HIV Drug Resistance Prevention Research Articles

Transmitted drug resistance and transmission clusters among ART-naïve HIV-1-infected individuals from 2019 to 2021 in Nanjing, China.

Transmitted drug resistance (TDR) is an increasingly prevalent problem worldwide, which will significantly compromise the effectiveness of HIV treatments. However, in Nanjing, China, there is still a dearth of research on the prevalence and transmission of TDR among ART-naïve HIV-1-infected individuals. This study aimed to understand the prevalence and transmission of TDR in Nanjing. A total of 1,393 participants who were newly diagnosed with HIV-1 and had not received ART between January 2019 and December 2021 were enrolled in this study. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR amplification. Genotypes, TDR and transmission cluster analyses were conducted using phylogenetic tree, Stanford HIV database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with TDR. A total of 1,161 sequences were successfully sequenced, of which CRF07_BC (40.6%), CRF01_AE (38.4%) and CRF105_0107 (6.3%) were the main HIV-1 genotypes. The overall prevalence of TDR was 7.8%, with 2.0% to PIs, 1.0% to NRTIs, and 4.8% to NNRTIs. No sequence showed double-class resistance. Multivariate logistic regression analysis revealed that compared with CRF01_AE, subtype B (OR = 2.869, 95%CI: 1.093-7.420) and female (OR = 2.359, 95%CI: 1.182-4.707) were risk factors for TDR. Q58E was the most prevalent detected protease inhibitor (PI) -associated mutation, and V179E was the most frequently detected non-nucleoside reverse transcriptase inhibitor (NNRTI) -associated mutation. A total of 613 (52.8%) sequences were segregated into 137 clusters, ranging from 2 to 74 sequences. Among 44 individuals with TDR (48.4%) within 21 clusters, K103N/KN was the most frequent TDR-associated mutation (31.8%), followed by Q58E/QE (20.5%) and G190A (15.9%). Individuals with the same TDR-associated mutations were usually cross-linked in transmission clusters. Moreover, we identified 9 clusters in which there was a transmission relationship between drug-resistant individuals, and 4 clusters in which drug-resistant cases increased during the study period. The overall prevalence of TDR in Nanjing was at a moderate level during the past 3 years. However, nearly half of TDR individuals were included in the transmission clusters, and some drug-resistant individuals have transmitted in the clusters. Therefore, HIV drug-resistance prevention, monitoring and response efforts should be sustained and expanded to reduce the prevalence and transmission of TDR in Nanjing.

Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling

BackgroundRetention on lifelong antiretroviral therapy (ART) is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR), especially in resource-limited settings (RLS). In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months.MethodsUsing a systematic random sampling, a survey was conducted in the ten regions (56 sites) of Cameroon, within the “reporting period” of October 2013–November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%), fair (85–75%), poor (<75); and factors with p-value < 0.01 were considered statistically significant.ResultsMajority (74.4%) of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349); only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2%) vs. management units (66.8%), p < 0.0001; male (57.1%) vs. women (62.0%), p = 0.007; and with WHO clinical stage I (63.3%) vs. other stages (55.6%), p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730) nor for immune status (CD4351–500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077).ConclusionsPoor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1991-3) contains supplementary material, which is available to authorized users.

An assessment of the relationship between the World Health Organization HIV drug resistance early warning indicators and HIV drug resistance acquisition.

The World Health Organization (WHO)'s HIV drug resistance (HIVDR) early warning indicators (EWIs) measure antiretroviral therapy (ART)-site factors associated with HIVDR prevention, without HIVDR laboratory testing. We assessed the relationship between EWIs and HIVDR acquisition using data from British Columbia, Canada. Eligible patients were ART-naïve, were ≥19years old, had initiated ART between 1 January 2000 and 31 December 2012, had ≥15months of follow-up, and were without transmitted HIVDR. Patients were followed for acquired HIVDR until 31 March 2014, the last contact date, or death. We built logistic regression models to assess the associations and predictive ability of individual indicators and of the EWI Score (the number of indicators for which a patient did not meet the criteria) on HIVDR acquisition (to any class of HIVDR, lamivudine (3TC)/emtricitabine (FTC), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs)]). All explored EWIs were associated with at least one class of HIVDR, with the exception of 'ART prescribing practices'. We observed a dose-response relationship between acquiring HIVDR to any antiretroviral class and an increasing EWI score in our predictive logistic regression model. The area under the curve was 0.848 (excellent discrimination). The adjusted odds ratios for acquiring any class of HIVDR for an EWI score of 1, 2 and ≥3 versus 0 were 2.30 [95% confidence Interval (CI) 1.21-4.38], 3.35 (95% CI: 1.86-6.03) and 7.26 (95% CI: 4.18-12.61), respectively. Several EWIs were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available.

Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.

BackgroundZimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010.MethodsParticipants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites.ResultsA total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm3 with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2–7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002).ConclusionsThe results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda.

BackgroundWith the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).MethodsWe implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points.ResultsOf the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14).ConclusionStrengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study.

The emergence of HIV-1 drug resistance mutations has mainly been linked to the duration and composition of antiretroviral treatment (ART), as well as the level of adherence. This study reports the incidence and pattern of acquired antiretroviral drug resistance mutations and long-term outcomes of ART in a prospective cohort from Northwest Ethiopia. Two hundred and twenty HIV-1C infected treatment naïve patients were enrolled and 127 were followed-up for up to 38 months on ART. ART initiation and patients’ monitoring was based on the WHO clinical and immunological parameters. HIV viral RNA measurement and drug resistance genotyping were done at baseline (N = 160) and after a median time of 30 (IQR, 27–38) months on ART (N = 127). Viral suppression rate (HIV RNA levels ≤ 400 copies/ml) after a median time of 30 months on ART was found to be 88.2% (112/127), which is in the range for HIV drug resistance prevention suggested by WHO. Of those 15 patients with viral load >400 copies/ml, six harboured one or more drug resistant associated mutations in the reverse transcriptase (RT) region. Observed NRTIs resistance associated mutations were the lamivudine-induced mutation M184V (n = 4) and tenofovir associated mutation K65R (n = 1). The NNRTIs resistance associated mutations were K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each). Thymidine analogue mutations and major drug resistance mutations in the protease (PR) region were not detected. Most of the patients (13/15) with virologic failure and accumulated drug resistance mutations had not met the WHO clinical and/or immunological failure criteria and continued the failing regimen. The incidence and pattern of acquired antiretroviral drug resistance mutations is lower and less complex than previous reports from sub Saharan Africa countries. Nevertheless, the data suggest the need for virological monitoring and resistance testing for early detection of failure. Moreover, adherence reinforcement will contribute to improving overall treatment outcomes.

Trends in Prevalence of HIV-1 Drug Resistance in a Public Clinic in Maputo, Mozambique.

BackgroundAn observational study was conducted in Maputo, Mozambique, to investigate trends in prevalence of HIV drug resistance (HIVDR) in antiretroviral (ART) naïve subjects initiating highly active antiretroviral treatment (HAART).Methodology/Principal FindingsTo evaluate the pattern of drug resistance mutations (DRMs) found in adults on ART failing first-line HAART [patients with detectable viral load (VL)]. Untreated subjects [Group 1 (G1; n=99)] and 274 treated subjects with variable length of exposure to ARV´s [6–12 months, Group 2 (G2;n=93); 12-24 months, Group 3 (G3;n=81); >24 months (G4;n=100)] were enrolled. Virological and immunological failure (VF and IF) were measured based on viral load (VL) and T lymphocyte CD4+ cells (TCD4+) count and genotypic resistance was also performed. Major subtype found was C (untreated: n=66, 97,06%; treated: n=36, 91.7%). Maximum virological suppression was observed in G3, and significant differences intragroup were observed between VF and IF in G4 (p=0.022). Intergroup differences were observed between G3 and G4 for VF (p=0.023) and IF between G2 and G4 (p=0.0018). Viral suppression (<50 copies/ml) ranged from 84.9% to 90.1%, and concordant VL and DRM ranged from 25% to 57%. WHO cut-off for determining VF as given by 2010 guidelines (>5000 copies/ml) identified 50% of subjects carrying DRM compared to 100% when lower VL cut-off was used (<50 copies/ml). Length of exposure to ARVs was directly proportional to the complexity of DRM patterns. In Mozambique, VL suppression was achieved in 76% of individuals after 24 months on HAART. This is in agreement with WHO target for HIVDR prevention target (70%).ConclusionsWe demonstrated that the best way to determine therapeutic failure is VL compared to CD4 counts. The rationalized use of VL testing is needed to ensure timely detection of treatment failures preventing the occurrence of TDR and new infections.

Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia.

The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors. Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR). Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province, China.

Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF)07_BC variant in Sichuan, China. This study examined 375 plasma samples from patients with HIV-1 who were infected with the CRF07_BC strain, including 104 drug-naive participants and 271 in whom antiretroviral therapy (ART) had failed. Only one participant in the drug-naive group had a drug-resistance mutation (M46L), compared with 31.73% of those in whom ART had failed. Further analysis showed that 19.56% of strains contained mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) alone, 0.74% were resistant to nucleoside reverse transcriptase inhibitors (NRTIs) alone, and 11.44% were dual-resistant to both NRTIs and NNRTIs. The most common mutation in the ART-failure group was M184V (35.88%), K103N (45.01%), Y181C (17.33%), and G190S/A (15.88%). The percentages of HIV-1 strains resistant to lamivudine, emtricitabine, efavirenz, etravirine, and nevirapine were 10.70%, 10.70%, 28.04%, 7.75%, and 26.20%, respectively. To explore site variants possibly related to drug resistance, variations in the ancestor/consensus CRF07_BC sequences from the therapy-naive and ART-failure groups were compared, and seven mutations at six positions were identified as being significantly differently distributed between the two groups (p<0.05). Detailed sequence data will provide information on CRF07_BC genetic characterizations, and improve our understanding of antiretroviral susceptibility and the evolution of drug-resistance mutations. This will be valuable in developing and implementing local public-health approaches for HIV drug-resistance prevention and treatment.

Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation.

Introduction. In India, 4,86,173 HIV infected patients are on first line antiretroviral therapy (ART) as of January 2012. HIV drug resistance (HIVDR) is drug and regimen-specific and should be balanced against the benefits of providing a given ART regimen. Material & Methods. The emergence of HIVDR mutations in a cohort of 100 consecutive HIV-1 infected individuals attending ART centre, on first line ART for 12 months, was studied. CD4+ T-cell counts and plasma HIV-1 RNA level were determined. Result. Out of the 100 HIV-1 infected individuals, 81 showed HIVDR prevention (HIV-1 RNA level < 1000/mL), while the remaining 19 had HIV-1 viral RNA level > 1000/mL. HIVDR genotyping was carried out for individuals with evidence of virologic failure (HIV-1 RNA level > 1000/mL). The most frequent NRTI-associated mutation observed was M184V, while K103N/S was the commonest mutation at NNRTI resistance position. Conclusion. Our study has revealed the emergence of HIVDR in HIV-1 infected patients at the end of 12 months of first line ART initiation. For NRTIs, the prevalence of HIVDR mutations was 9% and 10% for NNRTIs. Our findings will contribute information in evidence-based decision making with reference to first and second line ART delivery and prevention of HIVDR emergence.

Low Primary and Secondary HIV Drug-Resistance after 12 Months of Antiretroviral Therapy in Human Immune-Deficiency Virus Type 1 (HIV-1)-Infected Individuals from Kigali, Rwanda

Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral–naïve HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL≤1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ≤200cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p = 0.008).Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.

Findings from the WHO/PAHO early warning indicators of HIV drug resistance monitoring system performed in Argentina

BackgroundIn the last years, WHO developed a Global Strategy for HIV Drug Resistance Prevention and Assessment using a public health approach. This strategy supports optimal functioning of treatment programs to minimize emergence of preventable HIV drug resistance and to maintain effectiveness of first‐ and second‐line ART regimens. Since 2011, Argentina has been monitoring some of the indicators of this strategy (called early warning indicators [EWIs]). The aim of this study was to analyze the outcomes measured during the mentioned year.MethodsBased on the availability of information in the hospitals’ pharmacies, where the data collection took place, and on the relevance for Argentina, some of the EWIs proposed by WHO were selected and adapted. The information is being collected since beginning of 2011, and a first analysis was performed at the end of that year. Since this was a pilot phase, 6 representative hospitals’ pharmacies participated.ResultsData are available for 4 of the sites. The data produced the following indicators: EWI 1a: Percentage of adult patients initiating ART who are prescribed a non‐recommended first‐line ART regimen (goal 0%). Site A: 22.5%; Site B: 11.1%; Site C: 0%; Site D: 2.7%. EWI 1b: Percentage of adult patients initiating ART who withdraw a non‐recommended first‐line ART regimen (goal 0%). Site A: 22.5%; Site B: 25.8%; Site C: 15.5%; Site D: 16.1%. EWI 2: Percentage of patients lost to follow‐up 12 months after ART initiation (goal less than 20%): Site A: 41.6%; Site B: 9.3%; Site C: 22.2%; Site D: 0%. EWI 4: percentage of patients who picked up prescribed ARV drugs on time (goal:&gt;90%): Site A: 39.1%; Site B: 72.4%; Site C: 44.5%; Site D: N/DConclusionsThere is a high proportion of patients in Argentina which are prescribed non‐recommended regimens, and a higher proportion withdraw these regimens from pharmacies: 75% of sites do NOT reach the goal of EWI 1a; 100% do NOT reach the goal for EWI 1b. There is also a high proportion of patients lost to follow up during the first year after treatment initiation: 50% of sites reach the goal of EWI 2. A very high proportion of patients do NOT pick‐up ART on time: none of the sites reach EWI 4 goal. The use of these indicators allowed us to visualize that there is a high proportion of patients that would be nonadherent. With these data the Directorate of AIDS will improve efforts to know better the situation, understand the causes and implement strategies to increase adherence.

Determinants of HIV Drug Resistance and Public Health Implications in Low- and Middle-Income Countries

Global scale-up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is an unprecedented public health achievement. With planned efforts of expanded ART access including earlier treatment initiation and the use of antiretroviral (ARV) drugs for prophylaxis, increasing levels of HIV drug resistance (HIVDR) are expected.Several factors may lead to selection and transmission of significant HIVDR in LMICs, which will lead to decreased population-level efficacy of standard first- and second-line ART regimens. These factors include low genetic barrier of some ARVs to resistance development, drug-drug interactions, inappropriate prescribing practices, interruption of drug supply, poor retention in care and lack of routine viral load monitoring.To maximize long-term effectiveness of available ARVs, policy makers and programme managers in LMICs should routinely monitor programme factors associated with emergence and transmission of HIVDR and implement routine HIVDR surveillance following standardized methods. When surveillance results suggest the need for action, specific public health interventions must be taken to adjust ART programme functioning to minimize further emergence and transmission of HIVDR.In this paper, we review ARV drug, HIV, patient and programme-related determinants of HIVDR. Additionally, we summarize the World Health Orgnization's global HIVDR surveillance and prevention strategy and describe resulting public health and policy implications.

The World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: Global, Regional, and Country Progress

The World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: Global, Regional, and Country Progress

Update on World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: 2004-2011

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.

Progress of implementation of the World Health Organization strategy for HIV drug resistance control in Latin America and the Caribbean

By the end of 2010, Latin America and the Caribbean (LAC) achieved 63% antiretroviral treatment (ART) coverage. Measures to control HIV drug resistance (HIVDR) at the country level are recommended to maximize the efficacy and sustainability of ART programs. Since 2006, the Pan American Health Organization has supported implementation of the World Health Organization (WHO) strategy for HIVDR prevention and assessment through regional capacity-building activities and direct technical cooperation in 30 LAC countries. By 2010, 85 sites in 19 countries reported early warning indicators, providing information about the extent of potential drivers of drug resistance at the ART site. In 2009, 41.9% of sites did not achieve the WHO target of 100% appropriate first-line prescriptions; 6.3% still experienced high rates (> 20%) of loss to follow-up, and 16.2% had low retention of patients (< 70%) on first-line prescriptions in the first year of treatment. Stock-outs of antiretroviral drugs occurred at 22.7% of sites. Haiti, Guyana, and the Mesoamerican region are planning and implementing WHO HIVDR monitoring surveys or threshold surveys. New HIVDR surveillance tools for concentrated epidemics would promote further scale-up. Extending the WHO HIVDR lab network in Latin America is key to strengthening regional lab capacity to support quality assured HIVDR surveillance. The WHO HIVDR control strategy is feasible and can be rolled out in LAC. Integrating HIVDR activities in national HIV care and treatment plans is key to ensuring the sustainability of this strategy.

Factors Associated with HIV Virologic Failure Among Patients on HAART for One Year at Three Sentinel Surveillance Sites in China

Emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of highly active antiretroviral therapy (HAART). To understand the incidence of HIVDR and estimate the proportion of potential HIVDR and its associated risk factors among the patients on HAART for one year. Antiretroviral-naïve patients ≥ 18 years old were invited to participate in this one-year prospective study from seven clinics in Yunnan, Guangxi, and Xinjiang provinces. A questionnaire and blood draw were collected at baseline and 12 month follow-up. The protocol used was modified slightly from the WHO Protocol for Surveys of HIV Drug Resistance Emerging During Treatment and Related Program Factors in Sentinel ART Sites in Resource-limited Settings. 435 subjects were included in the final analysis, with median baseline CD4 cell count 139 cells/mm3. Of the total 417 patients who fall under WHO guidelines for 'Classification of outcomes based on endpoints' (on ART at 12 months, switch, lost to follow-up, and stop), 90 (21.6%) did not have any drug resistant mutations (potential HIVDR) and 17 (4.1%) did (HIVDR, Table 2). The remaining 310 (75.3%) had a viral load <1000 copies/ml (HIVDR prevention). Among 351 patients retained at 12 months, 41 (11.7%) had a viral load >1000 copies/ml.Patients who self-reported missing doses in the previous month were 6.2 fold (95% CI 2.5-15.7) more likely to fail than those who did not. and those from Xinjiang were 12.1 fold (95% CI 5.2-28.1) more likely to fail compared to those from Yunnan and Guangxi. Why Xinjiang was associated with virologic failure was not clear but may be related to the demographics of the participants from Xinjiang, being significantly more IDUs, poorer, and less adherent than those from Yunnan and Guangxi. Although successful virologic outcomes were seen in the vast majority (75.3%) of those treated at one year, virologic failure continues to be a problem particularly among those less adherent and from Xinjiang. Additional data are needed to understand the generalizability of these results, particularly those related to Xinjiang. For IDUs, enhancing adherence to HAART and considering the treatment of drug addiction as an integral part of the treatment for HIV infection should be considered. As China's National Free Antiretroviral Treament Program continues to mature and improve, ramping up treatment in these settings may be important considerations to the long-term success of the program.

World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites

The World Health Organization (WHO) estimates that &gt;2 million people will have started antiretroviral therapy (ART) by the end of 2006. As the development of some HIV drug resistance (HIVDR) is inevitable in populations taking ART, the emergence of HIVDR must be balanced against the benefits of providing ART, including improved health outcomes and decreased HIV/AIDS-associated morbidity and mortality. ART programmes should operate to minimize the emergence of HIVDR in populations receiving therapy and HIVDR itself must be monitored to ensure ongoing regimen efficacy. ART regimens in resource-limited settings are usually selected at the national level following a public health approach: generally only one first-line regimen with alternate regimen(s) incorporating within-class drug substitutions are available in the public sector. The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites. The WHO surveys monitor HIVDR prevention in sentinel sites by utilizing a standardized, minimum-resource prospective survey methodology to assess the success of adult and paediatric ART sites in preventing HIVDR emergence during the first year of ART. The surveys also identify associated factors that can be addressed at the level of the ART site or programme. WHO HIVDR monitoring surveys are designed to be integrated easily into a country's ongoing, routine HIV-related evaluation activities. Performed regularly at representative sites, the data generated will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.

The requirement for surveillance of HIV drug resistance within antiretroviral rollout in the developing world

To describe surveillance measures to inform HIV drug-resistance prevention, as part of the public health approach to antiretroviral therapy in developing countries. Neither HIV drug-resistance transmission nor its emergence in treatment is routinely assessed in the developing world, but routine methods should be part of antiretroviral therapy scale-up. Mathematical modelling and experience in resource-rich countries suggest HIV drug-resistance transmission will increase as antiretroviral therapy coverage increases, but its rise will be limited initially. Transmission surveys should begin in geographic areas in each country where antiretroviral therapy coverage is widespread. Reports from resource-limited countries suggest that antiretroviral therapy programs are as effective as in resource-rich countries, which should limit HIV drug resistance if effectiveness is maintained with antiretroviral therapy expansion. Surveillance of HIV drug resistance emerging in treatment and other factors will support implementation of prevention measures on a population level. Standardized surveillance of transmitted and treatment-associated HIV drug resistance is critical to the success of antiretroviral therapy expansion in developing countries. Routine assessment of prescribing practices, availability of and access to appropriate regimens for adults and children, antiretroviral drug supply continuity, and measures to prevent HIV transmission will supply critical information for HIV drug-resistance prevention.