Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and syndromic treatment of men with urethral discharge in Kingston, Jamaica, 2018-19.

OBJECTIVES: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered. METHODS: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N. gonorrhoeae isolates (n = 96) using Etest and interpreted using CLSI criteria. RESULTS: The median age of the subjects was 28 years (range: 18-73 years) with a median of 2 sexual partners (range: 1-25) per male in the previous 3 months. All examined N. gonorrhoeae isolates were susceptible to ceftriaxone (96/96), azithromycin (91/91), cefixime (91/91) and spectinomycin (91/91). For ciprofloxacin and gentamicin, respectively, 98.9% (91/92) and 91.3% (84/92) of the isolates were susceptible and 1.1% (1/92) and 8.7% (8/92) showed intermediate susceptibility/resistance. For tetracycline and benzylpenicillin, respectively, 38.0% (35/92) and 22.0% (20/91) of the isolates were susceptible, 52.2% (48/92) and 74.7% (68/91) showed intermediate susceptibility/resistance and 9.8% (9/92) and 3.3% (3/91) were resistant. Syndromic treatment was administered as follows: 93.1% received 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline orally q12h for 1-2 weeks and 6.9% received 500 mg of ciprofloxacin orally plus 100 mg of doxycycline orally q12h for 1 week. CONCLUSIONS: Ceftriaxone (250 mg) remains appropriate for gonorrhoea treatment in the examined population of men in Kingston, Jamaica. Surveillance of N. gonorrhoeae AMR should be expanded in Jamaica and other Caribbean countries to guide evidence-based treatment guidelines.

A systematic review of the genetic mechanisms of dolutegravir resistance.

BACKGROUND: Characterizing the mutations selected by the integrase strand transfer inhibitor (INSTI) dolutegravir and their effects on susceptibility is essential for identifying viruses less likely to respond to dolutegravir therapy and for monitoring persons with virological failure (VF) on dolutegravir therapy. METHODS: We systematically reviewed dolutegravir resistance studies to identify mutations emerging under dolutegravir selection pressure, the effect of INSTI resistance mutations on in vitro dolutegravir susceptibility, and the virological efficacy of dolutegravir in antiretroviral-experienced persons. RESULTS AND CONCLUSIONS: We analysed 14 studies describing 84 in vitro passage experiments, 26 studies describing 63 persons developing VF plus INSTI resistance mutations on a dolutegravir-containing regimen, 41 studies describing dolutegravir susceptibility results, and 22 clinical trials and 16 cohort studies of dolutegravir-containing regimens. The most common INSTI resistance mutations in persons with VF on a dolutegravir-containing regimen were R263K, G118R, N155H and Q148H/R, with R263K and G118R predominating in previously INSTI-naive persons. R263K reduced dolutegravir susceptibility ∼2-fold. G118R generally reduced dolutegravir susceptibility >5-fold. The highest levels of reduced susceptibility occurred in viruses containing Q148 mutations in combination with G140 and/or E138 mutations. Dolutegravir two-drug regimens were highly effective for first-line therapy and for virologically suppressed persons provided dolutegravir's companion drug was fully active. Dolutegravir three-drug regimens were highly effective for salvage therapy in INSTI-naive persons provided one or more of dolutegravir's companion drugs was fully active. However, dolutegravir monotherapy in virologically suppressed persons and functional dolutegravir monotherapy in persons with active viral replication were associated with a non-trivial risk of VF plus INSTI resistance mutations.

Optimizing Interventions Across the HIV Care Continuum: A Case Study Using Process Improvement Analysis.

UNAIDS' 90-90-90 goal for 2020 is for 90% of HIV-infected people to know their status, 90% of infected individuals to receive antiretroviral therapy (ART), and 90% of those on ART to achieve viral suppression. To achieve these ambitious goals, effective care delivery programs are needed. In this paper we present a case study showing how HIV care can be improved by viewing the patient care process as a production process and applying methods of process improvement analysis. We examine the continuum of HIV care at a hospital-based HIV clinic in Kingston, Jamaica. We perform qualitative analysis to identify key programmatic, personnel, and clinical areas for process improvement. We then perform quantitative analysis. We develop a stochastic model of the care process which we use to evaluate the effects of potential process improvements on the number of patients who receive ART and the number who achieve viral suppression. We also develop a model for optimal investment of a fixed budget among interventions aimed at improving the care cascade and we use the model to determine the optimal investment among three interventions that the clinic could invest in. By viewing the patient care process as a production process and applying qualitative and quantitative process improvement analysis, our case study illustrates how clinics can identify the best ways to maximize clinical outcomes. Our methods are generalizable to other HIV care clinics as well as to clinics that provide care for other chronic conditions (e.g., diabetes, hepatitis B, or opioid use disorder).

HIV-1 transmitted drug resistance surveillance: shifting trends in study design and prevalence estimates.

INTRODUCTION: HIV-1 transmitted drug resistance (TDR) prevalence increased during the initial years of the antiretroviral therapy (ART) global scale-up. Few studies have examined recent trends in TDR prevalence using published genetic sequences and described the characteristics of ART-naïve persons from whom these published sequences have been obtained. METHODS: We identified 125 studies published between 2014 and 2019 for which HIV-1 reverse transcriptase (RT) with or without protease from ≥50 ART-naïve adult persons were submitted to the GenBank sequence database. The population characteristics and TDR prevalence were compared to those in 122 studies published in the preceding five years between 2009 and 2013. TDR prevalence was analysed using median study-level and person-level data. RESULTS AND DISCUSSION: The 2009 to 2013 and 2014 to 2019 studies reported sequence data from 32,866 and 41,724 ART-naïve persons respectively. Studies from the low- and middle-income country (LMIC) regions in sub-Saharan Africa, South/Southeast Asia and Latin America/Caribbean accounted for approximately two-thirds of the studies during each period. Between the two periods, the proportion of studies from sub-Saharan Africa and from South/Southeast Asia countries other than China decreased from 43% to 32% and the proportion of studies performed at sentinel sites for recent HIV-1 infection decreased from 33% to 22%. Between 2014 and 2019, median study-level TDR prevalence was 4.1% in South/Southeast Asia, 6.0% in sub-Saharan Africa, 9.1% in Latin America/Caribbean, 8.5% in Europe and 14.2% in North America. In the person-level analysis, there was an increase in overall, NNRTI and two-class NRTI/NNRTI resistance in sub-Saharan Africa; an increase in NNRTI resistance in Latin America/Caribbean, and an increase in overall, NNRTI and PI resistance in North America. CONCLUSIONS: Overall, NNRTI and dual NRTI/NNRTI-associated TDR prevalence was significantly higher in sub-Saharan Africa studies published between 2014 and 2019 compared with those published between 2009 and 2013. The decreasing proportion of studies from the hardest hit LMIC regions and the shift away from sentinel sites for recent infection suggests that global TDR surveillance efforts and publication of findings require renewed emphasis.

A comparison of younger and older men who have sex with men using data from Jamaica AIDS Support for Life: characteristics associated with HIV status.

Jamaica is home to over 10% of the Caribbean's HIV-positive population. Men who have sex with men (MSM) have a higher prevalence of HIV compared to the general public. Thus, the purpose of this study is to assess characteristics associated with HIV, such as condom use and number of sexual partners, comparing young, those aged 18-24, to older, aged 25 and older, MSM in Jamaica. We hypothesised, and found support for the notion, that younger MSM would have a lower rate of some risky behaviours associated with HIV seropositivity. Service data for 160 self-selected MSM aged 18-62, from Kingston, Jamaica were analysed. The majority identified as homosexual (compared to bisexual), over half of respondents completed a tertiary level of education (e.g. any post-high school training), and 59.1% were employed. Almost all participants reported agreeing to use a condom when requested (93.6%). Prevalence of HIV was 17.8%, much lower than the 32% found in national studies, and is likely an underestimation reflecting patterns of this self-selected sample. Additionally, over one-third reported experiencing sexual abuse. Statistically significant relationships were found between age group and tertiary education, employment status, condom use with a regular partner, and sexual abuse. Younger MSM were more likely to have been sexually abused and were more likely to always wear a condom with their regular partner. A limitation of this study was the extent of missing data, restricting generalisability. However, by acknowledging the heterogeneity of the Jamaican MSM population, and subsequently evaluating behaviours across age groups, nuances emerge which highlight behavioural diversity. Findings may inform public health practitioners in developing targeted interventions.

HIV treatment as prevention in Jamaica and Barbados: magic bullet or sustainable response?

This discursive article introduces HIV treatment as prevention (TasP) and identifies various models for its extrapolation to wider population levels. Drawing on HIV surveillance data for Jamaica and Barbados, the article identifies significant gaps in HIV response programming in relation to testing, antiretroviral treatment coverage, and treatment adherence, thereby highlighting the disparity between assumptions and prerequisites for TasP success. These gaps are attributable, in large part, to sociocultural impediments and structural barriers, severe resource constraints, declining political will, and the redefinition of HIV as a manageable, chronic health issue. Antiretroviral treatment and TasP can realize success only within a combination prevention frame that addresses structural factors, including stigma and discrimination, gender inequality and gender-based violence, social inequality, and poverty. The remedicalization of the response compromises outcomes and undermines the continued potential of HIV programming as an entry point for the promotion of sexual, health, and human rights.

HIV-1 drug resistance in treatment-naive chronically infected patients in Jamaica.

BACKGROUND: HIV-1 drug resistance in treatment-naive patients has a significant impact on the individual patient as well as implications for the wider population. These effects are amplified in the context of resource-limited settings, which are rapidly expanding access to antiretroviral therapy. METHODS: This cross-sectional survey at a single treatment site in Kingston, Jamaica was designed to identify the prevalence of HIV-1 drug-resistant mutations in chronically infected, treatment-naive patients. Mutations were identified using the Stanford HIV database algorithm and the World Health Organization (WHO) HIV Drug Resistance (HIVDR) surveillance mutations. RESULTS: The inclusion of 103 cases in the study resulted in 79 (76.6%) amplifiable samples. Genotype analysis revealed that 12.6% (95% CI 5.3, 19.9) were identified as having clinically significant mutations, while 10.1% (95% CI 3.5, 16.7) had WHO HIVDR surveillance mutations. CONCLUSIONS: According to the WHO standard, this study population has a moderate level of HIVDR in treatment-naive patients and strongly implies the need to introduce HIVDR surveillance in Jamaica.

Long-term antiretroviral treatment outcomes in seven countries in the Caribbean.

OBJECTIVES: To report long-term HIV treatment outcomes in 7 Caribbean countries. DESIGN: Observational cohort study. METHODS: We report outcomes for all antiretroviral therapy (ART) naive adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. RESULTS: A total of 8203 patients were on ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14-50 months). The overall mortality was 13%: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender [hazard ratio (HR), 1.58; 95% confidence interval (CI): 1.33 to 1.87], body weight (HR, 0.85 per 10 pounds; 95% CI: 0.82 to 0.89), hemoglobin (HR, 0.84 per g/dL; 95% CI: 0.80 to 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 to 0.93), concurrent tuberculosis (HR, 1.58; 95% CI: 1.25 to 2.01) and age (HR, 1.19 per 10 years; 95% CI: 1.11 to 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad, and Haiti was not significantly different. A total of 75% of patients remained alive and in care at the end of the study period. CONCLUSIONS: Long-term mortality rates vary widely across the Caribbean countries. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent tuberculosis. Earlier ART initiation will be critical to improve the outcomes.