Second-line Antiretroviral Therapy Regimens Research Articles

Confronting the human papillomavirus-HIV intersection: Cervical cytology implications for Kenyan women living with HIV.

High-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer, leading to over 311 000 global deaths, mainly in low- and middle-income countries. Kenyan women living with HIV (WLHIV) face a disproportionate burden of HR-HPV. We determined the prevalence of HR-HPV infections and their association with cervical cytology findings among Kenyan WLHIV. We conducted a cross-sectional study among WLHIV attending the HIV care and treatment clinic at the Kenyatta National Hospital (KNH), Kenya's national referral hospital. Study nurses collected a cervical sample with a cytobrush for HR-HPV genotyping using Gene Xpert® assays and HPV Genotypes 14 Real-TM Quant V67-100FRT. Bivariate analysis explored the associations. We enrolled 647 WLHIV (mean age of 42.8 years), with 97.2% on antiretroviral therapy (ART) and 79% with a suppressed viral load (< 50 copies/mL plasma). The prevalence of any and vaccine-preventable HR-HPV was 34.6% and 29.4%, respectively, with HPV 52 being the most common genotype (13.4%). Among WLHIV with HR-HPV infections, 21.4% had abnormal cervical cytology. Women with multiple HR-HPV infections were more likely to have abnormal cytology compared to those with single HR-HPV infections (34.9 vs 9.3%, adjusted odds ratio [aOR] = 6.2, 95% confidence interval [CI]: 2.7-14.1, P = 0.001). Women with HR-HPV infection (single or multiple) were more likely to be on the second-line ART regimen compared to those without HR-HPV infections (53.1% vs 46.7%, aOR = 2.3, 95% CI: 1.3-4.1, P = 0.005). Among WLHIV at KNH, abnormal cytology was common and more frequent among women with multiple HR-HPV infections.

Incidence of switching to second-line antiretroviral therapy and its predictors among children on antiretroviral therapy at general hospitals, Northern Ethiopia: A survival analysis.

With expanding access to pediatric antiretroviral therapy, several patients in the developing world were switched to the second-line regimen, and some require third-line medications. A delay in a second-line switch is associated with an increased risk of mortality and other undesired therapeutic outcomes, drives up program costs, and challenges the pediatric antiretroviral therapy service. Nevertheless, there remain limited and often conflicting estimates on second-line antiretroviral therapy use during childhood, especially in resource-limited settings like Ethiopia. Thus, this study intended to determine the incidence and predictors of switching to second-line antiretroviral therapy among children. A retrospective cohort study was conducted by reviewing records of 424 randomly selected children on first-line antiretroviral therapy from January 2014 to December 2018 at public hospitals in the Central and Southern Zones of Tigray, Northern Ethiopia. Data were collected using extraction tool; entered into Epi-data; cleaned, and analyzed by STATA version-14. Kaplan-Meier curve, log-rank test, and life table were used for data description and adjusted hazard ratios and p-value for analysis by Cox proportional hazard regression. Variables at a P-value of ≤0.20 in the bi-variable analysis were taken to multivariable analysis. Finally, statistical significance was declared at a P-value of ≤0.05. Analysis was conducted on 424 charts with a total person-time observation of 11686.1 child-months and an incidence switch rate of 5.6 (95%CI: 4.36-7.09) per 1000 child-month-observations. Being orphan [AHR = 2.36; 95%CI: 1.10-5.07], suboptimal adherence [AHR = 2.10; 95% CI: 1.12-3.92], drug toxicity [AHR = 7.05; 95% CI: 3.61-13.75], advanced latest clinical stage [AHR = 2.75; 95%CI: 1.05-7.15], and tuberculosis co-infection at baseline [AHR = 3.08; 95%CI: 1.26-7.51] were significantly associated with switch to second-line antiretroviral therapy regimen. Moreover, a long duration of follow-up [AHR = 0.75; 95% CI: 0.71-0.81] was associated with decreased risk of switching. Hence, it is better to prioritize strengthening the focused evaluation of tuberculosis co-infection and treatment failure with continuous adherence monitoring. Further research is also needed to evaluate the effect of drug resistance.

Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1.

Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals. In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability. DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group. High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study

The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania. We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania. Eligible participants were pregnant women of any age with HIV, and later their infants, who enrolled in routine health-care services for the prevention of vertical transmission. We prospectively followed up mother-infant pairs at routine monthly visits until 18 months post partum and extracted data from the care and treatment clinic (CTC2) database, a national electronic database that stores patient-level HIV care and treatment clinic data. The primary outcome was time from birth to HIV diagnosis, defined as a positive infant HIV DNA PCR or antibody test from age 18 months. We used the Kaplan-Meier method to estimate cumulative risk of vertical transmission by 18 months post partum and Cox proportional hazards regression with shared frailties to account for potential clustering in health facilities to evaluate predictors of transmission. Between Jan 1, 2015, and Dec 31, 2017, 22 930 pregnant women with HIV (median age 30 years, IQR 25-34) enrolled on a care programme. After excluding 9140 (39·9%) women and 539 (2·4%) infants with missing outcome data, 13 251 (59·0%) mother-infant pairs were analysed, of whom 6072 (45·8%) women were already on ART before pregnancy. By 18 months post partum, 159 (1·2%) of 13 251 infants were diagnosed with HIV, equivalent to a risk of vertical transmission of 1·4% (95% CI 1·2-1·6). In the complete case analysis, the rates of vertical transmission were higher among women who enrolled in the third trimester of pregnancy than among those who enrolled in the first trimester (adjusted hazard ratio 3·01, 95% CI 1·59-5·70; p=0·0003), among women with advanced HIV disease than among those with early-stage disease (1·89, 1·22-2·93; p=0·0046), and among women who were on a second-line ART regimen than among those on a first-line regimen (3·58, 1·08-11·82; p=0·037). By contrast, the rate of vertical transmission was lower among women who were already on ART at enrolment than among those starting ART at enrolment (0·39, 0·25-0·60; p<0·0001) as well as among women in high-volume clinics than among those in low-volume clinics (0·46 (0·24-0·90; p<0·0097). Provision of ART for life (WHO's option B+ recommendation) has reduced the risk of vertical transmission to less than 2% among pregnant women with HIV in routine care settings in urban Tanzania. There is still a need to improve timely HIV diagnosis and ART uptake, and to optimise follow-up for the prevention of vertical transmission and the uptake of infant HIV testing. Swedish International Development Cooperation Agency.

HIV status disclosure and antiretroviral therapy adherence among children in Masaka region, Uganda

HIV-infected children are now living into adolescence and early adulthood in large numbers due to the availability and increased use of antiretroviral therapy (ART). However, receipt of HIV status disclosure among children remains low. We assessed the association between disclosure of HIV status and adherence to ART among children in the Masaka region of Uganda using multivariable logistic regression with generalised linear models with Poisson log-link function and robust variance in Stata software version 15.1. Data were collected from 524 assenting children aged 12–17 years between March and December 2020. Results show that, although not statistically significant, children who received disclosure of their HIV status reported improved ART adherence compared to children with no disclosure. Out-of-school children with post-primary education and children on first-line ART regimens were significantly more likely to report improved ART in both crude and adjusted analyses. Innovative interventions to promote progressive disclosure of HIV status to children on ART, in school, are needed to improve their ART adherence. There is also a need to evaluate the suitability of current counselling interventions provided to children being switched to second-line ART regimens to delay the need for third-line ART regimens.

Prevalence of HIV-associated Co-infections and Clinical Characteristics among HIV/AIDS Outpatients in the Context of Dolutegravir Roll-out Program in Vietnam

The prevalence of significant HIV-associated co-infections and clinical data of HIV/AIDS outpatients in the context of dolutegravir (DTG) transition are sparsely reported in Vietnam. Treatments of HIV co-infection, including antifungals, anti-tuberculous drugs, and direct-acting antiviral agents for viral hepatitis C, potentially challenge the efficacy of DTG-based therapies in terms of drug-to-drug interactions. We conducted a single-center, cross-sectional study between June and October 2020 in Ho Chi Minh City, Vietnam. HIV-infected outpatients were enrolled in the study when they attended the clinic to receive medical consultations and antiretroviral therapy (ART). Descriptive analyses were performed to describe the data. A total of 406 HIV-infected participants were enrolled in the study. The prevalence of HIV co-infected with chronic viral hepatitis B and C were 9.9% and 10.6%, respectively. Approximately 22.2% of HIV-infected patients had a history of tuberculosis treatment, and roughly 9% of participants experienced invasive fungal infections, mainly cryptococcosis, taralomycosis, and Pneumocystic jirovecii pneumonia. History of sexually transmitted diseases accounted for 40.4%. At the time of DTG transition, roughly 93% of patients were clinically stable, with a median CD4 count of 603 cells/µl. Two-thirds of HIV-infected patients achieved viral suppression (HIV viral load threshold &lt; 20 copies/ml). A total of thirteen (3.2%) patients were ongoingly undertaking protease-inhibitors-based second-line ART regimens. The ART adherence was assessed at 92.1%. The prevalence of HIV-associated co-infections is still high in the context of DTG transition in Vietnam. More effort is needed in order to achieve the UNAIDS 90-90-90 targets.

A comparative study on early treatment outcome and adverse drug reaction profile of two protease inhibitor-based antiretroviral regimens in human immunodeficiency virus patients at a tertiary care teaching hospital, Rajasthan

Introduction: Second-line antiretroviral therapy (ART) regimens are used when patients develop treatment failure from first-line drug regimens. The present study is aimed to compare treatment outcome in terms of clinical, virological, and immunological effectiveness over 1 year of follow-up in human immunodeficiency virus (HIV) patients, switched to various second-line ART regimens and to assess adverse drug reactions (ADRs). Materials and Methods: A longitudinal observational study was conducted at ART center, SMS Hospital, Jaipur, after approval from Institutional Research Review Board. One hundred HIV positive patients, resistant to first line ART, switched to either of the 2 s line ART regimens were followed for 1 year for early treatment outcomes and any ADRs. Results: Out of 97 patients enrolled 65 patients received Tenofovir and 32 patients received Zidovudine (ZDV) along with lamivudine and Atazanavir/ritonavir. There was significant increment in CD4 count from the baseline value (202.51–438.52 cells/mm3) after 12 months of therapy. On comparison, CD4 cell rise was not significantly different between the two groups. However, Plasma viral load suppression was achieved insignificantly more number of patients in ZDV group than in tenofovir group: 31 (96.9%) versus 57 (87.7%), respectively. Opportunistic infections (OI) were seen in 21.5% and 28.1% patients respectively at the time of switching of second-line ART. Out of 59 ADRs reported, nausea, vomiting, diarrhea, hyperbilirubinemia, dyslipidemia, and anemia were most common. Conclusion: Nonadherence, drug resistance, and treatment failure are the major challenges in controlling HIV disease. Our study shows that both the second-line regimens were comparable in improvement in CD4 count and viral load suppression with 1 year success rate of 90.7%.

A comparative study on early treatment outcome and adverse drug reaction profile of two protease inhibitor-based antiretroviral regimens in human immunodeficiency virus patients at a tertiary care teaching hospital, Rajasthan

Introduction: Second-line antiretroviral therapy (ART) regimens are used when patients develop treatment failure from first-line drug regimens. The present study is aimed to compare treatment outcome in terms of clinical, virological, and immunological effectiveness over 1 year of follow-up in human immunodeficiency virus (HIV) patients, switched to various second-line ART regimens and to assess adverse drug reactions (ADRs). Materials and Methods: A longitudinal observational study was conducted at ART center, SMS Hospital, Jaipur, after approval from Institutional Research Review Board. One hundred HIV positive patients, resistant to first line ART, switched to either of the 2 s line ART regimens were followed for 1 year for early treatment outcomes and any ADRs. Results: Out of 97 patients enrolled 65 patients received Tenofovir and 32 patients received Zidovudine (ZDV) along with lamivudine and Atazanavir/ritonavir. There was significant increment in CD4 count from the baseline value (202.51–438.52 cells/mm3) after 12 months of therapy. On comparison, CD4 cell rise was not significantly different between the two groups. However, Plasma viral load suppression was achieved insignificantly more number of patients in ZDV group than in tenofovir group: 31 (96.9%) versus 57 (87.7%), respectively. Opportunistic infections (OI) were seen in 21.5% and 28.1% patients respectively at the time of switching of second-line ART. Out of 59 ADRs reported, nausea, vomiting, diarrhea, hyperbilirubinemia, dyslipidemia, and anemia were most common. Conclusion: Nonadherence, drug resistance, and treatment failure are the major challenges in controlling HIV disease. Our study shows that both the second-line regimens were comparable in improvement in CD4 count and viral load suppression with 1 year success rate of 90.7%.

Determinants of viral load non-suppression among adolescents in Mbale District, Eastern Rural Uganda

BackgroundAdolescents are lagging behind in the “third 95” objective of the Joint United Nations Program on HIV/AIDS requiring 95% of individuals on antiretroviral therapy (ART) to have viral load (VL) suppression. This study aimed to describe factors associated with viral non-suppression among adolescents in Mbale district, Uganda.MethodsWe conducted a retrospective review of routinely collected HIV programme records. Data such as age, education, ART Regimen, ART duration, WHO Clinical stage, comorbidities, etc., were extracted from medical records for the period January 2018 to December 2018. Descriptive analysis was done for continuous variables using means and frequencies to describe study sample characteristics, and to determine the prevalence of outcome variables. We used logistic regression to assess factors associated with VL non-suppression among adolescents.ResultsThe analysis included 567 HIV-infected adolescents, with 300 (52.9%) aged between 13 to 15 years, 335 (59.1%) female, and mean age of 15.6 years (interquartile range [IQR] 13.5–17.8. VL non-suppression was 31.4% (178/567). Male sex (AOR = 1.78, 95% CI 1.06, 2.99; p < 0.01), age 16–19 years (AOR = 1.78, 95% CI 1.06, 2.99; p < 0.05), No formal education (AOR = 3.67, 95% CI 1.48–9.09; p < 0.01), primary education (AOR = 2.23, 95% CI 1.05–2.32; p < 0.01), ART duration of > 12 months to 5 years (AOR = 3.20, 95% CI 1.31–7.82; p < 0.05), ART duration > 5 years (AOR = 3.47, 95% CI 1.39– 8.66; p < 0.01), WHO Clinical Stage II (AOR = 0.48, 95% CI: 0.28, 0.82; p < 0.01), second-line ART regimen (AOR = 2.38, 95% CI 1.53–3.72; p < 0.001) and comorbidities (AOR = 3.28, 95% CI 1.20–9.00; p < 0.05) were significantly associated with viral non-suppression.ConclusionsVL non-suppression among adolescents was almost comparable to the national average. VL non-suppression was associated with being male, age 16–19 years, education level, duration on ART therapy, WHO Clinical Staging II, second-line ART regimen, and presence of comorbidities. Adolescent-friendly strategies to improve VL suppression e.g. peer involvement, VL focal persons to identify and actively follow-up non-suppressed adolescents, patient education on VL suppression and demand creation for ART are needed, especially for newly-initiated adolescents and adolescents on ART for protracted periods, to foster attainment of the UNAIDS 95–95–95 targets.

Factors Associated with Viral Suppression Among Adolescents on Antiretroviral Therapy in Homa Bay County, Kenya: A Retrospective Cross-Sectional Study.

BackgroundDespite the success in initiating adolescents living with HIV on antiretroviral therapy (ART), questions remain about factors affecting viral suppression. In Kenya, only 63% of adolescents (aged 10–19 years) on ART had achieved viral suppression in 2016. We investigated factors associated with viral suppression among adolescents initiated on ART before November 30, 2017 in Homa Bay County, Kenya.MethodsA retrospective cross-sectional analysis of 908 adolescents registered on ART for at least 6 months and with at least one documented viral load in the last 12 months, in six health facilities in Homa Bay County was conducted. Data were extracted from the electronic medical records and exported into an excel spreadsheet. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with viral suppression and adjust for confounding, using Stata 12.0.ResultsOut of all participants, 80% (726) had achieved viral suppression (<1,000 copies of viral RNA/mL of blood at latest viral load count). After adjusting for other covariates, adolescents with good adherence to ART (AOR=2.3, 95% CI=1.38–3.84) and a most recent CD4 count of above 500 cells/mm3 (AOR=1.87, 95% CI=1.13–3.08), were more likely to be virally suppressed. Adolescents on second line ART treatment (AOR=0.45, 95% CI=0.28–0.73) and having inadequate adherence to ART (AOR=0.26, 95% CI=0.11–63) were less likely to be virally suppressed.ConclusionViral suppression for adolescents on ART in this study is significantly higher than the national prevalence in 2016 (80% vs 63%), but it is still below the WHO target of 90%. Enhanced adherence support for adolescents on ART should be implemented to improve long-term adherence. Specific interventions are needed to “rescue” adolescents on second-line ART regimens who may have a history of poor adherence.

Increase in HIV-1-transmitted drug resistance among ART-na\xefve youths at the China-Myanmar border during 2009 ~ 2017

BackgroundHIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART.MethodsFrom 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool.ResultsThe most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013).ConclusionsThe increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

The Comparison of Teen Clubs vs. Standard Care on Treatment Outcomes for Adolescents on Antiretroviral Therapy in Windhoek, Namibia.

Background Adolescents living with HIV (ALHIV) are challenged to adhere to antiretroviral therapy (ART) and achieve and maintain virologic suppression. Group-based adherence support interventions, such as adherence clubs, have been shown to improve long-term adherence in ART patients. The teen club intervention was introduced in 2010 in Namibia to improve treatment outcomes for ALHIV by providing adherence support in a peer-group environment. Adolescents who have completed the full HIV disclosure process can voluntarily join the teen clubs. The current study compared treatment outcomes of ALHIV receiving ART at a specialized paediatric HIV clinic between 1 July 2015 and 30 June 2017 in Windhoek, Namibia. Methods A retrospective cohort analysis was conducted on routine patient data extracted from the electronic Patient Monitoring System, individual Patient Care Booklets, and teen club attendance registers. A sample of 385 adolescents were analysed: 78 in teen clubs and 307 in standard care. Virologic suppression was determined at 6, 12, and 18 months from study start date, and compared by model of care, age, sex, disclosure status, and ART regimen. Comparisons between adolescents in teen clubs and those receiving standard care were performed using the chi-square test, and risk ratios were calculated to analyze differences in ART adherence and virologic suppression. Results The average clinician-measured ART adherence was 89% good, 6% fair, and 5% poor amongst all adolescents, with no difference between teen club members and adolescents in standard care (p = 0.277) at 3 months. Virologic suppression over the 2-year observation period was 87% (68% fully suppressed <40 copies/ml and 19% suppressed between 40–999 copies/ml), with no difference between teen club members and those in standard care. However, there were statistically significant differences in virologic suppression levels between the younger (10–14 years) adolescents and older (15–19 years) adolescents at 6 months (p = 0.015) and at 12 months (p = 0.021) and between adolescents on first-line and second-line ART regimen at 6 months (p = 0.012), 12 months (p = 0.004), and 18 months (p = 0.005). Conclusion The teen club model delivering psychosocial support only did not improve adherence and virologic suppression levels for adolescents in a specialized paediatric ART clinic, neither were they inferior to standard care. Considering the limitations of this study, teen clubs may still hold potential for improving adherence and virologic suppression levels for older adolescents, and more robust research on adherence interventions for adolescents with higher methodological quality is required.

Expanded access to viral load testing and use of second line regimens in Haiti: time trends from 2010\u20132017

BackgroundHaiti initiated the scale-up of HIV viral load (VL) testing in 2015–2016, with plans to achieve 100% coverage for all patients on antiretroviral therapy (ART) for treatment of HIV/AIDS. In the absence of HIV drug susceptibility testing, VL testing is a key tool for monitoring response to ART and optimizing treatment results. This study describes trends in expanded use of VL testing, VL results, and use of second-line ART regimens, and explores the association between VL testing and second-line regimen switching in Haiti from 2010 to 2017.MethodsWe conducted a retrospective cohort study with 66,042 patients drawn from 88 of Haiti’s 160 national ART clinics. Longitudinal data from the iSanté electronic data system was used to analyze the trends of interest. We described patients’ VL testing status in five categories based on up to two most recent VL test results: no test; suppressed; unsuppressed followed by no test; re-suppressed; and confirmed failure. Among those with confirmed failure, we described ART adherence level. Finally, we used Cox proportional hazards regression to estimate the risk of second-line regimen switching by VL testing status, after adjusting for other individual characteristics.ResultsThe number of patients who had tests done increased annually from 11 in 2010 to 18,828 in the first 9 months of 2017, while the number of second-line regimen switches rose from 21 to 279 during this same period. Compared with patients with no VL test, the hazard ratio (HR) for switching to a second-line regimen was 22.2 for patients with confirmed VL failure (95% confidence interval [CI] for HR: 18.8–26.3; p < 0.005) after adjustment for individual characteristics. Among patients with confirmed VL failure, 44.7% had strong adherence, and fewer than 20% of patients switched to a second-line regimen within 365 days of VL failure.ConclusionsHaiti has significantly expanded access to VL testing since 2016. In order to promote optimal patient health outcomes, it is essential for Haiti to continue broadening access to confirmatory VL testing, to expand evidence-based initiatives to promote strong ART adherence, and to embrace timely switching for patients with confirmed ART failure despite strong ART adherence.

Retention in care and virological failure among adult HIV+ patients on second-line ART in Rwanda: a national representative study

BackgroundCurrently, there is limited evidence on the effectiveness of second-line antiretroviral therapy (ART) in sub-Saharan Africa. To address this challenge, outcomes of second-line protease inhibitor (PI) based ART in Rwanda were assessed.MethodsA two-stage cluster sampling design was undertaken. 49 of 340 health facilities linked to the open-source electronic medical record (EMR) system of Rwanda were randomly sampled. Data sampling criteria included adult HIV positive patients with documented change from first to second-line ART regimen. Retention in care and treatment failure (viral load above 1000 copies/mL) were evaluated using multivariable Cox proportional hazards and logistic regression models.ResultsA total of 1688 patients (60% females) initiated second-line ART PI-based regimen by 31st December 2016 with a median follow-up time of 26 months (IQR 24–36). Overall, 92.5% of patients were retained in care; 83% achieved VL ≤ 1000 copies/ml, 2.8% were lost to care and 2.2% died. Defaulting from care was associated with more recent initiation of ART- PI based regimen, CD4 cell count ≤500 cells/mm3 at initiation of second line ART and viral load > 1000 copies/ml at last measurement. Viral failure was associated with younger age, WHO stage III&IV at ART initiation, CD4 cell count ≤500 cells/mm3 at switch, atazanavir based second-line ART and receiving care at a health center compared to hospital settings.ConclusionsA high proportion of patients on second-line ART are doing relatively well in Rwanda and retained in care with low viral failure rates. However, enhanced understandings of adherence and adherence interventions for less healthy individuals are required. Routine viral load measurement and tracing of loss to follow-up is fundamental in resource limited settings, especially among less healthy patients.

Moderate incidence of lost follow-up and risk factors among adult HIV patients on second-line ART regimens in Amhara region hospitals, Ethiopia

Background and Objectives: Loss to follow-up is a common problem of most patients on antiretroviral therapy in Ethiopia. Second-line antiretroviral therapy is the drug that would be used when the first-line therapy fails. Thus this study intends to determine the incidence and risk factors of time to losses to follow up among Human Immunodeficiency Virus (HIV) patients on second line regimens of Antiretroviral Therapy(ART) in Amhara region Hospitals, Ethiopia.&#x0D; Methods: Institutional based retrospective cohort study was conducted in the Amhara region hospitals from February to March 2016. A total of 1246 patient from eight hospitals in Amhara region were selected using simple random sampling method and data were extracted from patient charts. The log rank test was used to assess presence of significant difference in time to losses to follow among levels of categorical variables. Both bi-variiable and multivariable Cox proportional hazards models were used to identify factors that affect the time to losses to follow up. &#x0D; Results: The cumulative incidence of loss to follow up was 5.41% over the entire (eight) years of follow-up. The cumulative incidence rates of death and transfer out were 10.99%,10.02 %, respectively. In multivariable Cox regression analysis, ambulatory functional status (AHR=0.1967, 95% CI: 0.049- 0 .794), male gender (AHR=2.135, 95% CI: 1.053- 4.330), adherence to ART (AHR=0.442, 95% CI: 0.198- 0.989) were significant predictors of time to losses to follow up. The use of 2a, 2e and 2g types of second line regimen reduced the risk of loss to follow up.&#x0D; Interpretations and Conclusions: The incidence of loss to follow up in Amhara region hospitals was low. Loss to folow up was negatively associated with female gender, ambulatory baseline functional status, adherence, &amp; types of second line regimen types. Further research on the effect of types of drug is recommended by acertaining whether the reduction in loss to follow up for patients who took drug types of 2a, 2e, and 2g is associaed with improved or worsened health outcomes by trafcking lost patients closely.

Survival rate and mortality risk factors among TB–HIV co-infected patients at an HIV-specialist hospital in Myanmar: A 12-year retrospective follow-up study

BackgroundMyanmar is listed as one of the countries with the highest burden of tuberculosis and HIV infections (TB–HIV) in the world. However, the survival rate and risk factors for mortality among TB–HIV co-infected patients in the country remain unstudied. Therefore, the purpose of this study was to examine these factors. MethodsA 12-year retrospective follow-up study was conducted among 3598 TB–HIV co-infected patients (2452 male and 1146 female) aged 15 years and above, enrolled on antiretroviral therapy (ART) from July 1, 2005 to December 31, 2016. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Survival rates at the beginning of ART were calculated using the Kaplan–Meier method. ResultsA total of 494 (13.7%) patients died during this period. The survival rate of TB–HIV co-infected patients was 82.0% at 5 years and 58.1% at 10 years. The risk factors for mortality were being bedridden (adjusted hazard ratio (aHR) 2.70, 95% confidence interval (CI) 2.13–3.42), having a low baseline CD4 count (aHR 1.53, 95% CI 1.25–1.87), and being on a second-line ART regimen (aHR 8.12, 95% CI 3.56–18.54). ConclusionsTwo out of five TB–HIV patients died within 10 years after ART initiation. Current HIV prevention and treatment programs should focus more on bedridden patients, those on second-line ART, and those with low baseline CD4 counts.

ART Denial: Results of a Home-Based Study to Validate Self-reported Antiretroviral Use in Rural South Africa.

There is increasing interest in home based testing and treatment of HIV to expand access to treatment in sub-Saharan Africa. Such programs rely on self-reported HIV history and use of antiretroviral therapy (ART). However, the accuracy of self-reported ART use in community settings is not well described. In this study, we compared self-reported ART (SR-ART) use in a home based survey against biological exposure to ART (BE-ART), in a population study of older adults in South Africa. Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa (HAALSI) is a cohort of adults aged 40 +. The baseline home-based interview included self-reported HIV status and ART use. All participants also underwent biological testing for HIV antibodies, viral load and exposure to emtricitabine (FTC) or lamivudine (3TC), which are included in all first-line and second-line ART regimens in the public-sector South African HIV program. We calculated the performance characteristics for SR-ART compared to BE-ART and fit multivariable logistic regression models to identify correlates of invalid SR-ART responses. Of 4560 HAALSI participants with a valid HIV test result available, 1048 (23%) were HIV-positive and 734 [70% of people living with HIV (PLWH)] were biologically validated ART users (BE-ART). The sensitivity of SR-ART use was 64% (95% CI 61-68%) and the specificity was 94% (95% CI 91-96%); the positive predictive value (PPV) was 96% (95% CI 94-98%) and negative predictive value (NPV) was 52% (95% CI 48-56%). We found no sociodemographic predictors of accurate SR-ART use. Over one in three individuals with detectable ART in their blood denied current ART use during a home-based interview. These results demonstrate ongoing stigma related to HIV and its treatment, and have important implications for community health worker programs, clinical programs, and research studies planning community-based ART initiation in the region.

Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa

BackgroundWhile efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes.MethodsRetrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART.ResultsAmong 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively.ConclusionsOur results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods.

Long-term clinical, immunological and virological outcomes of patients on antiretroviral therapy in southern Myanmar.

ObjectiveTo study the long-term clinical, immunological and virological outcomes among people living with HIV on antiretroviral therapy (ART) in Myanmar.MethodsA retrospective analysis of people on ART for >9 years followed by a cross-sectional survey among the patients in this group who remained on ART at the time of the survey. Routinely collected medical data established the baseline clinical and demographic characteristics for adult patients initiating ART between 2004 and 2006. Patients remaining on ART between March-August 2015 were invited to participate in a survey assessing clinical, virological, immunological, and biochemical characteristics.ResultsOf 615 patients included in the retrospective analysis, 35 (6%) were lost-to-follow-up, 9 (1%) were transferred, 153 died (25%) and 418 (68%) remained active in care. Among deaths, 48 (31.4%) occurred within 3 months of ART initiation, and 81 (52.9%) within 12 months, 90.1% (n = 73) of which were initially classified as stage 3/4. Of 385 patients included in the survey, 30 (7.7%) were on second-line ART regimen; 373 (96.8%) had suppressed viral load (<250 copies/ml). The mean CD4 count was 548 cells/ mm3 (SD 234.1) after ≥9 years on treatment regardless of the CD4 group at initiation. Tuberculosis while on ART was diagnosed in 187 (48.5%); 29 (7.6%) had evidence of hepatitis B and 53 (13.9%) of hepatitis C infection.ConclusionsAppropriate immunological and virological outcomes were seen among patients on ART for ≥9 years. However, for the complete initiating cohort, high mortality was observed, especially in the first year on ART. Concerning co-infections, tuberculosis and viral hepatitis were common among this population. Our results demonstrate that good long-term outcomes are possible even for patients with advanced AIDS at ART initiation.

Optimizing resources to reduce costs to determine HIV viral load in limited resources settings

HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.