Evaluation of self-directed specimen collection for chlamydia and gonorrhea testing among people who use drugs.

Background: People who use drugs (PWUD) often have elevated sexually transmitted infection (STI) risk and unmet healthcare needs. Self-directed STI specimen collection (i.e., individuals collect the specimen and mail to the laboratory) may be valuable in addressing STI testing barriers among PWUD. Methods: Within a cohort study among PWUD in New York City, we conducted a cross-sectional substudy from November 2021-August 2022 assessing sexual health with a one-time online survey (n = 120); participants could opt-in to receive a self-collection kit. Participants who opted-in were mailed a kit containing collection materials (males: urine cup, females: vaginal swab), pre-paid return label, instructions, and educational information. Specimens were sent to the laboratory and tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). We measured the number of kits requested, delivered, mailed to the lab, and CT/GC positive; and examined differences in requesting a kit by sociodemographic and behavioral characteristics. Results: Sixty-three total kits were requested by 44 unique participants. Of the 63 requested, 41 were delivered; one kit was undeliverable at the provided address and the rest were not sent due to no address provided or being duplicate requests. Of the 41 kits delivered, three participants returned the kit to the lab; of those, one was positive for CT and GC. The greatest differences in those who did and did not request a kit were observed by age, sexual orientation, past-year sex trade and casual partnerships, and experiences of relationship violence. Conclusions: Self-directed specimen collection may be desirable for PWUD, but research is needed to understand barriers to this testing approach for this population.

Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women.

BACKGROUND: Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC). METHODS: GALT specimens from the terminal ileum, splenic flexure and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/ml. Flow cytometry, drug concentrations, and HIV RNA and DNA were analysed in tissue. CD4/8+ T-cells were tested for γδ TCR, and markers of T-cell activation and exhaustion. Data are reported as median (Q1-Q3). RESULTS: A total of 15 men and 5 women were enrolled. There was no difference in time since HIV diagnosis for those on RTG (9.5 [4-22] years) and DTG (17 [1-24] years; P=0.6), although time on RTG (5.4 [2.3-6.7] years) was greater than DTG (1.0 [0.1-1.5] years; P<0.001). Concentrations of RTG and DTG in rectal tissue were similar to previous reports: median tissue:plasma ratio was 11.25 for RTG and 0.44 for DTG. RNA:DNA ratios were 1.14 (0.18-5.10) for the RTG group and 0.90 (0.30-18.87) for the DTG group (P=0.95). No differences (P≥0.1) between CD4+ and CD8+ T-cell markers were found. CONCLUSIONS: RTG produced higher tissue exposures than DTG, but no significant differences in GALT HIV RNA, DNA or most immunological markers were observed. ClinicalTrials.gov NCT02218320.

Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study.

BACKGROUND: An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral and Nutrition (BAN) Study was performed to describe drug exposure and antiviral response. METHODS: Women using Combivir(®) (zidovudine [ZDV] + lamivudine [3TC]) +Aluvia(®) (lopinavir/ritonavir [LPV/RTV]) were enrolled. Breast milk (BM), mother plasma (MP) and infant plasma (IP) samples were obtained over 6 h after observed dosing at 6, 12 or 24 weeks post-partum for drug concentrations and HIV RNA. RESULTS: A total of 30 mother/infant pairs (10 each at 6, 12 and 24 weeks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, respectively, whereas LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24 weeks. The majority (98.3%) of BM concentrations were >HIV(wt) IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. CONCLUSIONS: ZDV and 3TC concentrated in BM whereas LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low antiretroviral concentrations in IP suggest prevention of transmission while breastfeeding may be due to antiretroviral effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.

Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007.

BACKGROUND: Transmitted drug resistance (TDR) limits antiretroviral options and thus complicates the management of HIV-positive patients. HIV disproportionately affects the southern US, but available national estimates of TDR prevalence principally reflect large metropolitan centres outside this region. METHODS: The Duke/UNC Acute HIV Program has collected data on acute or recent HIV infections (ARHI) in North Carolina since 1998. Acute infections represent antibody-negative, RNA-positive patients. Recent infection was determined by history of HIV testing or concordance between detuned ELISA and antibody avidity assays. Genotypic sequence data from the earliest collected pretreatment plasma samples were analysed with the Stanford HIV Database and screened for surveillance drug resistance mutations (SDRMs). RESULTS: A total of 253 individuals with ARHI between May 1998 and May 2007 had complete genotypic sequence data for analysis; 39.5% were acute infections, 78.7% were male, 64.8% were non-White and 53.8% were men who have sex with men. The overall prevalence of TDR was 17.8%, with SDRMs for non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) in 9.5% of the cohort. Mutations for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) were detected in 7.5% and for protease inhibitors (PIs) in 3.2%. K103N was the most common mutation (7.5%). Thymidine analogue mutations were found in 4.7% of samples; the most common PI SDRM was L90M (2.4%). Dual- or triple-class antiretroviral resistance was rare, encountered in only six (2.4%) samples. CONCLUSIONS: The prevalence of TDR in North Carolina is similar to estimates from the US metropolitan areas. These findings have implications for initial regimen selection and secondary prevention efforts outside of large, metropolitan HIV epicentres.