Adult Antiretroviral Therapy Research Articles

Assessment of adherence and factors contributing to non-adherence among patients on anti-retroviral therapy in a tertiary care hospital: A cross sectional study.

Background:For the successful treatment of human immunodeficiency virus (HIV), it is important that drugs should be taken regularly. Non-adherence not only increases chances of failure of treatment but also leads to the development of resistance to drugs and hence more focus has been given to adherence in the treatment protocol of HIV.Objectives:To determine the level of adherence, its determinants, and to ascertain reasons for non-adherence of antiretroviral therapy (ART) in patients with HIV/acquired immunodeficiency syndrome (AIDS).Methods:A cross-sectional study conducted at an adult ART clinic over a period of one year. The sample size was 320. A systematic random sampling technique was used. Semi-structured Adult AIDS Clinical Trials Group questionnaire was used. Beck Depression Inventory (BDI-II) for current depression and self-report of four days recall method and multi-method approach were used for adherence measurement.Results:The mean age of respondents was 37.26 ± 8.3 years. About 60.3% were males, 34.1% females, and 5.6% were transgenders (TGs). High adherence was found in 87.2% by self-report and 72.5% by multi-method approach. History of opportunistic infection and depression were found to be the best predictors of adherence. Reasons for short term non-adherence were found to be simply forgot to take medications, being away from home, busy with other things, and ran out of pills. Reasons for long-term non-adherence were financial difficulty, side-effects, and shift to alternate therapy.Conclusions:Significant non-adherence to ART necessitates addressing adherence issues in pre-ART counseling, the involvement of family and social support.

Lessons for test and treat in an antiretroviral programme after decentralisation in Uganda: a retrospective analysis of outcomes in public healthcare facilities within the Lablite project.

We describe the decentralisation of antiretroviral therapy (ART) alongside Option B+ roll-out in public healthcare facilities in the Lablite project in Uganda. Lessons learned will inform programmes now implementing universal test and treat (UTT). Routine data were retrospectively extracted from ART registers between October 2012 and March 2015 for all adults and children initiating ART at two primary care facilities (spokes) and their corresponding district hospitals (hubs) in northern and central Uganda. We describe ART initiation over time and retention and use of Cox models to explore risk factors for attrition due to mortality and loss to follow-up. Results from tracing of patients lost to follow-up were used to correct retention estimates. Of 2100 ART initiations, 1125 were in the north, including 944 (84%) at the hub and 181 (16%) at the spokes; children comprised 95 (10%) initiations at the hubs and 14 (8%) at the spokes. Corresponding numbers were 642 (66%) at the hub and 333 (34%) at the spokes in the central region (77 [12%] and 22 [7%], respectively, in children). Children <3y of age comprised the minority of initiations in children at all sites. Twenty-three percent of adult ART initiations at the north hub were Option B+ compared with 45% at the spokes (25% and 65%, respectively, in the central region). Proportions retained in care in the north hub at 6 and 12mo were 92% (95% CI 90 to 93) and 89% (895% CI 7 to 91), respectively. Corresponding corrected estimates in the north spokes were 87% (95% CI 78 to 93) and 82% (95% CI 72 to 89), respectively. In the central hub, corrected estimates were 84% (95% CI 80 to 87) and 78% (95% CI 74 to 82), and were 89% (95% CI 77.9 to 95.1) and 83% (95% CI 64.1 to 92.9) at the spokes, respectively. Among adults newly initiating ART, being older was independently associated with a lower risk of attrition (adjusted hazard ratio [aHR] 0.93 per 5y [95% CI 0.88 to 0.97]). Other independent risk factors included initiating with a tenofovir-based regimen vs zidovudine (aHR 0.60 [95% CI 0.46 to 0.77]), year of ART initiation (2013 aHR 1.55 [95% CI 1.21 to 1.97], ≥2014 aHR 1.41 [95% CI 1.06 to 1.87]) vs 2012, hub vs spoke (aHR 0.35 [95% CI 0.29 to 0.43]) and central vs north (aHR 2.28 [95% CI 1.86 to 2.81]). Independently, patient type was associated with retention. After ART decentralisation, people living with human immunodeficiency virus (HIV) were willing to initiate ART in rural primary care facilities. Retention on ART was variable across facilities and attrition was higher among some groups, including younger adults and women initiating ART during pregnancy/breastfeeding. Interventions to support these groups are required to optimise benefits of expanded access to HIV services under UTT.

The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America.

Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these conditions on mortality in the region. We included adults enrolled during 2001-2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4of <200 cells/μL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.

Evaluation of treatment response, drug resistance and HIV-1 variability among adolescents on first- and second-line antiretroviral therapy: a study protocol for a prospective observational study in the centre region of Cameroon (EDCTP READY-study)

BackgroundSub-Saharan Africa (SSA) alone has nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million), with the potentials to reach adulthood. However, despite an overall reduction in HIV-related mortality, there are increasing deaths among adolescents living with HIV (ADLHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response and longer life expectancy. Interestingly, with uptakes in prevention of mother-to-child transmission, challenges in ART programs, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent ART options for SSA ADLHIV.ObjectivesAmong Cameroonian ADLHIV receiving ART, we shall evaluate the rate of immunovirologic failure, acquired HIVDR-associated mutations, HIV-1 subtype distribution, genetic variability in circulating (plasma) versus archived (cellular) viral strains, and HIVDR early warning indicators (EWIs) at different time-points.MethodsA prospective and observational study will be conducted among 250 ADLHIV (10–19 years old) receiving ART in the centre region of Cameroon, and followed-up at 6 and 12 months after enrollment. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia > = 1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12 months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired-HIVDR, and mortality.DiscussionOur findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ADLHIV within SSA.

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis.

Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB. This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation. Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion. Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.

Effects of adult health interventions at scale on children’s schooling: Evidence from antiretroviral therapy in Zambia

In 2007, approximately one in five children in Zambia lived with an HIV positive adult. We identify the effect of adult antiretroviral therapy (ART) availability at scale on children’s educational outcomes by combining data on the expansion of ART availability with two national household surveys that include HIV testing. Through a triple difference specification, we find that the availability of ART increased the likelihood that children in households with HIV positive household heads started school on time and were the appropriate grade-for-age. Two mechanisms were likely decreased incidental infections in the household and related care giving duties.

Paediatric Integrase Inhibitor Use in a Real-Life Setting: A Single-Centre Cohort Experience 2009-2018.

Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation. We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre. Fifty-six INSTI-based regimens were prescribed in 54 children, 64.9% from 2015 onwards. Twenty-one of 56 (37.5%) regimens commenced with raltegravir, 29 (51.8%) with dolutegravir and six (10.7%) with elvitegravir. The median age at the start of treatment was 15years (interquartile range 13.5-16.4) with a median duration of INSTI-antiretroviral therapy of 1.65years (range 0.01-8.8). Twenty-four children had a detectable viral load at the start INSTI therapy; 20 (83%) achieving viral suppression in a median of 26days (interquartile range 19.5-34.5). There were 26 discontinuations of INSTI-based antiretroviral therapy after a median of 183days; 9/26 because of adverse events. Four of nine adverse events were attributed to INSTI use, all in patients taking dolutegravir and the adverse events were neuropsychiatric and gastrointestinal in nature. INSTI-based regimens were generally efficacious and well tolerated in this paediatric cohort, with 4/26 discontinuations due to INSTI-attributed adverse events. Further post-marketing surveillance of INSTI use in children is warranted.

Late Onset of Antiretroviral Therapy in Adults Living with HIV in an Urban Area in Brazil: Prevalence and Risk Factors.

Introduction Highly active antiretroviral therapy has been available since 1996. Early initiation of antiretroviral therapy (ART) leads to improved therapeutic response and reduced HIV transmission. However, a significant number of people living with HIV (PLHIV) still start treatment late. Objective This study aimed to analyze characteristics and factors associated with late initiation of ART among HIV-infected treatment-naïve patients. Methods This cross-sectional study included PLHIV older than 17 years who initiated ART at two public health facilities from 2009 to 2012, in a city located in Midwestern Brazil. Pregnant women were excluded. Data were collected from medical records, antiviral dispensing forms, and the Logistics Control of Medications System (SICLOM) of the Brazilian Ministry of Health. Late initiation of ART was defined as CD4+ cell count < 200 cells/mm3 or presence of AIDS-defining illness. Uni- and multivariate analysis were performed to evaluate associated factors for late ARV using SPSS®, version 21. The significance level was set at p<0.05. Results 1,141 individuals were included, with a median age of 41 years, and 69.1% were male. The prevalence of late initiation of ART was 55.8% (95%CI: 52.9-58.7). The more common opportunistic infections at ART initiation were pneumocystosis, cerebral toxoplasmosis, tuberculosis, and histoplasmosis. Overall, 38.8% of patients had HIV viral load equal to or greater than 100,000 copies/mL. Late onset of ART was associated with higher mortality. After logistic regression, factors shown to be associated with late initiation of ARV were low education level, sexual orientation, high baseline viral load, place of residence outside metropolitan area, and concomitant infection with hepatitis B virus. Conclusion These results revealed the need to increase early treatment of HIV infection, focusing especially on groups of people who are more socially vulnerable or have lower self-perceived risk.

Success and failure of initial antiretroviral therapy in adults: an updated systematic review.

We updated a prior systematic review of initial antiretroviral therapy (ART) efficacy through week 144. Studies (1994 to July 2017) were drawn from PubMed, ClinicalTrials.gov, Cochrane Library, and major conferences; design, eligibility, patient, and ART data were abstracted. Outcomes are expressed as group size-weighted means. Mixed-effects meta-regression was used to identify sources of efficacy heterogeneity. Within 354 groups (181 studies, 77 999 participants), principal backbones were tenofovir-emtricitabine (TDF/TAF-FTC) (44.2%), thymidine-based (27.7%), and abacavir-lamivudine (9.7%). Principal anchors were non-nucleoside analog (49.7%), boosted protease inhibitor (28.1%), and integrase inhibitor (INSTI; 11.5%). Mean intention-to-treat efficacy (RNA <50 copies/ml) was 71.3%, 63.5% (145 groups), and 61.8% (48 groups) at weeks 48, 96, and 144, respectively (for post-2010 studies, 83.8%, 79.9%, and 77.1%). TDF/TAF-FTC and INSTI were independent predictors of greater efficacy at weeks 48, 96, and 144. Additional independent predictors at week 48 were pre-ART resistance genotyping, higher baseline CD4 cell count, and once-daily ART. Fewer pills per day predicted greater efficacy at weeks 96 and 144. Phase 4 studies yielded progressively inferior efficacy than phase 3 studies (difference 5.1% at week 48, 15.8% at week 144). Cessation through week 144 overall (29.4%) and for adverse events (8.9%) declined over time, but cessation for virological failure (5.2%) did not. Initial ART efficacy continues to improve, but more than 20% of post-2010 patients failed over 3 years. Real-world efficacy is lower than in phase 3 trials. Guidelines should list non-INSTI-based initial ART as nonpreferred. Strategies are needed to improve access to pre-ART genotyping and to increase early initiation of once-daily ART.

Effects of short-term cash and food incentives on food insecurity and nutrition among HIV-infected adults in Tanzania.

Food insecurity impedes antiretroviral therapy (ART) adherence. We previously demonstrated that short-term cash and food incentives increased ART possession and retention in HIV services in Tanzania. To elucidate potential pathways that led to these achievements, we examined whether incentives also improved food insecurity. Three-arm randomized controlled trial. From 2013 to 2015, 805 food-insecure adult ART initiates (≤90 days) at three clinics were randomized to receive cash or food transfers (∼$11 per month for ≤6 months, conditional on visit attendance) or standard-of-care (SOC) services. We assessed changes from baseline to 6 and 12 months in: food insecurity (severe; access; dietary diversity), nutritional status (body weight; BMI), and work status. Difference-in-differences average treatment effects were estimated using inverse-probability-of-censoring-weighted longitudinal regression models. The modified intention-to-treat analysis included 777 nonpregnant participants with 41.6% severe food insecurity. All three study groups experienced improvements from baseline in food insecurity, nutritional status, and work status. After 6 months, severe food insecurity declined within the cash (-31.4% points to 11.5%) and food (-30.3 to 10.4%) groups, but not within the SOC. Relative to the SOC, severe food insecurity decreased by an additional 24.3% points for cash (95% CI -45.0 to -3.5) and 23.3% percent points for food (95% CI -43.8 to -2.7). Neither intervention augmented improvements in severe food insecurity at 12 months, nor food access, dietary diversity, nutritional status, or work status at 6 or 12 months. Small cash and food transfers provided at treatment initiation may mitigate severe food insecurity. These effects may have facilitated previously observed improvements in ART adherence.

Community delivery of antiretroviral drugs: A non-inferiority cluster-randomized pragmatic trial in Dar es Salaam, Tanzania.

BackgroundWith the increase in people living with HIV in sub-Saharan Africa and expanding eligibility criteria for antiretroviral therapy (ART), there is intense interest in the use of novel delivery models that allow understaffed health systems to successfully deal with an increasing demand for antiretroviral drugs (ARVs). This pragmatic randomized controlled trial in Dar es Salaam, Tanzania, evaluated a novel model of ARV community delivery: lay health workers (home-based carers [HBCs]) deliver ARVs to the homes of patients who are clinically stable on ART, while nurses and physicians deliver standard facility-based care for patients who are clinically unstable. Specifically, the trial aimed to assess whether the ARV community delivery model performed at least equally well in averting virological failure as the standard of care (facility-based care for all ART patients).Methods and findingsThe study took place from March 1, 2016, to October 27, 2017. All (48) healthcare facilities in Dar es Salaam that provided ART and had an affiliated team of public-sector HBCs were randomized 1:1 to either (i) ARV community delivery (intervention) or (ii) the standard of care (control). Our prespecified primary endpoint was the proportion of adult non-pregnant ART patients with virological failure at the end of the study period. The prespecified margin of non-inferiority was a risk ratio (RR) of 1.45. The mean follow-up period was 326 days. We obtained intent-to-treat (ITT) RRs using a log-binomial model adjusting standard errors for clustering at the level of the healthcare facility. A total of 2,172 patients were enrolled at intervention (1,163 patients) and control (1,009 patients) facilities. Of the 1,163 patients in the intervention arm, 516 (44.4%) were both clinically stable on ART and opted to receive ARVs in their homes or at another meeting point of their choosing in the community. At the end of the study period, 10.9% (95/872) of patients in the control arm and 9.7% (91/943) in the intervention arm were failing virologically. The ITT RR for virological failure demonstrated non-inferiority of the ARV community delivery model (RR 0.89 [1-sided 95% CI 0.00–1.18]). We observed no significant difference between study arms in self-reported patient healthcare expenditures over the last 6 months before study exit. Of those who received ARVs in the community, 97.2% (95% CI 94.7%–98.7%) reported being either “satisfied” or “very satisfied” with the program. Other than loss to follow-up (18.9% in the intervention and 13.6% in the control arm), the main limitation of this trial was that substantial decongestion of healthcare facilities was not achieved, thus making the logic for our preregistered ITT approach (which includes those ineligible to receive ARVs at home in the intervention sample) less compelling.ConclusionsIn this study, an ARV community delivery model performed at least as well as the standard of care regarding the critical health indicator of virological failure. The intervention did not significantly reduce patient healthcare expenditures, but satisfaction with the program was high and it is likely to save patients time. Policy-makers should consider piloting, evaluating, and scaling more ambitious ARV community delivery programs that can reach higher proportions of ART patients.Trial registrationClinicalTrials.gov NCT02711293.

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings.

IntroductionSurveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naïve populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART.MethodsEDTA-venous blood was collected to prepare DBS from adult and pediatric ART patients receiving treatment during the previous 12–36 months. DBS were stored at ambient temperature for two weeks and then at -80°C until shipment at ambient temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta. Viral load (VL) was determined using NucliSENS EasyQ® HIV-1 v2.0 kits; HIVDR genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits.ResultsDBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these specimens had VL ≥1,000 copies/mL in Kenya and Tanzania, respectively. The overall genotyping rate of those DBS with VL ≥1,000 copies/mL was 93.0% (95% CI: 89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times for the HIVDR surveys from the time of collecting DBS to completing laboratory testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys, respectively.ConclusionsThe study demonstrates a favorable outcome of using DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm that DBS collected and stored at ambient temperature for two weeks, and shipped with routine courier services are a reliable sample type for large-scale surveillance of acquired HIVDR.

Peer-Delivered Linkage Case Management and Same-Day ART Initiation for Men and Young Persons with HIV Infection - Eswatini, 2015-2017.

To achieve epidemic control of human immunodeficiency virus (HIV) infection, sub-Saharan African countries are striving to diagnose 90% of HIV infections, initiate and retain 90% of HIV-diagnosed persons on antiretroviral therapy (ART), and achieve viral load suppression* for 90% of ART recipients (90-90-90) (1). In Eswatini (formerly Swaziland), the country with the world's highest estimated HIV prevalence (27.2%), achieving 90-90-90 depends upon improving access to early ART for men and young adults with HIV infection, two groups with low ART coverage (1-3). Although community-based strategies test many men and young adults with HIV infection in Eswatini, fewer than one third of all persons who test positive in community settings enroll in HIV care within 6 months of diagnosis after receiving standard referral services (4,5). To evaluate the effectiveness of peer-delivered linkage case management† in improving early ART initiation for persons with HIV infection diagnosed in community settings in Eswatini, CDC analyzed data on 651 participants in CommLink, a community-based, mobile HIV-testing, point-of-diagnosis HIV care, and peer-delivered linkage case management demonstration project, and found that after diagnosis, 635 (98%) enrolled in care within a median of 5 days (interquartile range [IQR] = 2-8 days), and 541 (83%) initiated ART within a median of 6 days (IQR = 2-14 days), including 402 (74%) on the day of their first clinic visit (same-day ART). After expanding ART eligibility to all persons with HIV infection on October 1, 2016, 96% of 225 CommLink clients initiated ART, including 87% at their first clinic visit. Compared with women and adult clients aged ≥30 years, similar high proportions of men and persons aged 15-29 years enrolled in HIV care and received same-day ART. To help achieve 90-90-90 by 2020, the United States President's Emergency Plan for AIDS Relief (PEPFAR) is supporting the national scale-up of CommLink in Eswatini and recommending peer-delivered linkage case management as a potential strategy for countries to achieve >90% early enrollment in care and ART initiation after diagnosis of HIV infection (6).

Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana.

Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study, and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study, all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study (n = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's (n = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.

Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial.

BackgroundAs the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa.Methods and findingsWe conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)—immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women’s retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother–infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12–0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes.ConclusionsIn this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV.Trial registrationClinicalTrials.gov NCT01933477.

Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study

SummaryBackgroundThere is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high.MethodsThe HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year.FindingsA transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost.InterpretationA future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance.FundingBill & Melinda Gates Foundation, World Health Organization.

Effectiveness of early initiation of antiretroviral therapy in adults with HIV associated tuberculosis in Lesotho in 2012

Background:Lesotho has a huge burden of human immunodeficiency virus associated tuberculosis (HIV-TB). In this study we compared the effectiveness of early versus late commencement of antiretroviral therapy (ART) in adults living with HIV-TB in Lesotho.Methods: Three out of 17 hospitals were randomly selected and data extracted from the hospitals’ tuberculosis (TB) treatment registers for 247 adults living with HIV-TB who completed TB therapy during the first quarter of 2012.Results: Eighty (32%) commenced ART early (4 weeks), 100 (41%) were started late (≥4 weeks) and 67 (27%) received no ART. Both early and late ART initiators were more likely to have a successful TB outcome (Adjusted Odds Ratio (AOR) 10.1, 95% CI: 3.7 - 27.5 and AOR 8.4, 95% CI: 3.4 - 20.6, respectively) relative to the group who had no ART (p 0.001).Conclusions: Effective treatment exists for managing HIV-TB simultaneously. The guidelines for initiation of ART in adult HIV-TB in Lesotho have not been fully implemented, but those who commenced ART had significant clinical benefits. Health departments must address the challenges encountered in treating HIV-TB simultaneously to ensure those co-infected receive optimal care.

Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.

In human immunodeficiency virus (HIV)-infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults. The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIV-infected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression. A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/μL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26-5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36-2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality. African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population. NCT00495651.

Effectiveness of early initiation of antiretroviral therapy in adults with HIV associated tuberculosis in Lesotho in 2012

Background: Lesotho has a huge burden of human immunodeficiency virus associated tuberculosis (HIV-TB). In this study we compared the effectiveness of early versus late commencement of antiretroviral therapy (ART) in adults living with HIV-TB in Lesotho.Methods: Three out of 17 hospitals were randomly selected and data extracted from the hospitals’ tuberculosis (TB) treatment registers for 247 adults living with HIV-TB who completed TB therapy during the first quarter of 2012.Results: Eighty (32%) commenced ART early (<4 weeks), 100 (41%) were started late (≥4 weeks) and 67 (27%) received no ART. Both early and late ART initiators were more likely to have a successful TB outcome (Adjusted Odds Ratio (AOR) 10.1, 95% CI: 3.7 - 27.5 and AOR 8.4, 95% CI: 3.4 - 20.6, respectively) relative to the group who had no ART (p < 0.001).Conclusions: Effective treatment exists for managing HIV-TB simultaneously. The guidelines for initiation of ART in adult HIV-TB in Lesotho have not been fully implemented, but those w...

Bayesian projection of life expectancy accounting for the HIV/AIDS epidemic.

BackgroundWhile probabilistic projection methods for projecting life expectancy exist, few account for covariates related to life expectancy. Generalized HIV/AIDS epidemics have a large, immediate negative impact on the life expectancy in a country, but this impact can be mitigated by widespread use of antiretroviral therapy (ART). Thus, projection methods for countries with generalized HIV/AIDS epidemics could be improved by accounting for HIV prevalence, the future course of the epidemic, and ART coverage.MethodsWe extend the current Bayesian probabilistic life expectancy projection methods of Raftery et al. (2013) to account for HIV prevalence and adult ART coverage in countries with generalized HIV/AIDS epidemics.ResultsWe evaluate our method using out-of-sample validation. We find that the proposed method performs better than the method that does not account for HIV prevalence or ART coverage for projections of life expectancy in countries with a generalized epidemic, while projections for countries without an epidemic remain essentially unchanged.ConclusionsIn general, our projections show rapid recovery to pre-epidemic life expectancy levels in the presence of widespread ART coverage. After the initial life expectancy recovery, we project a steady rise in life expectancy until the end of the century.ContributionWe develop a simple Bayesian hierarchical model for long-term projections of life expectancy while accounting for HIV/AIDS prevalence and coverage of ART. The method produces well-calibrated projections for countries with generalized HIV/AIDS epidemics up to 2100 while having limited data demands.