Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010-2018

Abstract

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.

Keywords: HIV-1 spread; epidemiology; people living with HIV-1(PLHIV); transmitted drug-resistance mutations (TDRM).

Figure 1

Probability of TDRM by sex, age, birthplace, HIV-1 subtype and transmission group. Following logistic regression analysis assessing predictors of TDRM (Table S5), all predicted values of mean of response related to TDRM were preserved. Subsequently, the probability of TDRM (0.0–1.0) was derived. Here, multi-dimensional mapping visualizes the results of this analysis. TDRM-transmitted drug-resistance mutations; SSA—Sub-Saharan Africa; EEU/CA—Eastern Europe and Central Asia; WCEU/NA—Western and Central Europe and North America; IL—Israel; PWID—people who use injection drug; MSM—men who have sex with men; HETERO—heterosexual contacts.

Figure 2

Phylogenetic analysis of subtype C sequences, N = 313. A phylogenetic tree of the pol region of subtype C sequences from 313 HIV-1 patients using the maximum likelihood (ML) with GTR + G + I model is shown. Included are three reference sequences (Table S1). The tree was visualized in Fig Tree version 1.4.4. Clusters (bootstrap values > 0.7) are colored in grey. The regions of origin are colored as follows: SSA (Sub-Saharan Africa) in navy blue; EEU/CA (Eastern Europe and Central Asia) in red; WCEU/NA (Western and Central Europe and North America) in orange; IL (Israel) in light green; other/unknown birthplace in turquoise; reference sequences in purple. PWID—people who use injection drug; MSM—men who have sex with men; HETERO—heterosexual contacts.

Figure 3

Phylogenetic analysis of subtype B sequences, N = 740. A phylogenetic tree of the pol region of subtype B sequences from 740 HIV-1 patients using the maximum likelihood (ML) with GTR + G + I model is shown. Included are three reference sequences (Table S1). The tree was visualized in Fig Tree version 1.4.4. Clusters (bootstrap values > 0.7) are colored in grey. Countries of origin are colored as follows: SSA (Sub-Saharan Africa) in navy blue; EEU/CA (Eastern Europe and Central Asia) in red; WCEU/NA (Western and Central Europe and North America) in orange; IL (Israel) in light green; other/unknown birthplace in turquoise; reference sequences in purple. PWID—people who use injection drug; MSM—men who have sex with men; HETERO—heterosexual contacts.

Figure 4

Phylogenetic analysis of subtype A sequences, N = 482. A phylogenetic tree of the pol region of subtype A sequences from 482 HIV-1 patients using the maximum likelihood (ML) with GTR + G + I model is shown. Included are three reference sequences (Table S1). The tree was visualized in Fig Tree version 1.4.4. Clusters (bootstrap values > 0.7) are colored in grey. Countries of origin are colored as follows: SSA (Sub-Saharan Africa) in navy blue; EEU/CA (Eastern Europe and Central Asia) in red; WCEU/NA (Western and Central Europe and North America) in orange; IL (Israel) in light green; other/unknown birthplace in turquoise; reference sequences in purple. The dashed line presents sub-subtype A6. PWID—people who use injection drug; MSM—men who have sex with men.