A Nearly 50% Decrease in New HIV Diagnoses in Rhode Island from 2006-2016: Implications for Policy Development and Prevention.

In the last decade, reductions in HIV incidence have been observed across the United States. However, HIV continues to disproportionately impact gay, bisexual, and other men who have sex with men (MSM). In Rhode Island, rates of HIV diagnoses have decreased by 44% across all groups over the last decade. This success has been the result of close collaboration across multiple sectors. Different prevention approaches, including syringe exchange programs, community-based HIV testing, condom distribution, HIV care and treatment, and pre-exposure prophylaxis (PrEP) have all contributed to the decline in HIV diagnoses across the state. In 2015, Rhode Island became one of the first states to sign on to the Joint United Nations Programme on HIV/AIDS "90-90-90" campaign to end the HIV epidemic by 2030. Intensified and innovative initiatives are needed to improve progress in HIV prevention and treatment, especially in populations who are most at risk.

Clinical Benefits and Cost-Effectiveness of Laboratory Monitoring Strategies to Guide Antiretroviral Treatment Switching in India.

Current Indian guidelines recommend twice-annual CD4 testing to monitor first-line antiretroviral therapy (ART), with a plasma HIV RNA test to confirm failure if CD4 declines, which would prompt a switch to second-line ART. We used a mathematical model to assess the clinical benefits and cost-effectiveness of alternative laboratory monitoring strategies in India. We simulated a cohort of HIV-infected patients initiating first-line ART and compared 11 strategies with combinations of CD4 and HIV RNA testing at varying frequencies. We included adaptive strategies that reduce the frequency of tests after 1 year from 6 to 12 months for virologically suppressed patients. We projected life expectancy, time on failed first-line ART, cumulative 10-year HIV transmissions, lifetime cost (2014 US dollars), and incremental cost-effectiveness ratios (ICERs). We defined strategies as cost-effective if their ICER was <1 × the Indian per capita gross domestic product (GDP, $1,600). We found that the current Indian guidelines resulted in a per person life expectancy (from mean age 37) of 150.2 months and a per person cost of $2,680. Adding annual HIV RNA testing increased survival by ∼8 months; adaptive strategies were less expensive than similar nonadaptive strategies with similar life expectancy. The most effective strategy with an ICER <1 × GDP was the adaptive HIV RNA strategy (ICER $840/year). Cumulative 10-year transmissions decreased from 27.2/1,000 person-years with standard-of-care to 20.9/1,000 person-years with adaptive HIV RNA testing. In India, routine HIV RNA monitoring of patients on first-line ART would increase life expectancy, decrease transmissions, be cost-effective, and should be implemented.

Addressing the increasing burden of sexually transmitted infections in Rhode Island.

The rates of sexually transmitted infections (STI) including chlamydia, gonorrhea, and syphilis, are increasing across the United States, including in Rhode Island (RI). These STIs affect many otherwise healthy adolescents and young adults, and represent a significant source of morbidity. The Centers for Disease Control and Prevention encourages states to develop strategies for addressing increasing STI rates in the setting of diminishing public health resources. The RI Department of Health (DOH) works with providers and funded community- based organizations to promote STI screening, expedited partner therapy, and partner services to reduce STI rates. The Miriam Hospital Immunology Center opened a public HIV/STI Clinic, which offers free and confidential testing for HIV, viral hepatitis, chlamydia, gonorrhea, and syphilis, as well as post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) services to prevent HIV. In collaboration with the RI DOH, the Clinic serves as a referral source across the state for complicated STI cases.

Clinical impact and cost-effectiveness of expanded voluntary HIV testing in India.

BACKGROUND: Despite expanding access to antiretroviral therapy (ART), most of the estimated 2.3 to 2.5 million HIV-infected individuals in India remain undiagnosed. The questions of whom to test for HIV and at what frequency remain unclear. METHODS: We used a simulation model of HIV testing and treatment to examine alternative HIV screening strategies: 1) current practice, 2) one-time, 3) every five years, and 4) annually; and we applied these strategies to three population scenarios: 1) the general Indian population ("national population"), i.e. base case (HIV prevalence 0.29%; incidence 0.032/100 person-years [PY]); 2) high-prevalence districts (HIV prevalence 0.8%; incidence 0.088/100 PY), and 3) high-risk groups (HIV prevalence 5.0%; incidence 0.552/100 PY). Cohort characteristics reflected Indians reporting for HIV testing, with a median age of 35 years, 66% men, and a mean CD4 count of 305 cells/µl. The cost of a rapid HIV test was $3.33. Outcomes included life expectancy, HIV-related direct medical costs, incremental cost-effectiveness ratios (ICERs), and secondary transmission benefits. The threshold for "cost-effective" was defined as 3x the annual per capita GDP of India ($3,900/year of life saved [YLS]), or for "very cost-effective" was <1x the annual per capita GDP ($1,300/YLS). RESULTS: Compared to current practice, one-time screening was very cost-effective in the national population (ICER: $1,100/YLS), high-prevalence districts (ICER: $800/YLS), and high-risk groups (ICER: $800/YLS). Screening every five years in the national population (ICER: $1,900/YLS) and annual screening in high-prevalence districts (ICER: $1,900/YLS) and high-risk groups (ICER: $1,800/YLS) were also cost-effective. Results were most sensitive to costs of care and linkage-to-care. CONCLUSIONS: In India, voluntary HIV screening of the national population every five years offers substantial clinical benefit and is cost-effective. Annual screening is cost-effective among high-risk groups and in high-prevalence districts nationally. Routine HIV screening in India should be implemented.

Adherence to HIV treatment and care among previously homeless jail detainees.

HIV-infected persons entering the criminal justice system (CJS) often experience suboptimal healthcare system engagement and social instability, including homelessness. We evaluated surveys from a multisite study of 743 HIV-infected jail detainees prescribed or eligible for antiretroviral therapy (ART) to understand correlates of healthcare engagement prior to incarceration, focusing on differences by housing status. Dependent variables of healthcare engagement were: (1) having an HIV provider, (2) taking ART, and (3) being adherent (≥95% of prescribed doses) to ART during the week before incarceration. Homeless subjects, compared to their housed counterparts, were significantly less likely to be engaged in healthcare using any measure. Despite Ryan White funding availability, insurance coverage remains insufficient among those entering jails, and having health insurance was the most significant factor correlated with having an HIV provider and taking ART. Individuals interfacing with the CJS, especially those unstably housed, need innovative interventions to facilitate healthcare access and retention.

Planning for success predicts virus suppressed: results of a non-controlled, observational study of factors associated with viral suppression among HIV-positive persons following jail release.

In the United States, jail frequently disrupts access to HIV care. EnhanceLink, a 10-site demonstration project promoting linkage to HIV primary care upon jail discharge, offered an opportunity to gauge how many releasees had favorable clinical outcomes. Individual level data were available on 1270 participants. Persons never discharged from the correctional environment were excluded. Multivariate logistic regression identified factors associated with viral suppression 6 months post discharge (6M-VL < 400). Among 1082 individuals eligible for follow-up evaluation, 25.7 % had 6M-VL < 400. 6M-VL < 400 was associated with case managers assessing whether help was needed for linkage to HIV-related medical services and clients keeping an appointment with a case manager. The adjusted odds ratio (aOR) of 6M-VL < 400 associated with attending a meeting with an HIV care provider within 30 days of release was 1.85. The results of this non-controlled, observational study support further development and rigorous evaluation of transitional care programs for HIV-positive jailed persons across the country.

HIV-positive and in jail: race, risk factors, and prior access to care.

UNLABELLED: Black individuals represent 13 % of the US population but 46 % of HIV positive persons and 40 % of incarcerated persons. The national EnhanceLink project evaluated characteristics of HIV-positive jail entrants at ten sites and explored associations between race and HIV disease state. Between 1/2008 and 10/2011, 1,270 study participants provided demographic and clinical data. Adjusted odds ratios (aORs) were calculated for advanced HIV disease (CD4 < 200 cells/mm(3)) and uncontrolled viremia (viral load > 400 copies/ml) for Black (n = 807) versus non-Black (n = 426) participants. Sixty-five percent of HIV-positive jail participants self-identified as Black. Among all participants, fewer than half had a high school diploma or GED, the median number of lifetime arrests was 15, and major mental illness and substance abuse were common. Black participants were more likely to be older than non-Black participants, and less likely to have health insurance (70 vs 83 %) or an HIV provider (73 vs 81 %) in the prior 30 days. Among all male study participants (n = 870), 20 % self-identified as homosexual or bisexual. Black male participants were more likely to be homosexual or bisexual (22 vs 16 %) and less likely to have a history of injection drug use (20 vs 50 %) than non-Black male participants. Advanced HIV disease was associated with self-identification as Black (aOR = 1.84, 95 % CI 1.16-2.93) and time since HIV diagnosis of more than two years (aOR = 3.55, 95 % CI 1.52-8.31); advanced disease was inversely associated with age of less than 38 years (aOR = 0.41, 95 % CI 0.24-0.70). Uncontrolled viremia was inversely associated with use of antiretroviral therapy (ART) in the prior 7 days (aOR = 0.25, 95 % CI 0.15-0.43) and insurance coverage in the prior 30 days (aOR = 0.46, 95 % CI 0.26-0.81). CONCLUSIONS: The racial disparities of HIV and incarceration among Black individuals in the US are underscored by the finding that 65 % of HIV-positive jail participants self-identified as Black in this ten-site study. Our study also found that 22 % of Black male participants self-identified as men who have sex with men (MSM). We believe these findings support jails as strategic venues to reach heterosexual, bisexual, and homosexual HIV-positive Black men who may have been overlooked in the community. Among HIV-positive jail entrants, Black individuals had more advanced HIV disease. Self-identification as Black was associated with a lower likelihood of having health insurance or an HIV provider prior to incarceration. HIV care and linkage interventions are needed within jails to better treat HIV and to address these racial disparities.

Integration of buprenorphine/naloxone treatment into HIV clinical care: lessons from the BHIVES collaborative.

BACKGROUND: Replication of effective practices requires detailed descriptions of implementation processes, barriers and facilitators, and lessons learned. The experiences of physicians leading the Buprenorphine HIV Evaluation and Support initiative provides valuable information for other HIV providers seeking to integrate medication-assisted treatment services into HIV clinical care. METHODS: Evaluation staff conduced site visits to the 10 funded Buprenorphine HIV Evaluation and Support programs to better understand buprenorphine/naloxone (bup/nx) integration practices; services offered; staffing; provider experiences with and perceptions of bup/nx; perceived barriers, facilitators, and sustainability; and recommendations regarding replication of integrated care program components. Interviews with site principal investigators conducted during the last year of program implementation were transcribed, coded, and analyzed according to both pre-identified and emerging themes. RESULTS: Integrated bup/nx and HIV treatment was successfully introduced to community and hospital-based clinics under the direction of infectious disease, psychiatry, and general internal medicine physicians. All but 1 of the principal investigators interviewed were highly satisfied with integrated HIV and bup/nx treatment, and all anticipated continued provision of the service. Multiple prescribers were necessary to ensure sufficient coverage and a bup/nx coordinator (eg, nurse, counselor) was seen as essential to the provision of quality care. Ongoing challenges included multisubstance use and mental health issues among patients; limited adoption of bup/nx treatment among colleagues; and the necessity of incorporating new procedures, including urine toxicology testing into established practice. CONCLUSIONS: Findings suggest that integrated bup/nx treatment and HIV care is acceptable to providers and feasible in a variety of practice settings.

Cost-effectiveness of HIV testing referral strategies among tuberculosis patients in India.

BACKGROUND: Indian guidelines recommend routine referral for HIV testing of all tuberculosis (TB) patients in the nine states with the highest HIV prevalence, and selective referral for testing elsewhere. We assessed the clinical impact and cost-effectiveness of alternative HIV testing referral strategies among TB patients in India. METHODS AND FINDINGS: We utilized a computer model of HIV and TB disease to project outcomes for patients with active TB in India. We compared life expectancy, cost, and cost-effectiveness for three HIV testing referral strategies: 1) selective referral for HIV testing of those with increased HIV risk, 2) routine referral of patients in the nine highest HIV prevalence states with selective referral elsewhere (current standard), and 3) routine referral of all patients for HIV testing. TB-related data were from the World Health Organization. HIV prevalence among TB patients was 9.0% in the highest prevalence states, 2.9% in the other states, and 4.9% overall. The selective referral strategy, beginning from age 33.50 years, had a projected discounted life expectancy of 16.88 years and a mean lifetime HIV/TB treatment cost of US$100. The current standard increased mean life expectancy to 16.90 years with additional per-person cost of US$10; the incremental cost-effectiveness ratio was US$650/year of life saved (YLS) compared to selective referral. Routine referral of all patients for HIV testing increased life expectancy to 16.91 years, with an incremental cost-effectiveness ratio of US$730/YLS compared to the current standard. For HIV-infected patients cured of TB, receiving antiretroviral therapy increased survival from 4.71 to 13.87 years. Results were most sensitive to the HIV prevalence and the cost of second-line antiretroviral therapy. CONCLUSIONS: Referral of all patients with active TB in India for HIV testing will be both effective and cost-effective. While effective implementation of this strategy would require investment, routine, voluntary HIV testing of TB patients in India should be recommended.

Lessons learned from a training collaboration between an Ivy League institution and a historically Black university.

The Miriam Hospital, Brown Medical School, and Jackson State University developed a joint training program for predoctoral, Black psychology students under the auspices of a training grant funded by the National Institutes of Health. The students in the program at Jackson State University had unlimited access to the clinical research resources and mentoring expertise at Brown Medical School. This innovative program began in 2001 and addresses the need for Black leaders in clinical research and academia who will focus on HIV and other infections that disproportionately affect the Black community. This collaboration has served as a bridge between an Ivy League institution and a historically Black university for training in clinical research to develop successful minority academicians.

Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients.

To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy.

BACKGROUND: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. OBJECTIVE: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. METHODS: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. RESULTS: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. CONCLUSIONS: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.

Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India.

OBJECTIVE: To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India. METHODS: Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database. RESULTS: All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%). CONCLUSION: The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.

The changing natural history of HIV disease: before and after the introduction of generic antiretroviral therapy in southern India.

The number of individuals seeking treatment for infection with human immunodeficiency virus increased as the cost of highly active antiretroviral therapy (HAART) decreased 20-fold after the introduction of generic HAART in India in the year 2000. The incidence of tuberculosis and opportunistic infections decreased to <2 cases per 100 person-years. Death rates decreased from 25 to 5 deaths per 100 person-years between 1997 and 2003.

Total lymphocyte count (TLC) is a useful tool for the timing of opportunistic infection prophylaxis in India and other resource-constrained countries.

BACKGROUND: In most resource-constrained countries, CD4 cell count testing is prohibitively expensive for routine clinical use and is not widely available. As a result, physicians are often required to make decisions about opportunistic infection (OI) chemoprophylaxis without a laboratory evaluation of HIV stage and level of immunosuppression. OBJECTIVES To evaluate the correlation of total lymphocyte count (TLC), an inexpensive and widely available parameter, to CD4 count. To determine a range of TLC cutoffs for the initiation of OI prophylaxis that is appropriate for resource-constrained settings. METHODS: Spearman correlation between CD4 count and TLC was assessed in patients attending an HIV/AIDS clinic in South India. Positive predictive value (PPV), negative predictive value (NPV), and sensitivity and specificity of various TLC cutoffs were computed for CD4 count <200 cells/mm3 and <350 cells/mm3. Correlation and statistical indices computed for all patients and for patients dually infected with HIV and active tuberculosis. RESULTS: High degree of correlation was noted between 650 paired CD4 and TLC counts (r = 0.744). TLC <1400 cells/mm3 had a 76% PPV, 86% NPV, and was 73% sensitive, 88% specific for CD4 count <200 cells/mm3. TLC <1700 cells/mm3 had a 86% PPV, 69% NPV, and was 70% sensitive, 86% specific for CD4 count <350 cells/mm3. The cost of a single CD4 count in India is approximately 30 US dollars, whereas the cost of a single TLC is 0.80 US dollars. CONCLUSION: TLC could serve as a low-cost tool for determining both a patient's risk of OI and when to initiate prophylaxis in resource-constrained settings. PPV, NPV, sensitivity, and specificity maximally aggregated at TLC <1400 cells/mm3 for CD4 <200 cell/mm3 and TLC <1700 cells/mm3 for CD4 <350 cells/mm3. Selection of appropriate TLC cutoffs for prophylaxis administration should be made on a regional basis depending on OI incidence, antimicrobial resistance patterns, and availability of the antimicrobials.