Rapid Scale-up Of Antiretroviral Therapy Research Articles

Magnitude and associated factors of virological failure among children on ART in Bahir Dar Town public health facilities, Northwest Ethiopia: a facility based cross-sectional study

BackgroundDespite the rapid scale-up of antiretroviral therapy, virologic failure has become global public health concern and challenge, especially in developing countries. Viral load monitoring is an important approach to identify treatment failure and develop public health interventions in children receiving antiretroviral therapy. Thus, this study aims to assess the magnitude and associated factors of virological failure among children on antiretroviral therapy.MethodsA facility-based cross-sectional study was conducted among 399 HIV-positive children on antiretroviral therapy from 2016 to 2019 in Bahir Dar Town public health facilities. Data were extracted from children’s charts using a standardized data extraction tool, adapted from ART intake and follow-up forms. Data were entered using Epi-Data Version 3.1, and analyzed using SPSS Version 25. Bivariable and multivariable binary logistic regression models were done to identify factors associated with virological failure. Variables with p-values < 0.25 were fitted into the multivariable analysis. Finally, variables with p-values <0.05 were considered as statistically significant factors.ResultsThe period prevalence of virological failure was found to be 14.8% (95% CI: 11.5–19.3%). Opportunistic infections (AOR = 2.19, CI: 1.13–4.25), history of treatment interruption and restart (AOR = 2.21, CI: 1.09–4.54), younger age (AOR = 2.42, CI: 1.02–5.74), poor/fair ART adherence (AOR = 2.19, CI: 1.05–4.57), and advanced baseline WHO clinical staging (AOR = 2.32, CI: 1.14–4.74) were found to be factors significantly associated with virological failure.ConclusionThe magnitude of virological failure among HIV-infected children remained high. Children with poor/fair ART adherence, history of treatment interruption, advanced baseline WHO clinical staging, younger age, and opportunistic infections were significantly associated with virologic failure. Thus, special attention should be given to children who had poor/fair ART adherence and presenting with opportunistic infections.

The effect of 90-90-90 on HIV-1 incidence and mortality in eSwatini: a mathematical modelling study

SummaryBackgroundThe rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030.MethodsWe used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15–49 by 2016, 2030, and 2050.FindingsBetween 2010 and 2016, status-quo ART scale-up among adults (aged 15–49 years) in eSwatini (from 34·0% in 2010 to 74·1% in 2016) reduced HIV incidence by 43·57% (95% credible interval 39·71 to 46·36) and HIV mortality by 56·17% (54·06 to 58·92) among individuals aged 15–49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1·09 (0·87 to 1·29) per 100 person-years, 1·42 (1·13 to 1·71) per 100 person-years among women and 0·79 (0·63 to 0·94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15–24 years (an additional 17·37% [7·33 to 26·12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35–49 years (1·99% [–5·09 to 7·74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection—an upper bound of plausible treatment effect—would reduce adult HIV incidence to 0·73 infections (0·55 to 0·92) per 100 person-years by 2030 and 0·46 (0·33 to 0·59) per 100 person-years by 2050.InterpretationScale-up of ART over the last decade has already contributed to substantial reductions in HIV-1 incidence and mortality in eSwatini. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures.FundingGlobal Good Fund and the Bill & Melinda Gates Foundation.

From Sequence Data to Patient Result: A Solution for HIV Drug Resistance Genotyping With Exatype, End to End Software for Pol-HIV-1 Sanger Based Sequence Analysis and Patient HIV Drug Resistance Result Generation.

Introduction:With the rapid scale-up of antiretroviral therapy (ART) to treat HIV infection, there are ongoing concerns regarding probable emergence and transmission of HIV drug resistance (HIVDR) mutations. This scale-up has to lead to an increased need for routine HIVDR testing to inform the clinical decision on a regimen switch. Although the majority of wet laboratory processes are standardized, slow, labor-intensive data transfer and subjective manual sequence interpretation steps are still required to finalize and release patient results. We thus set out to validate the applicability of a software package to generate HIVDR patient results from raw sequence data independently.Methods:We assessed the performance characteristics of Hyrax Bioscience’s Exatype (a sequence data to patient result, fully automated sequence analysis software, which consolidates RECall, MEGA X and the Stanford HIV database) against the standard method (RECall and Stanford database). Exatype is a web-based HIV Drug resistance bioinformatic pipeline available at sanger.exatype.com. To validate the exatype, we used a test set of 135 remnant HIV viral load samples at the National HIV Reference Laboratory (NHRL).Result:We analyzed, and successfully generated results of 126 sequences out of 135 specimens by both Standard and Exatype software. Result production using Exatype required minimal hands-on time in comparison to the Standard (6 computation-hours using the standard method versus 1.5 Exatype computation-hours). Concordance between the 2 systems was 99.8% for 311,227 bases compared. 99.7% of the 0.2% discordant bases, were attributed to nucleotide mixtures as a result of the sequence editing in Recall. Both methods identified similar (99.1%) critical antiretroviral resistance-associated mutations resulting in a 99.2% concordance of resistance susceptibility interpretations. The Base-calling comparison between the 2 methods had Cohen’s kappa (0.97 to 0.99), implying an almost perfect agreement with minimal base calling variation. On a predefined dataset, RECall editing displayed the highest probability to score mixtures accurately 1 vs. 0.71 and the lowest chance to inaccurately assign mixtures to pure nucleotides (0.002–0.0008). This advantage is attributable to the manual sequence editing in RECall.Conclusion:The reduction in hands-on time needed is a benefit when using the Exatype HIV DR sequence analysis platform and result generation tool. There is a minimal difference in base calling between Exatype and standard methods. Although the discrepancy has minimal impact on drug resistance interpretation, allowance of sequence editing in Exatype as RECall can significantly improve its performance.

Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon.

BackgroundAntiretroviral therapy (ART) has improved the survival of HIV infected persons. However, rapid scale-up of ART and the high HIV-1 genetic variability, has greatly influenced the emergence of drug-resistant strains. This constitutes a potential threat to achieving the UNAIDS’ 90-90-90 goals by 2020. We investigated the prevalent HIV-1 genotypes, drug resistance-associated mutations and assessed some predictors of the occurrence of these mutations.MethodsThis was a hospital-based cross-sectional study conducted between October 2010 and June 2012. Participants were consecutively enrolled from selected HIV treatment centers of the Southwest and Northwest regions of Cameroon. Viral load was determined with the automated Abbott Real-time HIV-1 m2000rt System. HIV genotyping and antiretroviral resistance mutations analysis were performed using Bayer’s HIV-1 TRUGENE™ Genotyping Kit and OpenGene DNA Sequencing system. The drug resistance mutation was interpreted with the Stanford HIV database. Epidemiological data were obtained using pre-tested semi-structured questionnaires.ResultsOf the 387 participants, 239 were successfully genotyped. The median age of these participants was 33 years (interquartile range, IQR: 28–40 years), and a majority (65.7%) were female. A total of 29.3% of the participants were receiving ART. The median duration of ART was 10.5 months (IQR: 4–17.25 months). The median CD4 count and log10 viral load of study participants were 353.5 cells/ml (IQR:145–471) and 4.89 copies/ml (IQR: 3.91–5.55) respectively. CRF02 (A/G) (69%) was the most prevalent subtype followed by G (8.2%) and F (6.7%). Overall, resistance mutations were present in 37.1% of ART-experienced and 10.7% of ART-naive patients. Nucleoside reverse transcriptase inhibitors (NRTI) mutations occurred in 30% of ART-experienced and 2.4% of ART-naïve patients, while non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations occurred in 34.2% of ART-experienced and 10.1% of -naïve patients. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most prevalent mutations. Major protease inhibitor mutations occurred in 3 (1.3%) out of the 239 sequences. The duration of ART independently predicted the occurrence of resistance mutation among ART-experienced patients.ConclusionThe high resistance to NNRTIs, which are the main support to the backbone (NRTIs) first-line antiretroviral regimen in Cameroon, has prompted the need to rollout an integrase strand transfer inhibitor regimen (containing Dolutegravir) with a higher genetic barrier to resistance as the preferred first line regimen.

Bridging the gap between HIV epidemiology and antiretroviral resistance evolution: Modelling the spread of resistance in South Africa.

The scale-up of antiretroviral therapy (ART) in South Africa substantially reduced AIDS-related deaths and new HIV infections. However, its success is threatened by the emergence of resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI). The MARISA (Modelling Antiretroviral drug Resistance In South Africa) model presented here aims at investigating the time trends and factors driving NNRTI resistance in South Africa. MARISA is a compartmental model that includes the key aspects of the local HIV epidemic: continuum of care, disease progression, and gender. The dynamics of NNRTI resistance emergence and transmission are then added to this framework. Model parameters are informed using data from HIV cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) and literature estimates, or fitted to UNAIDS estimates. Using this novel approach of triangulating clinical and resistance data from various sources, MARISA reproduces the time trends of HIV in South Africa in 2005–2016, with a decrease in new infections, undiagnosed individuals, and AIDS-related deaths. MARISA captures the dynamics of the spread of NNRTI resistance: high levels of acquired drug resistance (ADR, in 83% of first-line treatment failures in 2016), and increasing transmitted drug resistance (TDR, in 8.1% of ART initiators in 2016). Simulation of counter-factual scenarios reflecting alternative public health policies shows that increasing treatment coverage would have resulted in fewer new infections and deaths, at the cost of higher TDR (11.6% in 2016 for doubling the treatment rate). Conversely, improving switching to second-line treatment would have led to lower TDR (6.5% in 2016 for doubling the switching rate) and fewer new infections and deaths. Implementing drug resistance testing would have had little impact. The rapid ART scale-up and inadequate switching to second-line treatment were the key drivers of the spread of NNRTI resistance in South Africa. However, even though some interventions could have substantially reduced the level of NNRTI resistance, no policy including NNRTI-based first line regimens could have prevented this spread. Thus, by combining epidemiological data on HIV in South Africa with biological data on resistance evolution, our modelling approach identified key factors driving NNRTI resistance, highlighting the need of alternative first-line regimens.

The Effect of 90-90-90 on HIV-1 Incidence and Mortality in the Kingdom of Eswatini

Background: The rapid scale-up of antiretroviral therapy (ART) over the last decade has sparked considerable debate as to whether universal test and treat (UTT) can end the HIV epidemic in sub-Saharan Africa (SSA). Methods: Using the Kingdom of Eswatini as a case study, we developed a network transmission model, calibrated to capture age and gender-specific gaps in the scale-up of ART, to estimate the impact of attaining and surpassing the 90-90-90 treatment targets on HIV incidence and mortality. We compared different ART coverage scenarios to estimate reductions in incidence and mortality over time and to evaluate the potential to drive annual incidence below an epidemic control threshold of 0.1%. Findings: ART scale-up reduced HIV incidence by 43.5% (95% credible interval, 39.7 - 46.4%) and HIV mortality by 56.2% (95% CI, 54.1 - 58.9%) among adults 15-49 years of age between 2010 and 2016, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and gender, adult HIV incidence would fall to 1.1% (95% CI: 0.87 - 1.3%), 2.0% (95% CI: 1.5 - 2.5%) among women, and 0.9% (95% CI: 0.7 - 1.2%) among men by 2030. Achieving the 90-90-90 targets by age and gender would further reduce incidence in individuals 15-24 years of age, 17.4% (95% CI, 7.3 - 26.1%) additional incidence reduction between 2016 and 2013, with only modest additional reductions in adults overall. Achieving 100% ART initiation, an upper bound of treatment effect, would reduce adult HIV incidence to 0.7% (95% CI: 0.6 - 0.9%) by 2030 and 0.5% (95% CI: 0.3 - 0.6%) by 2050. Interpretation: Scale-up of ART over the last decade has already contributed to substantial reductions in HIV incidence and mortality. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures. Funding Statement: Support provided from the Global Good Fund and the Bill and Melinda Gates Foundation. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Not required.

Can differentiated care models solve the crisis in HIV treatment financing? Analysis of prospects for 38 countries in sub-Saharan Africa.

Introduction: Rapid scale-up of antiretroviral therapy (ART) in the context of financial and health system constraints has resulted in calls to maximize efficiency in ART service delivery. Adopting differentiated care models (DCMs) for ART could potentially be more cost-efficient and improve outcomes. However, no study comprehensively projects the cost savings across countries. We model the potential reduction in facility-level costs and number of health workers needed when implementing two types of DCMs while attempting to reach 90-90-90 targets in 38 sub-Saharan African countries from 2016 to 2020.Methods: We estimated the costs of three service delivery models: (1) undifferentiated care, (2) differentiated care by patient age and stability, and (3) differentiated care by patient age, stability, key vs. general population status, and urban vs. rural location. Frequency of facility visits, type and frequency of laboratory testing, and coverage of community ART support vary by patient subgroup. For each model, we estimated the total costs of antiretroviral drugs, laboratory commodities, and facility-level personnel and overhead. Certain groups under four-criteria differentiation require more intensive inputs. Community-based ART costs were included in the DCMs. We take into account underlying uncertainty in the projected numbers on ART and unit costs.Results: Total five-year facility-based ART costs for undifferentiated care are estimated to be US$23.33 billion (95% confidence interval [CI]: $23.3–$23.5 billion). An estimated 17.5% (95% CI: 17.4%–17.7%) and 16.8% (95% CI: 16.7%–17.0%) could be saved from 2016 to 2020 from implementing the age and stability DCM and four-criteria DCM, respectively, with annual cost savings increasing over time. DCMs decrease the full-time equivalent (FTE) health workforce requirements for ART. An estimated 46.4% (95% CI: 46.1%–46.7%) fewer FTE health workers are needed in 2020 for the age and stability DCM compared with undifferentiated care.Conclusions: Adopting DCMs can result in significant efficiency gains in terms of reduced costs and health workforce needs, even with the costs of scaling up community-based ART support under DCMs. Efficiency gains remained flat with increased differentiation. More evidence is needed on how to translate analyzed efficiency gains into implemented cost reductions at the facility level.

Short Communication: Population-Based Surveillance of HIV-1 Drug Resistance in Cameroonian Adults Initiating Antiretroviral Therapy According to the World Health Organization Guidelines.

With ongoing earlier enrollment on and rapid scale-up of antiretroviral therapy (ART) in Cameroon, there are increasing risks of transmitted HIV drug resistance (HIVDR) at population levels. We, therefore, evaluated the threshold of HIVDR in a population initiating ART, to inform on the effectiveness of first-line regimens, considering HIV-1 diversity, plasma viral load (PVL), and CD4-based disease progression. A total of 53 adults [median (interquartile range, IQR) CD4: 162 cell/mm(3) (48-284); median (IQR) PVL: 5.34 log10 RNA (4.17-6.42) copies/ml] initiating ART in 2014 at the Yaoundé Central Hospital were enrolled for HIV-1 protease-reverse transcriptase sequencing. Drug resistance mutations (DRMs) were interpreted using the 2009 World Health Organization (WHO) list versus the Stanford HIVdb algorithm version 7.0. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. Prevailing clade was CRF02_AG (71.70%). Based on Stanford HIVdb, a slightly higher proportion of patients with DRMs were found among ones infected with CRF02_AG than in those non-CRF02_AG infected (7.89% vs. 6.67%, p = 1.000), with lower PVL (7.69% <5.5 vs. 0% ≥5.5 log10 RNA copies/ml, p = .488) and with higher CD4 counts (9.52% CD4 ≥200 vs. 3.33% CD4 <200 cells/mm(3), p = .749). Thresholds of DRMs suggest that standard first-line regimens currently used in Cameroon may remain effective at population levels, despite scale-up of ART in the country, pending adherence, and closed virological monitoring. With an intent-to-diagnose approach, the discrepant levels of DRMs support using Stanford HIVdb to evaluate initial ART, while revising the WHO list for surveillance.

The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020.

BackgroundThe World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available.Methods and FindingsCurrent coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries’ current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS “90-90-90” ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead.We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President’s Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion.The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data.ConclusionsThe projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be “game changers” that allow more people to be on ART with the resources available.

P16.12 Optimisation hiv investment in swaziland: modelling high-impact interventions

Introduction Swaziland has the highest global HIV prevalence with an estimated 27% of people aged 15–49 living with HIV. To address this issue, the Government aimed to optimise HIV investment by assessing the impact of key interventions. Methods We used Optima to assess the impact of moderate- and high-level scale-up of five interventions: scaling-up antiretroviral therapy (ART) coverage to 65% (at CD4 count 3 ) by 2020 and 75% by 2030 (moderate scale-up) or 85% by 2020 and 90% by 2030 (high-level scale-up), voluntary medical male circumcision (VMMC) to 55% by 2018 (moderate) or 45% by 2015 and 70% by 2018 (high-level) for males aged 10−49, prevention of mother-to-child transmission to 90% (moderate) or 95% (high-level) by 2018, tuberculosis/HIV co-treatment to 75% by 2015, 85% by 2018, and 90% by 2030 (moderate) or similar targets for high-level scale-up except with 95% coverage by 2030, and implementation of conditional cash transfers (CCT) to 60% (moderate) or 95% (high-level) by 2018 for women aged 15–24. Data were provided by the Swaziland Government for general and key populations disaggregated by age and sex for 2000−2013. Results By 2030, compared to current coverage, it is possible to reduce new infections by 27% and AIDS-related deaths by 12% (moderate scale-up) or by 49% and 24%, respectively, with high-level scale-up. The highest impact interventions are ART, VMMC, and CCT. The discounted cumulative additional program cost of these combined interventions was US$74 million with an incremental cost-effectiveness ratio of US$2,700 per infection averted (for moderate scale-up) and US$309 million with an incremental cost-effectiveness ratio of US$6,300 per infection averted (for high level scale-up). Conclusion Rapid scale-up of ART and VMMC, as well as implementation of CCT for women aged 15–24 showed the greatest impact on reducing new HIV infections and AIDS-related deaths in Swaziland. Disclosure of interest statement No conflicts of interest.

Temporal trends in TB notification rates during ART scale-up in Cape Town: an ecological analysis.

IntroductionAlthough antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two-thirds, the population-level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10-year period of expanding ART.MethodsAnnual Cape Town TB notifications were used as numerators and mid-year Cape Town populations as denominators. HIV-stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub-district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub-district (numbers on ART).ResultsFrom 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14–17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV-positive (21% (95% CI, 19–23%)) than the HIV-negative (9% (95% CI, 7–11%)) population. The number of HIV-positive TB notifications decreased mainly among 0- to 4- and 20- to 34-year-olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p<0.001). Sub-district antenatal HIV seroprevalence differed (10–33%) as did numbers on ART (9–29 thousand). Across sub-districts, infant HIV-positive TB decreased consistently whereas adult decreases varied.ConclusionsHIV-positive TB notification rates declined during a period of rapid scale-up of ART. Nevertheless, both HIV-positive and HIV-negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation.

Low prevalence of transmitted drug resistance of HIV-1 during 2008-2012 antiretroviral therapy scaling up in Southern Vietnam.

The recent expansion of antiretroviral therapy (ART) program in resource-limited setting has raised concern about possible transmission of drug resistance (TDR). We assessed the prevalence of TDR over a 5-year period among treatment-naive individuals in Southern Vietnam during rapid ART scale-up. Drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Ho Chi Minh City were evaluated prospectively from 2008 to 2012 by HIV-1 pol gene sequencing. TDR was defined according to the World Health Organization list for surveillance of transmitted HIV-1 drug resistance in 2009. Pol sequence was obtained in 1389 individuals (median age: 30 years, males: 52.3%). Risks of HIV-1 infection included heterosexual contact in 60.7%, injection drug use in 22.4% and both 5.2%. The majority was infected with CRF01_AE (97%), whereas 19 were infected with subtype B. Over the 5-year study period, TDR was detected in 58 individuals (4.18%): 28 (2.02%) against nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 19 (1.37%) against nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 15 (1.08%) against protease inhibitors (PIs), including 4 (0.29%) against both NRTIs and NNRTIs. The most common TDR was K103N (0.5%) for NNRTI. The annual prevalence of TDR remained low to moderate (2008: 2.4%; 2009: 5.2%; 2010: 5.48%; 2011: 2.72%; 2012: 5.36%), and there was no clear trend over time. There was no increase in TDR prevalence in Southern Vietnam during and after the 2008-2012 rapid scale up of ART.

Changes in Population HIV RNA Levels in Mbarara, Uganda, During Scale-up of HIV Antiretroviral Therapy Access

In a rural Ugandan community scaling up antiretroviral therapy (ART), we sought to determine if population-based HIV RNA levels [population viral load (VL)] decreased from 2011 to 2012. Serial cross-sectional analyses (May 2011 and May 2012) of a defined study community of 6300 persons in a district with HIV prevalence of 8%. We measured HIV-1 RNA (VL) levels on all individuals testing positive for HIV during a 5-day high-throughput multidisease community health campaign in May 2012 that recruited two-thirds of the population. We aggregated individual-level VL results into population VL metrics including the proportion of individuals with an undetectable VL and compared these VL metrics to those we previously reported for this geographic region in 2011. In 2012, 223 of 2179 adults were HIV-seropositive adults (10%). Overall, among 208 of 223 HIV-seropositive adults in whom VL was tested, 53% had an undetectable VL [95% confidence interval (CI): 46 to 60], up from 37% (95% CI: 30 to 45; P = 0.02) in 2011. Seven (3%) individuals had a VL of >100,000 copies/mL in 2012, down from 21 (13%) in 2011 (P = 0.0007). Mean log (VL) (geometric mean) was 3.18 log (95% CI: 3.06 to 3.29 log) in 2012, down from 3.62 log (95% CI: 3.46 to 3.78 log) in 2011 (P < 0.0001). Similar reductions in population VL were seen among men and women. Reductions in population VL metrics and a substantial increase in the proportion of persons with an undetectable VL were observed in a rural Ugandan community from 2011 to 2012. These findings from a resource-limited setting experiencing rapid ART scale-up may reflect a population-level effectiveness of expanding ART access.

Costing Analysis of National HIV Treatment and Care Program in Vietnam

Vietnam achieved rapid scale-up of antiretroviral therapy (ART), although external funds are declining sharply. To achieve and sustain universal access to HIV services, evidence-based planning is essential. To date, there had been limited HIV treatment and care cost data available in Vietnam. Cost data of outpatient and inpatient HIV care were extracted at 21 sentinel facilities (17 adult and 4 pediatric) that epitomize the national program. Step-down costing for administration costs and bottom-up resource costing for drugs, diagnostics, and labor were used. Records of 1401 adults and 527 pediatric patients were reviewed. Median outpatient care costs per patient-year for pre-ART, first year ART, later year ART, and second-line ART were US $100, US $316, US $303, and US $1557 for adults; and US $171, US $387, US $320, and US $1069 for children, respectively. Median inpatient care cost per episode was US $162 for adults and US $142 for children. Non-antiretroviral (ARV) costs in adults at stand-alone facilities were 44% (first year ART) and 24% (later year ART) higher than those at integrated facilities. Adults who started ART with CD4 count ≤100 cells per cubic millimeter had 47% higher non-ARV costs in the first year ART than those with CD4 count >100 cells per cubic millimeter. Adult ARV drug costs at government sites were from 66% to 85% higher than those at donor-supported sites in the first year ART. The study found that HIV treatment and care costs in Vietnam are economical, yet there is potential to further promote efficiency through strengthening competitive procurement, integrating HIV services, and promoting earlier ART initiation.

Current status of HIV treatment in Asia and the Pacific region

Asia and the Pacific represent a diverse group of nations facing HIV epidemic profiles of differing severity. Compared to other parts of the world, the burden of HIV disease is high in this region because of its large populations. At the end of 2011, 5million people were living with HIV in Asia and the Pacific. This accounted for 15% of people living with HIV worldwide. The prevalence of people living with HIV, as well as access to HIV treatment and care, varies widely between countries. Differences between high-income economies and the rest of the continent are remarkable. Many high-income countries provide antiretroviral therapy (ART) to their citizens. Middle- and low-income countries have rapid ART scale-up and are dependent on international funding. This may compromise the sustainability of ART availability. In addition, lack of access to second- and third-line therapy remains a problem in many countries. The global goal of achieving universal access to ART by 2015 requires mainly low- and middle-income countries to be targeted. Regional policy should be developed in order to identify new infections in key populations, to start earlier treatment, to retain patients in care and to maintain funding.

Barriers and facilitators of retention in HIV care and treatment services in Iringa, Tanzania: the importance of socioeconomic and sociocultural factors

Although an increasing number of people living with HIV (PLHIV) in sub-Saharan Africa are benefiting from the rapid scale-up of antiretroviral therapy (ART), retention in HIV care and treatment services remains a major concern. We examined socioeconomic and sociocultural barriers and potential facilitators of retention in ART in Iringa, Tanzania, a region with the second highest prevalence of HIV in the country. In 2012, 116 in-depth interviews were conducted to assess community members' perceptions, barriers and facilitators of HIV treatment in Iringa, including key informants, persons at heightened risk for infection, and HIV service-delivery users. Data were transcribed, translated, entered into Atlas.ti, coded, and analyzed for key themes. In order to provide the full range of perspectives across the community on issues that may affect retention, we report findings from all 116 participants, but draw on verbatim quotes to highlight the experiences of the 14 PLHIV who reported that they were receiving HIV care and treatment services. Despite the growing availability of HIV care and treatment services in Iringa, participants reported significant barriers to retention, including lack of knowledge and misperceptions of treatment, access problems that included difficulties in reaching distant clinics and pervasive poverty that left PLHIV unable to cope with out-of-pocket costs associated with their care, persistent stigmatization of PLHIV and frequent reliance on alternative healing systems instead of biomedical treatment. Positive perceptions of the efficacy of ART, improved ART availability in the region, improved access to care through supplemental aid, and social support were perceived to enhance treatment continuation. Our findings suggest that numerous socioeconomic and sociocultural barriers inhibit retention in HIV care and treatment services in this setting. Intervention strategies that improve ART accessibility, incorporate supplemental aid, enhance social support, reduce stigma, and develop partnerships with alternative healers are needed to improve HIV-related outcomes.

Beyond first-line HIV treatment regimens

With the availability of antiretroviral drugs in resource-limited settings, there is a rapid scale-up of antiretroviral therapy in developing countries. The review focuses on the issues faced while patients are on first-line antiretroviral therapy in the absence of viral load monitoring, and the availability and progress of the second-line antiretroviral drugs and the salvage regimens in resource-limited settings. There is an urgent need for low-cost, low-tech viral load monitoring in resource-limited settings. Fixed-dose combination of antiretrovirals for first-line and second-line therapy will result in better effectiveness. There is a need for newer antiretroviral drugs in resource-limited settings.

Limited Evolution but Increasing Trends of Primary Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations in Therapy-Naive HIV-1-Infected Individuals in India

After the rapid scale-up of antiretroviral therapy (ART) in resource-limited settings, surveillance of primary drug resistance mutations (DRMs) among ART-naive individuals has important public health benefits. Although a highly successful national ART programme initiated by the Government of India exists, data on the prevalence of primary DRMs is scarce. The objective of the study is to estimate the prevalence, pattern and spectrum of population-based primary DRMs in therapy-naive HIV-1-infected individuals using clinical strains and database sequences from seven HIV prevalent states of India. Drug resistance genotyping was performed on either plasma RNA or whole-blood genomic DNA using a validated in-house method on 170 HIV-1-positive therapy-naive individuals. An additional 679 database-derived sequences from four other states were included in the analysis. The WHO-recommended list of mutations (SDRM_2009) for nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were used for interpretation of DRMs. Trends of primary DRMs before and after the ART rollout were studied. The overall prevalence of primary DRMs was 2.6% in the selected states of India when clinical isolates as well as database-derived sequences were combined. Common mutations included T69D and D67N (NRTI mutations), and L100I, K101E, K103N and Y181C (NNRTI mutations). There was a significant increase in NNRTI mutations over time. The overall DRM prevalence in this study was low. However, an increasing trend in primary NNRTI resistance has been observed during the past decade. Establishment of HIV drug resistance threshold surveillance will be useful in understanding further trends of transmitted resistance.

Management Issues of HIV Infection in Poor Resource Setting Due to Unavailability of Drug Sensitivity Testing

Despite the obvious benefits that rapid scale-up of antiretroviral therapy (ART) has had on cases of human immunodeficiency virus (HIV), treatment failure that is mostly associated with the emergence of HIV drug resistance still remains a major challenge. Index case is a stage 4 HIV patient who failed multiple ART, including nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) and protease inhibitors (PIs). His clinical and immunological markers continued to fail despite completion of anti tuberculosis drugs, adequate nutrition, and treatment for opportunistic infections. This case indicates an emerging need to consider providing facility for HIV drug sensitivity testing at various sites in order to select appropriate second line antiretrovirals that would be of benefit to a patient. DOI: http://dx.doi.org/10.3126/jnps.v33i2.7699 J Nepal Paediatr Soc. 2013; 33(2):141-143

Surveillance of Transmitted HIV Drug Resistance in Antiretroviral-Naive Patients Aged less than 25 Years, in Bangkok, Thailand

Emergence of transmitted HIV drug resistance (TDR) is a concern after global scale-up of antiretroviral therapy (ART). World Health Organization had developed threshold survey method for surveillance of TDR in resource-limited countries. ART in Thailand has been scaling up for >10 years. To evaluate the current TDR in Thailand, a cross-sectional study was conducted among antiretroviral-naive HIV-infected patients aged <25 years who newly visited infectious disease clinic in a university hospital, in 2011. HIV genotypic-resistance test was performed. World Health Organization 2009 surveillance drug-resistance mutations were used to define TDR. Of 50 patients, the prevalence of TDR was 4%. Of 2 patients with TDR, 1 had K103N and the other had Y181C mutations. Transmitted HIV drug resistance is emerging in Thailand after a decade of rapid scale-up of ART. Interventions to prevent TDR at the population level are essentially needed in Thailand. Surveillance for TDR in Thailand has to be regularly performed.