Detectable VL Research Articles

Brief Report: HIV-Positive and Breastfeeding in High-Income Settings: 5-Year Experience From a Perinatal Center in Germany.

Exclusive breastfeeding is recommended for women living with HIV (WLWH) in low-income-but not in high-income-countries, where milk substitutes are preferred. Some guidelines for high-income countries opted for a shared decision-making process regarding breastfeeding in optimal scenarios with adherence to antiretroviral therapy (cART), suppressed maternal viral load (mVL), and clinical monitoring. Although vertical transmission (VT) risk under cART is estimated below 1% in low-income settings, data from high-income countries are rare. We retrospectively analyzed all 181 live births from WLWH at the LMU Munich university hospital perinatal center in Germany between January 2016 and December 2020. We focused on VT, suppressed mVL and optimal scenario rates, breastfeeding frequency, cART regimens, and infant prophylaxis. All women were counseled according to current guidelines, foremost recommending avoidance of breastfeeding. In the 5-year cohort, no VT was observed. One hundred fifty-one WLWH (83.4%) decided not to breastfeed, even in optimal scenarios. Thrity infants (16.6%) were nursed, of which 25 were within an optimal scenario, whereas in 5 cases, breastfeeding was performed with a detectable VL in pregnancy or the postpartum period. All WLWH were treated with cART at delivery, and 91.7% sustained suppressed mVL. Zidovudine infant prophylaxis was given between 2 and 8 weeks but not necessarily over the whole breastfeeding duration and was declined from 5 breastfeeding WLWH. Although the cohort is too small to assess VT risk through breastfeeding with cART-suppressed mVL, breastfeeding might be an alternative even in high-income countries, but further studies are needed.

Successful virologic outcomes over time among HAART-treated HIV-infected patients

ABSTRACT Few large studies evaluated the effects of time trends on virologic suppression in people living with HIV/AIDS (PLWHA) in China. To address this, An retrospective observational longitudinal study was conducted. We examined annual trends in the rate of virologic suppression, the viral load at the time of virologic suppression, and other determinants of virologic suppression in Zhejiang Province, China in PLWHA between January 2013 and July 2018. Patients who received a treatment regimen for at least 24 weeks were included. Virologic suppression was defined as VL ≤50 copies/mL. Generalized estimating equation logistic regression models were used to adjust for covariates. We included 16,265 patients with 45023 tests. The proportion of patients who experienced an unsuccessful virologic outcome decreased continuously throughout the observation period (18.14% to 6.64%). Time was significantly negatively associated with detectable VL (all ORs <1). Other factors were positively associated with detectable VL, including patients <30 years of age, single, non-adherent to treatment, and with a follow-up CD4 count <200 cells/µL. Patients infected through homosexual transmission and those with a longer ART duration were more likely to reach virologic suppression. We demonstrated outstanding time trend improvements in the virological outcomes of PLWHA in China.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Impact of behavioral and medication treatment for alcohol use disorder on changes in HIV-related outcomes among patients with HIV: A longitudinal analysis

BackgroundFor people with HIV (PWH) and alcohol use disorder (AUD) who initiated behavioral treatment (BAUD) we: 1) describe BAUD intensity and medication (MAUD); and 2) examine whether BAUD and MAUD were associated with changes in HIV-related outcomes (CD4 cell count, HIV-1 viral load [VL], VACS Index score 2.0, and antiretroviral [ARV] adherence) from before to one year after treatment initiation. MethodsWe used Veterans Aging Cohort Study (VACS) data to describe BAUD intensity and MAUD (acamprosate, disulfiram, and naltrexone, gabapentin or topiramate). Linear regression models estimated changes in outcomes and included BAUD, MAUD, age and race/ethnicity. ResultsWe identified 7830 PWH who initiated BAUD from 01/2008−09/2017. Median age was 53, 60% were African-American and 28% white. BAUD intensity groups were: 1) Single Visit - 35%; 2) Minimal - 44% recieved ∼2 visits during first month; 3) Sustained Moderate - 17% recieved ∼8 visits/month initially; and 4) Intensive - 4% started out receiving ∼14−16 visits/month. Only 9% recieved MAUD, the majority of which was gabapentin. Among those with detectable VL: all HIV-related outcomes improved more among those with more intensive BAUD. Among those with undetectable VL: adherence improved more among those with greater BAUD intensity. MAUD was associated with increased CD4 among those with detectable VL and with improved adherence among both groups. ConclusionOf those with >1 BAUD visit, only 21% received at least moderate BAUD and 9% received at least 6 months of MAUD. Increasing AUD treatment intensity may improve HIV-related outcomes, especially among those with detectable VL.

Longitudinal Viral Load Monitoring Using Home-Collected Dried Blood Spot Specimens of MSM Living with HIV: Results from a Feasibility Pilot Study.

Novel viral load monitoring strategies are needed to help individuals maintain an undetectable viral load (UVL). In 2018, U.S. MSM living with HIV with a past detectable VL received a dried blood spot (DBS) kit at baseline and 3-month follow-up and returned specimens to a research laboratory. Of 56 consenting participants, 91% returned specimens at baseline and 77% at 3-month follow-up; 74% who returned two specimens had UVL at both time points. At-home DBS collection and longitudinal VL monitoring is feasible among U.S. MSM with fluctuating viral load. This complementary approach to clinical care could improve viral suppression maintenance.

Nucleoside analog monotherapy for prophylaxis in Hepatitis B liver transplant patients is safe and efficacious.

Combination therapy with HBIG and NAs has reduced HBV recurrence post LT. Despite its efficacy, costs of HBIG remain prohibitive. With high-potency NAs, HBIG's use has been questioned. We aim to evaluate the efficacy and safety of HBIG-free regimens in patients transplanted for HBV-related liver disease. A review of LT patients at the National University Hospital, Singapore from 2001 to 2015 was performed. Patients transplanted for HBV were divided by antiviral treatment received: high- or low-potency NAs, or a combination of HBIG with high-potency NAs. Post-transplant outcomes were reviewed till data censure. Primary outcome was recurrence of HBV viremia post-transplant, while secondary outcomes were HBsAg sero-clearance, graft survival and mortality. Among 58 patients, 51 (88%) had persistent HBV viral suppression. Patients on a high-potency agent had significantly higher viral suppression compared to those on a low-potency agent (97% vs 72%, p = 0.02). This was also seen in patients with VL detectable at transplant (100% vs 50%, p < 0.01). None of the 16 patients with VL detectable at transplant and treated with high-potency agents developed recurrence. 42 patients (72%) achieved persistent HBsAg sero-clearance. Although this was higher in the high-potency NA-only group, it was not statistically significant (p = 0.56). There were no graft failures or mortalities attributed to HBV recurrence. With the use of high-potency agents, HBIG may not be necessary in the treatment of patients transplanted for HBV-related liver disease, even in the presence of detectable VL at time of transplant.

Neighborhood Matters: Impact on Time Living with Detectable Viral Load for New Adult HIV Diagnoses in South Carolina.

We examined the association between neighborhood disadvantages and percent person-time spent with increased transmission risk (VL > 1500 copies/ml) for people living with HIV (PLWH) in South Carolina (SC). The study population included PLWH diagnosedbetween 1/1/2014 and 12/31/2017, with two or more VL tests 6months apart (n = 2076). Proportion of time living with VL > 1500 copies/ml after linkage to care was determined. Neighborhood disadvantage was assessed using thearea deprivation index (ADI). A generalized linear model was fit to generate parameter estimates for time spent with detectable VL. Almost half of PLWH (49.5%) lived with VL > 1500 copies/ml for some time (median days = 46). Young adults and PLWH who injected drugs experienced the highest proportion for time living with detectable VL. Targeted programs are needed to improve VL suppression, reduce new transmissions and decrease disparities in HIV outcomes in all neighborhoods.

Undetectable Hepatitis C Viral Load Is Associated With Improved Outcomes Following Total Joint Arthroplasty

BackgroundPrevious reports establish that infection with hepatitis C virus (HCV) predisposes total joint arthroplasty (TJA) recipients to poor postoperative outcomes. The purpose of the present study is to assess whether variation in HCV VL influences perioperative outcomes following TJA. MethodsA multicenter retrospective review of all patients diagnosed with HCV who underwent primary TJA between January 2005 and April 2018 was conducted. Patients were stratified into 2 cohorts: (1) patients with an undetectable VL (U-VL) and (2) patients with a detectable VL (D-VL). Kaplan-Meier survivorship analysis was calculated with revision TJA as the end point. Subanalysis on the VL profile was done. ResultsA total of 289 TJAs were included (U-VL:118 TJAs; D-VL:171 TJAs). Patients in the D-VL cohort had longer operative times (133.9 vs 109.2 minutes), higher intraoperative blood loss (298.4 vs 219.5 mL), longer inpatient hospital stays (4.0 vs 2.9 days), more postoperative infections (11.7% vs 4.2%), and an increased risk for revision TJA (12.9% vs 5.1%). Kaplan-Meier demonstrated that the U-VL cohort trended toward better survivorship (P = .17). On subanalysis of low and high VL, no difference in outcomes was appreciated. ConclusionTJA recipients with a detectable HCV VL have longer operative times, experience more intraoperative blood loss, have longer hospital length of stay, and are more likely to experience infection and require revision TJA. The blood loss, hospital length of stay, and revision rate findings should be interpreted with caution, however, as there are confounding factors. Our findings suggest that HCV VL is a modifiable risk factor that, can reduce the risk of infection and revision surgery. Additionally, serum HCV VL was not correlated with outcomes.

Criminal Justice System Involvement as a Risk Factor for Detectable Plasma HIV Viral Load in People Who Use Illicit Drugs: A Longitudinal Cohort Study.

Among HIV-positive people who use illicit drugs (PWUD) in our setting, repeated periods of incarceration adversely affect ART adherence in a dose-dependent manner. However, the impact of non-custodial criminal justice involvement on HIV-related outcomes has not been previously investigated. Data were obtained from a longitudinal cohort of HIV-positive PWUD in a setting of universal no-cost ART and complete dispensation records. Multivariate generalized estimating equations were used to calculate the longitudinal odds of having a detectable HIV VL (VL) associated with custodial and non-custodial CJS exposure. Between 2005 and 2014, 716 HIV-positive ART-exposed PWUD were recruited. In multivariate analysis, both custodial [Adjusted odds ratio (AOR) 0.61, 95% CI 0.45-0.82] and noncustodial (AOR 0.78, 95% CI 0.62-0.99) involvement in the criminal justice system was associated with detectable HIV VL. Among HIV-positive PWUD, both custodial and non-custodial criminal justice involvement is associated with worse HIV treatment outcomes. Our findings highlight the need for increased ART adherence support across the full spectrum of the criminal justice system.

Depression preceding Parkinson's disease: Risk factor or early symptom?

Previous reports establish that infection with hepatitis C virus (HCV) predisposes total joint arthroplasty (TJA) recipients to poor postoperative outcomes. The purpose of the present study is to assess whether variation in HCV VL influences perioperative outcomes following TJA.A multicenter retrospective review of all patients diagnosed with HCV who underwent primary TJA between January 2005 and April 2018 was conducted. Patients were stratified into 2 cohorts: (1) patients with an undetectable VL (U-VL) and (2) patients with a detectable VL (D-VL). Kaplan-Meier survivorship analysis was calculated with revision TJA as the end point. Subanalysis on the VL profile was done.A total of 289 TJAs were included (U-VL:118 TJAs; D-VL:171 TJAs). Patients in the D-VL cohort had longer operative times (133.9 vs 109.2 minutes), higher intraoperative blood loss (298.4 vs 219.5 mL), longer inpatient hospital stays (4.0 vs 2.9 days), more postoperative infections (11.7% vs 4.2%), and an increased risk for revision TJA (12.9% vs 5.1%). Kaplan-Meier demonstrated that the U-VL cohort trended toward better survivorship (P = .17). On subanalysis of low and high VL, no difference in outcomes was appreciated.TJA recipients with a detectable HCV VL have longer operative times, experience more intraoperative blood loss, have longer hospital length of stay, and are more likely to experience infection and require revision TJA. The blood loss, hospital length of stay, and revision rate findings should be interpreted with caution, however, as there are confounding factors. Our findings suggest that HCV VL is a modifiable risk factor that, can reduce the risk of infection and revision surgery. Additionally, serum HCV VL was not correlated with outcomes.

HIV-RNA decay in paired blood and semen samples of subjects receiving their first dolutegravir-based ART regimen

Background and objectivesWe aimed to investigate to what extent a first-line DTG-based ART regimen reduces HIV-RNA in semen compared to plasma. Study designIn this prospective, observational study, ART-naïve, HIV-infected males starting their first ART regimen with DTG plus TDF/FTC or ABC/3TC were enrolled. Paired blood (BP) and seminal plasma (SP) samples were collected at baseline (T0) and at week-2/4/12/24 after ART initiation. Sexually transmitted infections (STI) were ruled out before enrolment. ResultsMedian baseline HIV-RNA levels were lower in SP compared to BP (657 versus 38.200 copies/ml, p < 0.001), three subjects had undetectable semen HIV-RNA. After 12 weeks of treatment, HIV-RNA was below the quantification limit in both BP and SP of 11 pts (61.1%). Discordant results were obtained in 6 subjects (33.3%), showing quantifiable HIV-RNA in blood only (2 cases) and in semen only (4 cases). Finally, one subject had a positive HIV-RNA in SP/BP. At W24, only in 2/16 subjects (12.5%) HIV-RNA was detectable in semen, while in the others it was negative on SP/BP. No concurrent STI was found in subjects with detectable VL in semen. ConclusionsDTG demonstrated effectiveness in reducing VL with different kinetics in blood and semen, despite seminal viral suppression after 6 months of ART was not obtained in the totality of subjects.

Patients with core antibody positive and surface antigen negative Hepatitis B (anti-HBc+, HBsAg−) on anti-TNF therapy have a low rate of reactivation

Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation of Hepatitis B virus (HBV) is associated with immunosuppressive agents and biologics such as anti-TNF. There are limited data and differing guidelines for patients with negative hepatitis B surface antigen (HBsAg−) but positive antibody to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation in a single-center retrospective cohort study of 120 HBsAg−, anti-HBc+ patients on anti-TNF, totaling 346.6 patient years. One patient (0.8%) who had a detectable VL (<20 IU) prior to starting anti-TNF had reactivation of HBV with sero-conversion to positive HBsAg. Three patients (2.5%) had undetectable HBV VL prior to anti-TNF and developed detectable VL while on anti-TNF. In conclusion, there was a low rate of HBV reactivation or development of detectable HBV DNA in HBsAg−, anti-HBc+ patients on anti-TNF.

Nasal Nitric Oxide Levels in HIV Infection: A Cross-Sectional Study.

Introduction Low levels of nasal NO have been associated with increased propensity to rhinosinusitis and respiratory tract infections. Our objective was to describe nasal NO levels in HIV-infected individuals versus healthy controls and determine possible risk factors for reduced nasal NO levels. Materials and Methods HIV-infected individuals and healthy controls were recruited. Participants underwent nasal NO testing by standardized methods using a CLD88 chemiluminescence analyzer and completed the Sinonasal Outcome Test-20 (SNOT-20) on symptoms of rhinosinusitis. Results Participants included 41 HIV-infected individuals with suppressed VL on antiretroviral therapy (ART group), 5 HIV-infected individuals with detectable VL off ART (viremic group), and 12 healthy controls (HC group). Mean nasal NO level was 253 (±77) nL/min in the ART group, 213 (±48) nL/min in the viremic group, and 289 (±68) nL/min in the HC group (p = 0.133; ANOVA). There was no correlation between nasal NO level and VL in viremic individuals (r = −0.200; p = 0.747). Differences were observed in mean total points on the SNOT-20 which were 19 (±16)/100, 18 (±26)/100, and 4 (±4)/100 in the ART, viremic, and HC groups, respectively (p = 0.013; ANOVA). Conclusion Healthy individuals, HIV patients on ART, and viremic individuals off ART display similar nasal NO levels. However, rhinosinusitis symptoms remain prominent despite ART-treatment.

Association between public injecting and drug-related harm among HIV-positive people who use injection drugs in a Canadian setting: A longitudinal analysis

Backgroundand Aims Injecting illicit drugs in public settings has been linked to a higher risk of a range of drug-related harms, including overdose and HIV infection. However, the factors associated with public injecting among HIV-positive individuals have not been previously explored. We investigated the links between public drug injecting, drug-related harm, and HIV treatment measures among a cohort of HIV-positive persons who inject drugs (PWID) in a Canadian setting. MethodsWe used data from a prospective cohort of HIV-positive PWID recruited from community settings in Vancouver, Canada, linked to comprehensive clinical monitoring data in the context of an ongoing Treatment-as-Prevention (TasP) initiative to examine harms associated with public injecting. We used generalized linear mixed-effects analyses to identify longitudinal factors associated with self-reported public drug injection. ResultsBetween 2005 and 2014, 626 HIV-seropositive PWID were recruited, of whom 213 (34%) reported public injection in the preceding 180days. In a longitudinal multivariable model, public injection was positively associated with daily heroin injection (Adjusted Odds Ratio [AOR]=2.63), incarceration (AOR=1.78), and detectable plasma HIV-1 RNA viral load (VL, AOR=1.42). ConclusionsPublic injecting was linked to numerous drug-related harms among HIV-seropositive PWID in this setting. Given its link with detectable VL, an important marker of poor HIV treatment outcomes, our findings support prioritizing individuals engaged in public injecting with harm reduction strategies as well as clinical and social supports as a part of TasP-based efforts to prevent HIV-related morbidity and mortality, and HIV transmission.

Interferon-γ-Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings.

Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints. HIV-1-infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ-inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10-based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction. From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80-.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%-96.7%) and 59.9% specificity (95% CI, 52.0%-67.4%), values confirmed in the validation set. IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings.

Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death.

ObjectiveTo investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management.DesignNested case-control study within the EuroSIDA cohort.MethodsCases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling.ResultsThe study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, p<0.001). Baseline tropism was not associated with the risk of clinical progression or death. CD4+T-cell slopes did not differ within or between tropism groups.ConclusionsThe predictive role of plasma tropism determined using 454 sequencing in the context of people receiving cART with detectable VL is not helpful to identify subjects at higher risk for clinical progression to AIDS or death.

Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study.

Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission. A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL > 400 copies/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL > 40 copies/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL. Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1β (adjPRR = 2.14; 95% confidence interval (CI) = 1.02-4.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28-3.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15-5.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67-3.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15-3.03) were associated with penile HIV shedding at the subsequent visit. Men with 2-4 (adjPRR = 2.36; 95% CI = 1.08-5.14) and 5-7 (adjPRR = 3.00; 95% CI = 1.28-7.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with ≤ 1 detectable cytokine. The total number of detectable cytokines was also associated with a higher penile log10 HIV VL at the subsequent visit among HIV shedders. Pro-inflammatory cytokine production had a dose-dependent and temporal association with penile HIV shedding, suggesting that genital immune activation may increase the risk of sexual HIV transmission by driving local HIV replication.

Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study.

IntroductionSome antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort.MethodsA discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda.ResultsAmong 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not.ConclusionsDiscordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes.

Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.

As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P < .001) or PI-based (7.59; 3.02-19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P < .001), and suboptimal adherence (3.05; 1.71-5.42; P = .025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.

Factors associated with lack of viral suppression at delivery among highly active antiretroviral therapy-naive women with HIV: a cohort study.

A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health. To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy. Multicenter observational study. (ClinicalTrial.gov: NCT00028145). 67 U.S. AIDS clinical research sites. Pregnant women with HIV who initiated HAART during pregnancy. Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery. Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P=0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P<0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P=0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P=0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P=0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P=0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery. Data on many covariates were incomplete because women entered the study at varying times during pregnancy. A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence. U.S. Department of Health and Human Services.