National Antiretroviral Therapy Program Research Articles

Retention in care among people living with HIV in the national antiretroviral therapy programme in Guinea: A retrospective cohort analysis.

Few studies have investigated retention in HIV care in West Africa. We measured retention in antiretroviral therapy (ART) programmes among people living with HIV and re-engagement in care among those lost to follow up (LTFU) in Guinea and identified associated risk factors using survival analysis. Patient-level data were analysed from 73 ART sites. Treatment interruptions and LTFU were defined as missing a ART refill appointment by over 30 days and by over 90 days respectively. A total of 26,290 patients initiating ART between January 2018 and September 2020 were included in the analysis. The mean age at ART initiation was of 36.2 years, with women accounting for 67% of the cohort. Retention 12 months after ART initiation was 48.7% (95%CI 48.1-49.4%). The LTFU rate was 54.5 per 1000 person-months (95% CI 53.6-55.4), with the peak hazards of LTFU occurring after the first visit and decreasing steadily over time. In an adjusted analysis, the hazards of LTFU were higher among men compared to women (aHR = 1.10; 95%CI 1.08-1.12), being aged 13-25 years old versus older patients (aHR = 1.07; 95%CI = 1.03-1.13), and among those initating ART in smaller health facilities (aHR = 1.52; 95%CI 1.45-1.60). Among 14,683 patients with an LTFU event, 4,896 (33.3%) re-engaged in care, of whom 76% did so within six months from LTFU. The re-engagement rate was 27.1 per 1000 person-months (95%CI 26.3-27.9). Treatment interruptions were correlated with rainfall patterns and end of year mobility patterns. Rates of retention and re-engagement in care are very low in Guinea, undermining the effectiveness and durability of first-line ART regimens. Tracing interventions and differentiated service delivery of ART, including multi-month dispensing may improve care engagement, especially in rural areas. Further research should investigate social and health systems barriers to retention in care.

To what extent were life expectancy gains in South Africa attributable to declines in HIV/AIDS mortality from 2006 to 2017? A life table analysis of age-specific mortality

In South Africa, life expectancy increased considerably after the government introduced its antiretroviral therapy (ART) program in 2004. The impact of the national ART program on life expectancy may be underestimated if child mortality is not accounted fo

Distribution of antiretroviral therapy through private pharmacies and postal courier services during COVID-19 in Botswana: acceptability and reach of two out-of-facility individual differentiated service delivery models.

IntroductionThe advent of COVID‐19 has put pressure on health systems as they implement measures to reduce the risk of transmission to people living with HIV (PLHIV) and healthcare workers. For two out‐of‐facility individual differentiated service delivery (DSD) models, we assessed acceptability of antiretroviral therapy (ART) distribution through private pharmacies and reach of home delivery of ART through courier services during the COVID‐19 pandemic in Botswana.MethodsFrom 24 July to 24 August 2020, we conducted exit interviews with PLHIV receiving ART from 10 high‐volume public facilities in Gaborone, and mapped and conducted an online survey with private pharmacies to assess willingness and capacity to dispense ART to PLHIV enrolled in the Botswana national ART program. We piloted ART home delivery from September 2020 to January 2021 in Gaborone and Kweneng East districts for PLHIV accessing ART at two Tebelopele Wellness Clinics. We used cascade analysis to measure the enrolment and eventual reach (percentage of those reached amongst those who are eligible) of ART home delivery.ResultsSixty‐one PLHIV and 42 private pharmacies participated. Of the PLHIV interviewed, 37 (61%) indicated willingness to access ART from private pharmacies and pay BWP50 (∼US$4) per refill for a maximum of two refills per year. All private pharmacies surveyed were willing to provide ART, and 26 (62%) would charge a dispensing fee (range = BWP50–100; ∼US$4–8) per refill. All pharmacies operated 12 h/day, 6 days/week and on public holidays. In the home delivery pilot, 650 PLHIV were due for refills, 69.5% (n = 452) of whom were eligible for home delivery. Of these, 361 were successfully offered home delivery and 303 enrolled (enrolment = 83.9%: female = 87.2%, male = 77.8%, p = 0.013). A total of 276 deliveries were made, a reach of 61%.ConclusionsProviding ART through private pharmacies and home delivery was acceptable in Botswana during COVID‐19. Surveyed pharmacies were willing and able to dispense ART to PLHIV attending public sector facilities for free or for a nominal fee. Additionally, using courier services for ART home delivery is a novel and viable model in countries with a reliable courier service like Botswana and should be scaled up, particularly in urban areas.

Linkage to care after HIV diagnosis among men who have sex with men and transgender women in Lima, Peru

ABSTRACT In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage within 90 days of HIV diagnosis by matching data from two studies conducted in Lima between 2013 and 2015 to national ART program records. We used generalized linear modeling to assess predictors of timely linkage and late presentation to care. Of 487 newly-diagnosed MSM and TW, only 44% presented for care at an HIV clinic within 90 days. Timely linkage was less common among TW (aPR 0.7, 95% CI 0.5–1.0), those younger than 24 (aPR 0.8, 95% CI 0.6–1.0), and those reporting a history of sex work (aPR 0.7, 95% CI 0.6–0.9). Proximity to an ART program clinic was not associated with linkage; most participants linked to clinics offering “LGBTQ-friendly” care. The pattern of clinics selected by participants suggests the importance of concerns about confidentiality and stigma in decision-making about where to link to care.

Drivers of HIV-1 Drug Resistance to Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTIs) in Nine African Countries: A Modelling Study

Background: The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy (ART) programmes' long-term success. NNRTIs will likely remain an essential drug for the management of HIV-1 due to the adverse effects and safety concerns associated with integrase inhibitors. Mathematical models can contribute to a better understanding of the mechanisms that shape the HIV-1 epidemic and the rise of NNRTI pretreatment resistance in a country. We fitted a dynamic transmission model to data 2000-2018 from nine countries of southern Africa. Methods: We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on NNRTI pretreatment drug resistance from Botswana, Eswatini, Lesotho, Malawi, Mozambique, Namibia, South Africa, Zambia, and Zimbabwe, from a systematic review, UNAIDS and the World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking the country-specific data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined the vulnerability of national ART programmes to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between national ART programme's fragility and the characteristics of health systems and countries. Findings: The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval [CrI] 1.9 to 7.1%) in Mozambique and 25.3% (17.9 to 33.8%) in Eswatini. The proportion of NNRTI pretreatment drug resistance attributable to unregulated antiretroviral use ranged from 6% (95%CrI 2-14) in Eswatini to 64% (95%CrI 26-85) in Mozambique. The fragility index was low in Botswana (0.01; 95%CrI 0.0-0.11) but high in Namibia (0.48; 95% CrI 0.16-10.17), Eswatini (0.64; 95%CrI 0.23-11.8) and South Africa to 1.21 (95%CrI 0.83-9.84). The combination of high fragility of ART programmes and high levels of ART coverage was associated with a sharp increase in NNRTI pretreatment drug resistance. Interpretation: This comparison of nine countries shows that NNRTI pretreatment drug resistance can be controlled despite high ART coverage levels, as in Botswana, Mozambique, or Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART. Funding Statement: National Institute of Allergy and Infectious Diseases (grant 5U01-AI069924-05) and Swiss National Science Foundation (grant 174281). Declaration of Interests: We declare no conflict of interest.

The South African National HIV Pregnancy Cohort: evaluating continuity of care among women living with HIV

BackgroundSouth Africa is home to more people living with HIV than any other country, including nearly one in three pregnant women attending antenatal care. Access to antiretroviral therapy (ART) has increased substantially since the start of the national ART program in 2004, with > 95% ART coverage during pregnancy and delivery, and vertical transmission of HIV greatly reduced. However, women who initiate ART during pregnancy are at heightened risk of dropping out of care, particularly after delivery, leading to the potential for viral transmission, morbidity and mortality. It is difficult to evaluate the success of policies of expanded access to ART care, and assess continuity of care, due to the lack of a national longitudinal HIV care database. Also, patient movement between unlinked facilities. For the first time on a national level, we propose to utilize routinely-collected laboratory data to develop and validate a cohort of pregnant women living with HIV in South Africa in a way that is uniquely robust to facility transfer.MethodsUsing laboratory test data matched to facility type, we will identify entry to antenatal care to build the cohort, then describe key treatment milestones, including 1) engagement in antenatal care, 2) initiation of ART, 3) HIV viremia, and 4) continuity of HIV care in the postpartum period. Second, we will measure the effect of system-wide factors impacting continuity of care among pregnant women. We will assess policies of expanded treatment access on continuity of care using regression-discontinuity analyses. We then will assess mobility and its effect on continuity of care during and after pregnancy. Third, we will identify individual-level risk factors for loss from HIV care in order to develop targeted interventions to improve engagement in HIV care.DiscussionThis work will create the world’s largest national cohort of pregnant women living with HIV. This novel cohort will be a powerful tool available to policymakers, clinicians and researchers for improving our understanding of engagement in care among pregnant women in South Africa and assessing the performance of the South African national ART program in caring for pregnant women living with HIV.Trial registrationN/A (not a clinical trial).

CERVICAL SMEAR ABNORMALITIES IN HIV INFECTED WOMEN ATTENDING A RURAL HOSPITAL ART CENTER IN TAMILNADU

INTRODUCTION: Cervical cancers are the most common form of cancer encountered in Indian women. Studies from India had reported HIV positive women are 10-11 times more prone for cervical carcinomas than HIV negative women with a recent rise in incidence observed. India started a free antiretroviral therapy (ART) program in 2004 with services extended to rural General Hospitals. Cancer cervix can be diagnosed at a preinvasive stage with repeatative papanicolaou smear (cytological screening) and can be readily preventable. AIM: Our aim is to determine the prevalence of PAP smear abnormalities among HIV infected women from rural areas coming for ART initiation and the relationship between immunological status and smear abnormalities. METHODS: As per the Indian National ART program all HIV positive women of reproductive age should undergo PAP smear examination before initiation of ART. All consenting women >18 years of age with history of penetrative vaginal intercourse undergo PAP smear examination. In this observational cohort from 25th June 2011 to 15th January 2012 conducted in Melur ART centre and the cytological reports and the patient clinical and immunological status data was analyzed by using SPSS 17 version. RESULTS: 102 PAP smears were obtained and classified according to Bethesda classification. Five patients (4.90%) were abnormal. Squamous cell carcinoma was observed in 1 (0.98%) patient with a CD4 count of 580 cells/mm3. High squamous intraepithelial lesions were observed in 2 patients (1.96%) with CD4 counts of 208 & 633 cells/mm3 respectively. Low squamous intraepithelial lesion were observed in 2 patients (1.96%) with CD4 counts of 50 and 385 respectively cells/mm3. Immunological status (CD4 count) correlated with grade of the initial lesion (p=0.10). All the patients with PAP smear abnormalities were referred to Madurai Medical College Hospital for further treatment and follow-up. CONCLUSION: In our observational study increasing cytological abnormalities in the HIV Infected women were noted. Accordingly, all ART centre and HIV treatment programs should institute comprehensive reproductive health care services for this high-risk groups, including routine Papanicolaou smear screening

Efficacy and safety of a single-tablet regimen containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and efavirenz 400 mg as a switch strategy in virologically suppressed HIV-1-infected subjects on nonnucleoside reverse transcriptase inhibitor-containing first-line antiretroviral therapy in Pune, India.

ObjectivesAs per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first‐line antiretroviral therapy (ART). This study explored the use of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first‐line switch strategy in PWH in Pune, India.MethodsThis retrospective cohort study was conducted in private sector ART clinics in three tertiary‐level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first‐line ART (predominantly TLE600 STR), completed ≥ 6 months of follow‐up and achieved virological suppression [plasma viral load (VL) < 1000 HIV‐1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow‐up were noted. Grade 3/4 adverse events (especially efavirenz‐related neuropsychiatric adverse events) leading to regimen discontinuation were also noted.ResultsOf 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow‐up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively.ConclusionsTLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR.

Population-based monitoring of HIV drug resistance early warning indicators in Uganda: A nationally representative survey following revised WHO recommendations.

IntroductionWith the scale-up of antiretroviral therapy (ART) there is a need to monitor programme performance to maximize ART efficacy and to prevent emergence of HIV drug resistance (HIVDR). In keeping with the elements of the World Health Organisation (WHO) guidance we carried out a nationally representative assessment of early warning indicators (EWI) at 304 randomly selected ART service outlets in Uganda.MethodsRetrospective patient data was extracted for the six EWIs for HIVDR including; on-time antiretroviral (ARV) drug pick-up, patient retention on ART at 12 months, ART dispensing practices, ARV drug stock-outs, viral load suppression (VLS) and viral load (VL) testing completion. Point prevalence for each clinic and national aggregate prevalence with 95% confidence intervals (CI) for all clinics were estimated and facility performances were computed and association between EWIs and programmatic factors assessed using Fisher’s Exact Test.ResultsFacilities meeting the EWI targets: on-time pill pick-up was 9.5%, more facilities in the north met this target (p = 0.040). Retention on ART at 12 months was 24.1%, facilities in Kampala region (p<0.001) and Specialized ART clinics (p = 0.01) performed better in this indicator. Pharmacy stock-outs was 33.6%, with more facilities in Kampala (p<0.001), specialized ART clinics (p<0.001) and private-for-profit (p<0.001) meeting this target. Dispensing practices was met by 100% of the facilities. VLS was met by 49.2% and 50.8% of facilities met VL completion target with facilities in central region performing better (p<0.001). National prevalence for the EWIs was: on-time pill pick-up 63.3% (CI: 58.9–67.8); retention on ART at 12 months 69.9% (CI: 63.8–76.0); dispensing practices 100.0%; VLS 85.2% (CI: 81.8–88.5) and VL completion, 60.7% (CI: 56.9–64.6).ConclusionDispensing practices in all facilities were in line with the national guidelines however, there still remains a challenge to long-term ART programmatic success in monitoring patient response to treatment, and maintaining patients on ART without interruptions arising due to poor patient adherence and as a consequence of ARV supply interruption. It is therefore of high importance that the national ART program ensures intensified follow-up for patients, ensuring uninterrupted supply of ARV drugs and increasing VL monitoring at treatment centres, in order to improve patient outcomes and avert preventable HIVDR

Retention and predictors of attrition among patients who started antiretroviral therapy in Zimbabwe's national antiretroviral therapy programme between 2012 and 2015.

The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow-up evaluation for the 2012-2015 cohorts to assess the implementation and impact of recommendations from this prior evaluation. A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LTFU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model. A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4% (p-value = 0.060), 86.5% (p-value<0.001), 79.2% (p-value<0.001) and 74.4% (p-value<0.001) at 6, 12, 24 and 36 months respectively. LTFU accounted for 98% of attrition. Being an adolescent or a young adult (15-24 years) (vs adult;1.41; 95% CI:1.14-1.74), children (<15years) (vs adults; aHR 0.64; 95% CI:0.46-0.91), receiving care at primary health care facility (vs central and provincial facility; aHR 1.23; 95% CI:1.01-1.49), having initiated ART between 2014-2015 (vs 2012-2013; aHR1.45; 95%CI:1.24-1.69), having WHO Stage IV (vs Stage I-III; aHR2.06; 95%CI:1.51-2.81) and impaired functional status (vs normal status; aHR1.25; 95%CI:1.04-1.49) predicted attrition. The overall retention was higher in comparison to the previous 2007-2010 evaluation. Further studies to understand why attrition was found to be higher at primary health care facilities are warranted. Implementation of strategies for managing patients with advanced HIV disease, differentiated care for adolescents and young adults and tracking of LTFU clients should be prioritised to further improve retention.

High incidence of tuberculosis in the first year of antiretroviral therapy in the Botswana National antiretroviral therapy programme between 2011 and 2015.

Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana. A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program. Multivariable analysis using Cox regression included sex, age, viral load and CD4 T-cell counts. Of 45 729 patients, with a median follow-up of 1.7 years Q1 : Q3, 0.5, 3.1), 1791 patients developed TB over a median of 1.5 years (Q1 : Q3, 0.3, 3.1) of follow-up (incidence rate 1.9 per 100 person-years; 95% CI 1.8-2.0). At baseline, the median CD4 T-cell count was 272 cells/μl (Q1, Q3 146, 403). The risk of TB was greatest within the first year of ART (incidence rate 2.9 per 100 person-years; 95% CI 2.7-3.1) and in patients with CD4 T-cell counts below 50 cells/μl (incidence rate 8.3/100 person-years; 95% CI 7.1-9.7). Patients with viral loads above 10 000 copies/ml at 3 months post-ART initiation had two times higher risk of TB, hazard ratio 2.5 (95% CI 1.8-2.3). We report a high incidence of TB within the first year of ART and in patients with advanced immunodeficiency. Improved screening strategies and virologic monitoring during this early period on ART, coupled with TB preventive treatment, will reduce the burden of TB.

Interventions to improve the HIV continuum of care in China.

To describe HIV epidemic and interventions for improving HIV continuum of care in China. The reported HIV epidemic has been continuously increasing, partially due to the expansion of active HIV testing campaign. Public health intervention programs have been effective in containing HIV spread among former plasma donors and people who inject drugs (PWID), but more infections occur among heterosexual men and women and young men who have sex with men. Of 1.25 million Chinese people are living with HIV, one-third do not know their status. About two-thirds of diagnosed individuals have used antiretroviral therapy (ART) and two-thirds of those on ART have achieved viral suppression, but some risk groups such as PWID have lower rates. The national free ART program has reduced adult and pediatric mortality and reduced heterosexual transmission. China faces great challenges to reduce HIV sexual transmission, improve the HIV continuum of care, and close the gaps to the UNAIDS Three "90" Targets.

Virologic and immunologic responses of patients on highly active antiretroviral therapy in a rural community health centre in Limpopo, South Africa: A retrospective study.

BackgroundSouth Africa has a high HIV burden. Despite increased uptake of persons living with HIV into the South African national antiretroviral therapy programme, the incidence of HIV increased between 2013 and 2016. Studies suggest that increased community viral suppression results in reduced HIV incidence in that community ‘independent of unsafe sexual behaviours and sharing used syringes’.ObjectiveThe aim of this study was to investigate the viral and immunologic responses of patients, in a rural community health centre in South Africa, to combination antiretroviral therapy (cART) between January 2004 and July 2016.MethodsThis was a retrospective medical record review conducted in Thohoyandou Community Health Centre. Data analysis was done using SPSS 24.0 and Microsoft Excel. The estimates used were 95% confidence intervals, and a p-value < 0.05 was considered to be statistically significant.ResultsAnalysis was done using 1247 individuals, with 76% of the cohort being female and 98% first-line cART. The proportion of patients with a suppressed viral load (VL) at 6 months post-treatment was 64%, and 72% at 60 months. Fifty-nine per cent had consistent viral suppression over a 6-month period and 14% over at least 54 months. The mean CD4+ cell count at baseline was 227 cells/µL, and 538 cells/µL at 60 months. Multivariate regression analysis revealed that males had poorer immunologic and virologic responses.ConclusionsViral suppression in the study population was inferior to the UNAIDS target of 90%. The sustainability of viral suppression, once attained, was also low. These may have a negative impact on HIV transmission.

Virologic and immunologic responses of patients on highly active antiretroviral therapy in a rural community health centre in Limpopo, South Africa: A retrospective study

Background: South Africa has a high HIV burden. Despite increased uptake of persons living with HIV into the South African national antiretroviral therapy programme, the incidence of HIV increased between 2013 and 2016. Studies suggest that increased community viral suppression results in reduced HIV incidence in that community ‘independent of unsafe sexual behaviours and sharing used syringes’. Objective: The aim of this study was to investigate the viral and immunologic responses of patients, in a rural community health centre in South Africa, to combination antiretroviral therapy (cART) between January 2004 and July 2016. Methods: This was a retrospective medical record review conducted in Thohoyandou Community Health Centre. Data analysis was done using SPSS 24.0 and Microsoft Excel. The estimates used were 95% confidence intervals, and a p -value &lt; 0.05 was considered to be statistically significant. Results: Analysis was done using 1247 individuals, with 76% of the cohort being female and 98% first-line cART. The proportion of patients with a suppressed viral load (VL) at 6 months post-treatment was 64%, and 72% at 60 months. Fifty-nine per cent had consistent viral suppression over a 6-month period and 14% over at least 54 months. The mean CD4+ cell count at baseline was 227 cells/µL, and 538 cells/µL at 60 months. Multivariate regression analysis revealed that males had poorer immunologic and virologic responses. Conclusions: Viral suppression in the study population was inferior to the UNAIDS target of 90%. The sustainability of viral suppression, once attained, was also low. These may have a negative impact on HIV transmission.

Pretreatment HIV Drug Resistance and Virologic Outcomes to First-Line Antiretroviral Therapy in Peru.

Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pre-ART HIV drug resistance (PDR) among antiretroviral (ARV)-naive Peruvians. Given that PDR has been associated with virologic failure (VF) of ART, in 2014-2015 we enrolled a follow-up cohort at the same institution to determine whether the rate of transmitted resistance had increased and compared virologic outcomes of those with and without PDR. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). Rates of VF (plasma HIV RNA >200 copies/mL) were compared between those with and without PDR. Among 122 ARV-naive adults, PDR was detected by OLA in 17 (13.9%) adults. Compared with the 2007-2009 cohort, the proportion with PDR at OLA codons was significantly increased (p < .001). A total of 11 of 19 OLA mutations conferring high-level drug resistance were also detected by CS, and 8 additional participants had mutations encoding low-level resistance detected by CS for a total of 25 participants (20.5%). VF at month 6 of NNRTI-ART appeared greater in participants with versus without PDR [4/18 (22.2%) vs. 3/71 (4.2%); p = .03]. An increasing prevalence of PDR was detected among ARV-naive Peruvians. Studies are needed to determine risks of specific PDR mutations.

Implementing an Integrated Pharmaceutical Management Information System for Antiretrovirals and Other Medicines: Lessons From Namibia.

The success of the Namibian government's "treatment for all" approach to control and stop the country's HIV epidemic is dependent on an uninterrupted supply of antiretrovirals (ARVs) for people living with HIV. The public health system in Namibia, however, was constrained by an inefficient paper-based pharmaceutical information system resulting in unreliable and inaccessible data, contributing to persistent stock-outs of ARVs and other essential pharmaceuticals. This article describes the incremental implementation of an integrated pharmaceutical management information system to provide timely and reliable commodity and patient data for decision making in Namibia's national antiretroviral therapy (ART) program and the Ministry of Health and Social Services (MoHSS). The system has 4 interlinked information tools: (1) the Electronic Dispensing Tool (EDT) that manages the dispensing and inventory of antiretrovirals at service delivery points; (2) the EDT national database, which facilitates the flow, storage, and collation of ART data at the central level; (3) the Facility Electronic Stock Card used to manage pharmaceutical stocks and report inventory movement data to the national level; and (4) the Pharmaceutical Management Information Dashboard that integrates all 3 tools plus the warehouse management tool used by the central and regional medical stores into 1 dashboard that serves as a platform for the analysis and dissemination of pharmaceutical information throughout the health system. Implementing the pharmaceutical management information system was a prolonged and complicated process, with key challenges related to user acceptance and human resource constraints. The integrated pharmaceutical management information system enables Namibia to collect more than 90% of transactional commodity and patient dispensing data from more than 85% of all ART sites. Health managers use information from the system for medicine quantification decisions and to improve pharmaceutical service delivery. The MoHSS and its partners in the national ART program use the information for monitoring the World Health Organization early warning indicators for HIV drug resistance; ART defaulter tracing; and for planning, reporting, and research purposes. Namibia's pharmaceutical management information system demonstrates the feasibility and benefits of integrating related tools while maintaining their specialized functionality to address country-specific information and inventory management needs.

Third-Line Antiretroviral Therapy Program in the South African Public Sector: Cohort Description and Virological Outcomes.

Background:The World Health Organization recommends that antiretroviral therapy (ART) programs in resource-limited settings develop third-line ART policies. South Africa developed a national third-line ART program for patients who have failed both first-line non-nucleoside reverse transcriptase inhibitor–based ART and second-line protease inhibitor (PI)-based ART. We report on this program.Methods:Third-line ART in South Africa is accessed through a national committee that assesses eligibility and makes individual regimen recommendations. Criteria for third-line include the following: ≥1 year on PI-based ART with virologic failure, despite adherence optimization, and genotypic antiretroviral resistance test showing PI resistance. We describe baseline characteristics and resistance patterns of this cohort and present longitudinal data on virological suppression rates.Results:Between August 2013 and July 2014, 144 patients were approved for third-line ART. Median age was 41 years [interquartile range (IQR): 19–47]; 60% were women (N = 85). Median CD4+ count and viral load were 172 (IQR: 128–351) and 14,759 (IQR: 314–90,378), respectively. About 2.8% started PI-based ART before 2004; 11.1% from 2004 to 2007; 31.3% from 2008 to 2011; and 6.3% from 2012 to 2014 (48.6% unknown start date). Of the 144 patients, 97% and 98% had resistance to lopinavir and atazanavir, respectively; 57% had resistance to darunavir. All were initiated on a regimen containing darunavir, with raltegravir in 101, and etravirine in 33. Among those with at least 1 viral load at least 6 months after third-line approval (n = 118), a large proportion (83%, n = 98) suppressed to <1000 copies per milliliter, and 79% (n = 93) to <400 copies per milliliter.Conclusion:A high proportion of third-line patients with follow-up viral loads are virologically suppressed.

Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program

BackgroundFor patients on antiretroviral therapy (ART), treatment interruptions can impact patient outcomes and result in the accumulation of drug resistance mutations leading to virologic failure. There are minimal published data on the impact of an ART stock shortage on development of drug resistance mutations (DRMs). In this report, we evaluate data from patients enrolled in the Government of Nigeria National ART Program that were receiving treatment at the time of a national drug shortage in late 2003.MethodsWe conducted a cross-sectional evaluation of samples collected between December 2004 and August 2005 from ART patients in virologic failure that either had a treatment interruption or did not during the late 2003 drug shortage period at the Jos University Teaching Hospital (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and mutation profiles were categorized to evaluate predicted drug susceptibility. Data were analyzed to examine factors associated with development of resistance mutations. A genotypic sensitivity score to the alternate recommended regimen was computed to assess drug susceptibility if regimens were changed.ResultsA total of 56 patients were included in this evaluation (28 interrupted, 28 uninterrupted). Patients in the interrupted group had more DRMs than those in the uninterrupted group (p < 0.001); interrupted patients were more likely than uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs. 21.3% uninterrupted; p = 0.04). There was a statistically significant difference in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011) and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug interruption status. Examining genotypic sensitivity scores, we found that 67.9% of the interrupted patients, as compared to 25.0% of the uninterrupted patients, did not have full susceptibility to one drug in the regimen to which guidelines recommended they be switched (p = 0.001).DiscussionIn this small observational study, we found evidence of a difference in resistance profiles and ART susceptibility between those that were stocked-out of drug versus those that were not. We believe that these data are relevant for many other low- and middle-income countries (LMIC) that also experienced similar ART shortages as they rapidly scaled up their national programs.

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi

BackgroundMalawi’s national antiretroviral therapy program provides atazanavir/ritonavir–based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi.MethodsWe conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model.ResultsOut of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25–40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure.ConclusionsAmong patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting.