices were associated with the type of partner, and were lower for casual vs. steady partners or sex-buddies. HIVI-MSM tended to use sero-adaptive strategies to reduce the potential risk of HIV-transmission to their sero-discordant/unknown-status partner/s.