A simple tool to evaluate the antiretroviral therapy programme in primary health care setting of Lesotho.

AIM: An evaluative tool for the antiretroviral therapy programme was developed for use in the primary health care setting of Lesotho. BACKGROUND: Information on processes followed in the development of standardized and acceptable evaluative tools is not always available to practicing nurses. METHODS: Behaviours affecting the antiretroviral therapy (ART) programme were contextualized using the conceptual model for social programmes and Intervention Wheel framework. A convergent parallel mixed-methods design was used to describe perceptions and explore experiences of nurses and patients. The Instrument Development Construct Validation process was used to develop an evaluative tool that was pre-tested on 17 respondents. Results were analysed using SPSS (23), and internal consistency using Cronbach's alpha coefficient was .768. RESULTS: The tool collects information on staffing patterns, services offered, patients seen, time spent seeking services, consultation time, Antiretroviral (ARV) availability, staff adequacy, staff competency, equipment adequacy, service efficiency, activity documentation, patient satisfaction, job satisfaction, monitoring and evaluation. CONCLUSIONS: The evaluative tool permits identification of factors affecting delivery of the ART programme, hence assisting nurses to improve services provided. IMPLICATIONS FOR NURSING MANAGEMENT: This method can be used to develop evaluative tools to assess implementation of public health services and inform successes, challenges and recognize improvement approaches.

Development and Validation of Surveillance-Based Algorithms to Estimate Hepatitis C Treatment and Cure in New York City.

CONTEXT: Treatment options for chronic hepatitis C virus (HCV) have improved in recent years. The burden of HCV in New York City (NYC) is high. Measuring treatment and cure among NYC residents with HCV infection will allow the NYC Department of Health and Mental Hygiene (DOHMH) to appropriately plan interventions, allocate resources, and identify disparities to combat the hepatitis C epidemic in NYC. OBJECTIVE: To validate algorithms designed to estimate treatment and cure of HCV using RNA test results reported through routine surveillance. DESIGN: Investigation by NYC DOHMH to determine the true treatment and cure status of HCV-infected individuals using chart review and HCV test data. Treatment and cure status as determined by investigation are compared with the status determined by the algorithms. SETTING: New York City health care facilities. PARTICIPANTS: A total of 250 individuals with HCV reported to the New York City Department of Health and Mental Hygiene (NYC DOHMH) prior to March 2016 randomly selected from 15 health care facilities. MAIN OUTCOME MEASURES: The sensitivity and specificity of the algorithms. RESULTS: Of 235 individuals successfully investigated, 161 (69%) initiated treatment and 96 (41%) achieved cure since the beginning of 2014. The treatment algorithm had a sensitivity of 93.2% (95% confidence interval [CI], 89.2%-97.1%) and a specificity of 83.8% (95% CI, 75.3%-92.2%). The cure algorithm had a sensitivity of 93.8% (95% CI, 88.9%-98.6%) and a specificity of 89.4% (95% CI, 83.5%-95.4%). Applying the algorithms to 68 088 individuals with HCV reported to DOHMH between July 1, 2014, and December 31, 2016, 28 392 (41.7%) received treatment and 16 921 (24.9%) were cured. CONCLUSIONS: The algorithms developed by DOHMH are able to accurately identify HCV treatment and cure using only routinely reported surveillance data. Such algorithms can be used to measure treatment and cure jurisdiction-wide and will be vital for monitoring and addressing HCV. NYC DOHMH will apply these algorithms to surveillance data to monitor treatment and cure rates at city-wide and programmatic levels, and use the algorithms to measure progress towards defined treatment and cure targets for the city.

Quality of antiretroviral and opportunistic infection medications dispensed from developing countries and Internet pharmacies.

WHAT IS KNOWN AND OBJECTIVE: Generic manufacturers help decrease the cost of antiretroviral (ARV) and antimicrobial medications which are used to treat opportunistic infections (OIs) in developing countries. Concerns have been expressed about potential quality issues with such medications as a result of the identification of numerous counterfeit medications in developing countries. However, few studies have assessed the quality of these medications using the United States Pharmacopeia (USP) compendial standards. The goal of this study was to assess the quality of ARV and OI medications obtained from various sources, including South Africa, United States, China, Ethiopia, Thailand, Laos, Mexico, Nigeria and five Internet pharmacies. METHODS: Zidovudine, lamivudine, efavirenz, nevirapine, isoniazid and sulfamethoxazole/trimethoprim tablets/capsules were obtained from eight countries and five Internet pharmacies. The tablets/capsules were separated into distinct samples, based on the drug's active ingredient, manufacturer and drug control number. Each distinct sample was analysed for drug content, dissolution, content uniformity and breaking force using USP 32-National Formulary 27 (USP 32-NF 27) compendial methods and compared to the USP standards. RESULTS AND DISCUSSION: A total of 2027 tablets/capsules were obtained with 88 distinct samples identified. All samples met the USP 32-NF 27 standards for drug content with a range of 92.7-108.6%. Six of the 88 samples failed the dissolution test by 1.5-8.3% below the standard range. Ninety-eight per cent of all 88 samples met the USP criteria for content uniformity based on weight variation. One sample of isoniazid was found to have a low breaking force of 2.8 kiloponds. The results of this study show that there were no problems with the samples of ARV and OI medications tested for drug quality from the specified locations. As there are many studies and reports that discuss the poor quality of generic medications with only a few assessing drug quality, the implications of this study's results are to: (i) help better understand patient outcomes; (ii) help patients gain access to beneficial medications for HIV and OIs; and (iii) ensure an overall increase in access to medications where needed. WHAT IS NEW AND CONCLUSION: This study is one of the largest to date concerning medication type and sample size for the assessment of ARV and OI medications using drug content as a measure of quality. The samples were obtained from more diverse geographical locations compared to previous studies and, for the first time, included Internet pharmacies. In addition to drug content, this study evaluated a more complete quality profile including dissolution, content uniformity and breaking force. This study showed that drug quality should be assessed consistently in order to better identify counterfeit medications compared to current assessments and that there should be uniform guidelines for how to assess quality.

Cost-effectiveness analysis along the continuum of HIV care: how can we optimize the effect of HIV treatment as prevention programs?

The cascade of HIV care has been proposed as a useful tool to monitor health system performance across the key stages of HIV care delivery to reduce morbidity, mortality, and HIV transmission, the focal points of HIV Treatment as Prevention campaigns. Interventions to improve the cascade at its various stages may vary substantially in their ability to deliver health value per amount expended. In order to meet global antiretroviral treatment access targets, there is an urgent need to maximize the value of health spending by prioritizing cost-effective interventions. We executed a literature review on economic evaluations of interventions to improve specific stages of the cascade of HIV care. In total, 33 articles met the criteria for inclusion in the review, 22 (67 %) of which were published within the last 5 years. Nonetheless, substantial gaps in our knowledge remain, particularly for interventions to improve linkage and retention in HIV care in developed and developing-world settings and generalized and concentrated epidemics. We make the case here that the attention of scientists and policymakers needs to turn to the development, implementation, and rigorous evaluation of interventions to improve the various stages of the cascade of HIV care.

Quality of antiretroviral therapy in public health facilities in Nigeria and perceptions of end users.

AIM: This paper describes perceptions of the end users on quality of antiretroviral therapy (ART) in public health facilities in Nigeria. BACKGROUND: Health care services in Nigeria face challenges of meeting end users' requirements and expectations for quality ART service provision. METHOD: A qualitative design was followed. Unstructured focus group discussions were conducted with end users (n = 64) in six locations across the six geopolitical zones of Nigeria. RESULTS: The findings indicate that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. CONCLUSION: End users expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV. IMPLICATIONS FOR NURSING MANAGEMENT: A best practice guideline for the provision of end user focused ART service provision was developed for nurse managers.

The Suboptimal Pediatric HIV Viral Load Cascade: Multidistrict Cohort Study Among Children Taking Antiretroviral Therapy in Lesotho, Southern Africa.

BACKGROUND: Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. METHODS: In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. RESULTS: In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. CONCLUSIONS: Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

First Extended-Release Injectable Drug Therapy for HIV.

Cabenuva-an injectable formulation of cabotegravir and rilpivirine and the first injectable complete therapy for adults with HIV-1-is now approved.It is administered once a month as two intramuscular injections following a month of treatment with the oral forms of these drugs.

The relationship of CCR5 antagonists to CD4+ T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIV-infected patients.

PURPOSE: Lower CD4+ T-cell counts are related to increased morbidity and mortality despite virologic suppression. CCR5 antagonists are associated with robust CD4+ T-cell responses. We examined the relationship of CCR5 antagonists to CD4+ T-cell gains. DESIGN: Meta-regression of recent phase 2-3 trials evaluating new antiretroviral agents in treatment-experienced subjects. METHODS: We analyzed the relationship of CCR5 antagonists to CD4+ T-cell count increase 24 weeks after initiating the new regimen using a linear model with generalized estimating equations controlling for differing rates of virologic suppression. Each treatment group was treated as a data point weighted by sample size. RESULTS: We included 46 treatment groups from 17 trials (11 groups from 5 trials used CCR5 antagonists). Controlling for average baseline HIV-1 RNA and proportion of subjects achieving HIV-1 RNA <50 copies/mL, use of a CCR5 antagonist was associated with an additional significant CD4+ T-cell gain of +30/µL (95% CI, 19-42) at 24 weeks compared to treatment groups not using a CCR5 antagonist. CONCLUSIONS: Use of a CCR5 antagonist was associated with an enhanced CD4+ T-cell count response independent of virologic suppression. This observation supports further evaluation of CCR5 antagonists in patients with discordant immunologic and virologic responses to ART.

Antiretroviral Stewardship: A Review of Published Outcomes with Recommendations for Program Implementation.

Persons living with HIV (PLWHs) are at high risk for medication errors when hospitalized, but antiretroviral medications are not often evaluated by antimicrobial stewardship programs (ASPs) because they are not specifically discussed in the standards of practice. However, antiretroviral (ARV) stewardship programs (ARVSPs) have been shown to decrease medication error rates and improve other outcomes. The goal of this article is to review published literature on ARVSPs and provide guidance on key aspects of ARVSPs. A MEDLINE search using the term "antiretroviral stewardship" was conducted. Original research articles evaluating ARVSPs in hospitalized, adult PLWHs were included. Six original research articles evaluating unique inpatient ARVSPs met inclusion criteria. All 6 studies evaluating medication errors as the primary outcome found a significant reduction in errors in the postimplementation phase. Based on current standards for ASPs, we propose core elements for ARVSPs. Future organizational guidelines for antimicrobial stewardship should include official recommendations for ARV medications.

Identifying appropriate candidates for long-acting antiretroviral therapy: findings from a survey of health care providers in the ATLAS-2M trial.

INTRODUCTION: Recent results from Phase 3 clinical trials with cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) have shown that a monthly regimen is non-inferior to daily oral antiretroviral therapy (ART). Additional insights are necessary to prepare for LA ART roll-out, including identifying the appropriate patients. METHODS: Within the ATLAS-2M trial, an online survey was administered to 329 health care providers (HCPs) in 13 countries. Multivariate logistic regression was conducted to identify factors associated with providers considering a greater proportion of patients as appropriate LA ART candidates. RESULTS: Forty-seven percent of HCPs believed that "some" patients (25-50%) would be appropriate while nearly one-quarter of HCPs (23%) felt that "many" patients (more than 50%) would be appropriate candidates for LA ART. Providers in the African region had a greater odds of identifying a greater proportion of their patients as appropriate candidates (AOR 8.97; p < 0.001) vs. other regions. Nurses/physician assistants and research staff/pharmacists had a higher odds of perceiving a greater proportion of their patients as appropriate candidates vs. physicians, respectively (AOR 3.42 p < 0.001; AOR 2.48; p = 0.19). Providers who had experience transitioning patients from LA to oral ART had a higher odds of reporting that more of their patients would be appropriate candidates (AOR 1.64; p = 0.008) vs. those without experience. CONCLUSION: A significant proportion of providers reported that many of their patients would be appropriate candidates for LA ART. To optimize roll-out after regulatory approval, it is important to support providers with tools to help identify patients who would most benefit from this option.

Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity.

OBJECTIVE: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen. DESIGN: Prospective 36 months cohort study of patients switched to zidovudine/stavudine plus didanosine plus lopinavir/ritonavir capsules as second-line regimen. METHODOLOGY: Structured interview, medical examination, and laboratory assessment performed every 6 months. RESULTS: We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+ count at baseline was 108 cell/microL, median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%) had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At month 36, 82% of the patients achieved viral suppression (<400 copies/ mL) and the median increase in CD4+ count was 214 cell/microL, (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. CONCLUSIONS: Our study confirms lopinavir/ ritonavir-based second-line regimen but with a high rate of toxicities.

Methodological standards in non-inferiority AIDS trials: moving from adherence to compliance.

BACKGROUND: The interpretation of the results of active-control trials regarding the efficacy and safety of a new drug is important for drug registration and following clinical use. It has been suggested that non-inferiority and equivalence studies are not reported with the same quantitative rigor as superiority studies. METHODS: Standard methodological criteria for non-inferiority and equivalence trials including design, analysis and interpretation issues were applied to 18 recently conducted large non-inferiority (15) and equivalence (3) randomized trials in the field of AIDS antiretroviral therapy. We used the continuity-corrected non-inferiority chi-square to test 95% confidence interval treatment difference against the predefined non-inferiority margin. RESULTS: The pre-specified non-inferiority margin ranged from 10% to 15%. Only 4 studies provided justification for their choice. 39% of the studies (7/18) reported only intent-to-treat (ITT) analysis for the primary endpoint. When on-treatment (OT) and ITT statistical analyses were provided, ITT was favoured over OT for results interpretation for all but one study, inappropriately in this statistical context. All but two of the studies concluded there was "similar" efficacy of the experimental group. However, 9/18 had inconclusive results for non-inferiority. CONCLUSION: Conclusions about non-inferiority should be drawn on the basis of the confidence interval analysis of an appropriate primary endpoint, using the predefined criteria for non-inferiority, in both OT and ITT, in compliance with the non-inferiority and equivalence CONSORT statement. We suggest that the use of the non-inferiority chi-square test may provide additional useful information.

[WHO program for prequalification of antiretroviral, antimalarial and antituberculosis drugs]. / Programme oms de pré-qualification des antirétroviraux, antipaludiques et antituberculeux.

Partnered with UNICEF, UNAIDS and the UN Population Fund, and receiving support from the World Bank, the WHO Prequalification Programme provides a solid, scientific assessment of the quality of both generic and patented medicines, based on internationally harmonized standards for evaluating information on product quality and bioequivalence, inspecting manufacturing sites, and undertaking quality control of pharmaceutical production. Agencies and organizations who procure medicines can be assured that products prequalified by WHO are of proven quality and that they do not themselves have to test these products. The WHO list of prequalified products also means that agencies procuring medicines can choose between several manufacturers offering the same quality product, which offers scope for negotiating lower prices. As a result of this Programme, capacity to manufacture generic products of assured quality is increasing, as is capacity to monitor that quality. Initially focusing on medicines for HIV/AIDS, TB and malaria, the Programme is now being expanded to also cover medicines for reproductive health.

The global status of resistance to antiretroviral drugs.

Since 1989, the emergence of resistant human immunodeficiency virus mutants has been documented for any new antiretroviral agent introduced in the clinical setting; it is a major cause of failure of antiretroviral therapy that may ultimately compromise the antiretroviral's efficacy in the general population. In most cases, resistance is due to poor adherence by the patient and/or to low potency of the therapeutic regimen. Resistance is called "primary" if detected in treatment-naive persons and is called "acquired" when it develops in treatment-experienced persons. This latter population represents potential transmitters of resistant viruses to newly infected persons. Data about the actual prevalence of resistance are derived from studies that differ in design, sample size, geographic area, and definitions. For this reason, a limited number of surveillance programs have been established in the past, both in countries where highly active antiretroviral therapy is widely accessible and in geographic areas where it is being introduced.

A quantitative basis for antiretroviral therapy for HIV-1 infection.

Highly active antiretroviral therapy (HAART) has dramatically decreased mortality from HIV-1 infection and is a major achievement of modern medicine. However, there is no fundamental theory of HAART. Elegant models describe the dynamics of viral replication, but a metric for the antiviral activity of drug combinations relative to a target value needed for control of replication is lacking. Treatment guidelines are based on empirical results of clinical trials in which other factors such as regimen tolerability also affect outcome. Why only certain drug combinations control viral replication remains unclear. Here we quantify the intrinsic antiviral activity of antiretroviral drug combinations. We show that most single antiretroviral drugs show previously unappreciated complex nonlinear pharmacodynamics that determine their inhibitory potential at clinical concentrations. We demonstrate that neither of the major theories for drug combinations accurately predicts the combined effects of multiple antiretrovirals. However, the combined effects can be understood with a new approach that considers the degree of independence of drug effects. This analysis allows a direct comparison of the inhibitory potential of different drug combinations under clinical concentrations, reconciles the results of clinical trials, defines a target level of inhibition associated with treatment success and provides a rational basis for treatment simplification and optimization.