Detectable HIV RNA Research Articles

A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy.

Depot medroxyprogesterone acetate (DMPA) use among HIV-1-infected women may increase transmission by increasing plasma and genital HIV-1 RNA shedding. We investigated associations between DMPA use and HIV-1 RNA in plasma and cervical secretions. One hundred two women initiated antiretroviral therapy, contributing 925 follow-up visits over a median of 34 months. Compared with visits with no hormonal contraception exposure, DMPA exposure did not increase detection of plasma (adjusted odds ratio: 0.81, 95% confidence interval: 0.47 to 1.39) or cervical HIV-1 RNA (adjusted odds ratio: 1.41, 95% confidence interval: 0.54 to 3.67). Our results suggest that DMPA is unlikely to increase infectivity in HIV-positive women who are adherent to effective antiretroviral therapy.

Probability of a false-negative HIV antibody test result during the window period: a tool for pre- and post-test counselling.

Failure to understand the risk of false-negative HIV test results during the window period results in anxiety. Patients typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false-negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-generation HIV tests and provides the probability of a false-negative result for various days post-exposure. Data were extracted from published seroconversion panels. A 10-day eclipse period was used to estimate days from infection to first detection of HIV RNA. Median (interquartile range) days to seroconversion were calculated and probabilities of a false-negative result at various time periods post-exposure are reported. The median (interquartile range) window period for third-generation tests was 22 days (19-25) and 18 days (16-24) for fourth-generation tests. The probability of a false-negative result is 0.01 at 80 days' post-exposure for third-generation tests and at 42 days for fourth-generation tests. The table of probabilities of falsely-negative HIV test results may be useful during pre- and post-test HIV counselling to inform co-decision making regarding the ideal time to test for HIV.

Sensibilidad del equipo Cobas AmpliScreen™ HIV-1 Test, v1.5, para la detección de HIV-1

The introduction of nucleic acid amplification techniques (NAT) in blood banks was intended to reduce the residual risk of transfusion-transmitted infections. Co-circulation of a great diversity of HIV-1 variants in Argentina portrays the need to assess the sensitivity of serological and molecular assays available for their detection. In this study, we evaluated the sensitivity of the COBAS AmpliScreen™ HIV-1 Test, version 1.5 (Roche) for the detection of HIV-1 RNA in plasma samples of infected individuals from Argentina. The results of this study reveal that this technique has high sensitivity for the detection of HIV-1 RNA under assay conditions: using mini-pool testing, pools ≥ 50 RNA copies per ml achieved ≥ 92 % sensitivity, whereas in the standard procedure, samples ≥ 207 RNA copies/ml achieved 100 % sensitivity. Moreover, the COBAS AmpliScreen™ HIV-1 Test, version 1.5 (Roche) is suitable for detecting prevailing HIV-1 variants.

Is There a Higher Risk of CNS Adverse Events for PI Monotherapy Versus Triple Therapy? A Review of Results From Randomized Clinical Trials

Background: Protease inhibitor (PI) monotherapy for treatment could avoid the adverse events, drug resistance, and additional costs associated with other antiretrovirals that are normally used, particularly the nucleoside analogues. PI monotherapy has mainly been compared with standard triple therapy in randomized clinical trials of patients who have HIV RNA suppression at screening and no history of virological failure. Methods: This review included 11 randomized clinical trials of darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy versus triple therapy in 1,267 patients with HIV RNA suppression at baseline who were studied between 48 and 144 weeks. Results: There was no clear difference in the risk of central nervous system (CNS) adverse events between PI monotherapy (either DRV/r or LPV/r) and standard triple drug treatment. There were 2 clinical trials – MONOI (DRV/r) and MOST (LPV/r) – that showed CNS symptoms and detectable HIV RNA levels in the cerebrospinal fluid in a small number of individuals taking PI monotherapy. Conclusions: There was no consistent evidence from the randomized trials currently available for an additional risk of HIV CNS disease during monotherapy with either LPV/r or DRV/r versus standard triple drug therapy. However, the information on CNS adverse events has not been reported using standardized definitions in the studies. In addition, few randomized studies included detailed analysis of neurocognitive function or detection of HIV RNA in the cerebrospinal fluid.

Rate, Predictors, and Consequences of Late Antenatal Booking in a National Cohort Study of Pregnant Women With HIV in Italy

Objective: To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. Methods: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. Results: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). Conclusions: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.

Association between symptomatic vulvovaginal candidiasis and HIV RNA levels in plasma and genital secretions among women on HAART

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART). Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients’ medical records.Results. Plasma HIV RNA was detected in 42 of 60 (70%) patients on HAART. The mean duration (± standard deviation) on HAART for these patients was 4.2 (±1.6) months v. 10.7 (±1.4) months for the remaining 18 patients (p&lt;0.0001). Of the 42 women with detectable plasma HIV RNA, 12 (28.6%) had detectable genital HIV RNA. Plasma HIV RNA levels ranged from 2.5 (±0.8) to 4.1 (±0.8) log10 copies/ml. Genital HIV RNA levels ranged from 1.4 to 2.5 (±1.1) log10 copies/ml. The adjusted odds ratios of plasma HIV RNA levels increased for patients &lt;35 years (p=0.039) and in those with VVC (p=0.008). Detectability of HIV in genital secretions was significantly increased in patients with a plasma HIV load ≥10 000 copies/ml (p=0.032) and genital absolute counts of neutrophils &gt;10 cells/5 high microscopic fields (p=0.007). Conclusion. Given that the majority of women had recently initiated HAART (allowing a high rate of detectable plasma HIV RNA), there was insufficient evidence to conclude that VVC was predictive of high plasma HIV RNA levels. It is more likely that this cohort of immunosuppressed women were prone to develop VVC. Plasma HIV loads and local genital inflammation were predictors of genital HIV detectability.

Association between symptomatic vulvovaginal candidiasis and HIV RNA levels in plasma and genital secretions among women on HAART

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART). Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients' medical records. Results. Plasma HIV RNA was detected in 42 of 60 (70%) patients on HAART. The mean duration (± standard deviation) on HAART for these patients was 4.2 (±1.6) months v. 10.7 (±1.4) months for the remaining 18 patients (p 10 cells/5 high microscopic fields (p=0.007). Conclusion. Given that the majority of women had recently initiated HAART (allowing a high rate of detectable plasma HIV RNA), there was insufficient evidence to conclude that VVC was predictive of high plasma HIV RNA levels. It is more likely that this cohort of immunosuppressed women were prone to develop VVC. Plasma HIV loads and local genital inflammation were predictors of genital HIV detectability.

Issues in cytomegalovirus chronic infection in HIV patients

The prevalence of cytomegalovirus (CMV) in HIV infected patients is 90%. Both CMV and HIV are involved in the pathogenesis of metabolic and cardiovascular diseases. The study retrospectively evaluated the correlation of CMV infection with lipodystrophy (LD) and hypertension (HTA) in HIV patients who have been beneficiaries of medical care in Galați, during 2013. The evolution of anthropometric parameters, CDC-HIV categories, the immunity by LyCD4, the category of detectable or undetectable HIV-RNA, the categories high/low for values of cholesterol, triglycerides, glucose, fibrinogen and for serological CMV-IgG (ELISA), were collected from the records of 165 patients. CMV-IgG titers were converted in high or low dichotomous variables, referring to the quartile (Q) 3. Statistical analysis (XL-Stat) evaluated the correlations between groups, with χ2 test for dichotomous variables and Student’s t test for continuous variables. The characteristics of patients are: median age 25 years [20;50]; men sex 53.7%; rural area 50.3%; low literacy (<4 years) 25%; smokers 58%; co-infection with HBV 28.5%; median length of HIV diagnosis 12 years; AIDS category 74%; current antiretroviral treatment 95%, with average 2 [0;8] previous combinations; median nadir LyCD4=144/cmm, median current LyCD4=507/cmm, undetectable HIV-RNA (<400 copies/mL) 69%. The prevalence of positive CMV-IgG is 87% and 25.5% of the values are over Q3. Hypertension was found in 9.7% and LD in 48% of patients, specifying 36% atrophy (LA), 6% hypertrophy (LH) and 6% mixed lipodystrophy (ML). High values of CMV-IgG were associated with severe immunosuppression of nadir LyCD4 (p=0.002), high fibrinogen level (p<0.001), HTA (p=0.032) and ML pattern (p<0.001). There was no correlation of CMV-IgG with LA, LH, HIV-RNA, cholesterol, triglycerides and glucose. The levels of CMV-IgG should be monitored in HIV patients as a risk factor for hypertension and mixed lipodystrophy in order to allow early interventions for management of these co-morbidities.

Application of Real Time loop mediated isothermal amplification (RT LAMP) as a point of care assay using dried blood spots for rapid detection of HIV infection

Background Early and rapid diagnosis of HIV is essential to reduce the transmission and to start Anti Retroviral Therapy. The increasingly sophisticated molecular methods for diagnosing acute HIV infection have a direct impact on patient management as they have been developed to overcome the limitations of serological assays. Development of a further methodology, which is technologically simple and equally sensitive, accessible and affordable, is essential to detect the very few copies of viral genome during acute HIV infection. Hence in the present study a Real Time Loop Mediated Isothermal Amplification (RT LAMP) assay on Dried Blood Spots (DBS) for the detection of HIV RNA was developed for an early and specific diagnosis of HIV.

Discordances with HIV-1 RNA quantitative determinations by three commercial assays in Pointe Noire, Republic of Congo

Accurate HIV-1 RNA quantitation is required to support the scale up of antiretroviral therapy in African countries. Extreme HIV-1 genetic variability in Africa may affect the ability of commercially available assays to detect and quantify HIV-1 RNA accurately. The aim of this study was to compare three real-time PCR assays for quantitation of plasma HIV-1 RNA levels in patients from the Republic of Congo, an area with highly diversified HIV-1 subtypes and recombinants.The Abbott RealTime HIV-1, BioMérieux HIV-1 EasyQ test 1.2 and Cobas AmpliPrep/Cobas TaqMan HIV-1 1.0 were compared for quantitation of HIV-1 RNA in 37 HIV-1 seropositive pregnant women enrolled in the Kento-Mwana project for prevention of mother-to-child transmission in Pointe-Noire, Republic of Congo. The sample panel included a variety of HIV-1 subtypes with as many as 21 (56.8%) putative unique recombinant forms.Qualitative detection of HIV-1 RNA was concordant by all three assays in 33/37 (89.2%) samples. Of the remaining 4 (10.8%) samples, all were positive by Roche, three by Abbott and none by BioMérieux. Differences exceeding 1Log in positive samples were found in 4/31 (12.9%), 10/31 (32.3%) and 5/31 (16.1%) cases between Abbott and BioMérieux, Roche and BioMérieux, and Abbott and Roche, respectively.In this sample panel representative of highly polymorphic HIV-1 in Congo, the agreement among the three assays was moderate in terms of HIV-1 RNA detectability and rather inconsistent in terms of quantitation.

Predictors of virologic response in persons who start antiretroviral therapy during recent HIV infection

Despite evidence supporting antiretroviral therapy (ART) in recent HIV infection, little is known about factors that are associated with successful ART. We assessed demographic, virologic, and immunologic parameters to identify predictors of virologic response. A 24-week observational study of ART on persons enrolled within 6 months of their estimated date of infection (EDI) evaluated baseline demographics and the collection of blood and gut specimens. Flow cytometry analyses of blood and gut lymphocytes allowed characterization of CD4 and CD8 T cells at study entry and end. Additional assessments included soluble CD14 (sCD14), lipopolysaccharide, CD4 T-cell counts, and HIV RNA levels. Twenty-nine participants initiated ART, and 17 achieved undetectable HIV RNA by study end. A longer time from EDI to ART, older age, higher sCD14, lower proportions of central memory CD4 T cells, and higher proportions of activated CD8 T cells were associated with detectable viremia. Multivariable logistic regression found only older age and elevated sCD14 were independently associated with persistent viremia. Additionally, we observed that ART in recent infection did not result in discernible recovery of CD4 T cells in the gut. In persons who started ART within 3-33 weeks from EDI, age and microbial translocation were associated with detectable HIV RNA. As observed in other cohorts, ART in recent infection did not improve proportions of total CD4 T cells in gut-associated lymphoid tissue (GALT). This lends support to further evaluate the use of more potent ART or regimens that protect the GALT in recent HIV infection.

The impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected, opioid-dependent patients

BackgroundOpioid dependence is a major risk factor for HIV infection, however, the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected opioid-dependent patients is unknown. MethodsWe conducted a longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day needle-sharing and non-condom use. We assessed trends over the 12 months using the Cochran–Armitage trend test. Using generalized estimating equations, after multiple imputation, we determined factors independently associated with needle-sharing and non-condom use, including time-updated variables. We then conducted a mediation analysis to determine whether substance use explained the relationship between time since treatment initiation and needle-sharing. ResultsNeedle-sharing decreased from baseline to the fourth quarter following initiation of buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23% vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a detectable HIV-1 RNA viral load. Patients who were homeless and used heroin, cocaine/amphetamines or marijuana were more likely to report needle-sharing. Heroin use fully mediated the relationship between time since treatment initiation and needle-sharing. Women, patients who identified as being gay/lesbian/bisexual, those married or living with a partner and who reported heroin or alcohol use were more likely to report non-condom use. Older patients were less likely to report non-condom use. ConclusionsWhile buprenorphine/naloxone is associated with decreased needle-sharing among HIV-infected opioid-dependent patients, sexual risk behaviors persist regardless of viral load. Targeted interventions to address HIV risk behaviors among HIV-infected opioid-dependent populations receiving buprenorphine/naloxone are needed.

Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting 'Rwanda') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (Ptrend=0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding.

CP-023 Effect of treatment complexity on medicines adherence and incidence of blips in HIV/HCV co-infected patients

BackgroundAnti-HCV treatment may add significant complexity to antiretroviral treatment (ART). The complexity of the medicines regimen could be a risk factor for non-adherence or increasing incidence of blips.PurposeTo determine if...

Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women

ObjectiveSelenium supplementation for women infected with HIV may increase genital shedding of HIV-1, however, to our knowledge, no studies have examined the effect on viral shedding in breast milk. The aim of this study was to determine the effect of selenium supplementation on HIV-1 RNA detection in breast milk of HIV-infected women. MethodsHIV-infected pregnant women enrolled at 12 to 27 wk gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 μg as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4 to 9 wk postpartum. All participants received high-dose multivitamins containing vitamin B complex, C, and E as standard of care. ResultsThe proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) compared with those in the placebo group (27.5%) among the total cohort (N = 420), but results were borderline statistically significant (relative risk [RR], 1.32; 95% confidence interval [CI], 1.00–1.76; P = 0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) compared with placebo group (27.5%) among women who did not receive highly active antiretroviral therapy (HAART; RR, 1.37; 95% CI, 1.03–1.82; P = 0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR, 2.24; 95% CI, 1.30–3.86; P < 0.01), but not multiparous women (RR, 1.14; 95% CI, 0.81–1.59; P = 0.54) (P-value for interaction = 0.02). Too few women received HAART in this study (n = 12) to establish the effect of selenium supplementation. ConclusionsSelenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before administering selenium-containing supplements.

Gender differences in HIV infection: Is there a problem? Analysis from the SCOLTA cohorts

ObjectivesEvaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project. MethodsThe SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc). ResultsTwo thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm3 and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio=0.39, 95% confidence interval 0.18–0.88; P=0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently. ConclusionsIn these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence.

The importance of HIV RNA detection below 50 copies per mL in HIV-positive patients on antiretroviral therapy: an observational study

BackgroundSuppression of plasma HIV viral load to less than 50 copies per mL is associated with durable clinical and immunological benefits and is the recommended goal of antiretroviral therapy (ART). Currently available viral load assays can detect HIV RNA below this threshold but the importance of low-level detection is unclear. We aimed to determine whether HIV RNA detection below 50 copies per mL is associated with an increased risk of virological rebound in ART-treated patients. Methods1247 HIV-positive patients on ART with viral load less than 50 copies per mL at a single arbitrary timepoint as measured by RealTime PCR (Abbott, Maidenhead, UK) were stratified by the clinically unreported viral load into three groups: 40–49 copies per mL (RNA40–49), less than 40 copies per mL but not quantifiable (RNA+), and not detected (RNA−). Virological outcomes over the following 12 months were analysed. Time to viral load rebound according to baseline viral load category was assessed and the factors associated with rebound were identified in a Cox proportional hazards model incorporating baseline viral load, clinical and demographic data, and adherence levels. FindingsOver 12 months of follow-up the proportion of patients experiencing viral load rebound of more than 50 copies per ml in the RNA40–49, RNA+, and RNA–groups were 34·2% (82/240), 11·3% (57/507), and 4% (20/500), respectively. For viral rebound of more than 400 copies per mL the proportions were 13% (31/240), 3·8% (19/507), and 1·2% (6/500), respectively. After multivariate adjustment, the hazard ratio for rebound of more than 400 copies per mL was 6·91 (95% CI 2·90–16·47, p<0·0001) for baseline RNA40–49 and 2·88 (1·24–6·69, p<0·0001) for baseline RNA+. Baseline viral load category predicted rebound independently of adherence levels. InterpretationIn ART-treated HIV-positive patients, detection of viral load between 40 and 49 copies per mL and less than 40 copies per mL (as measured by RealTime PCR) is associated with an increased risk of virological failure. The currently recommended goal of ART of 50 copies per mL might be suboptimal and might need to be revised to a lower cut-off. FundingRoyal Free Hospital NHS Trust, European AIDS Treatment Network.

Cervicovaginal HIV-1 Shedding in Women Taking Antiretroviral Therapy in Burkina Faso

Background:Antiretroviral therapy (ART) reduces transmission of HIV-1. However, genital HIV-1 can be detected in patients on ART. We analyzed factors associated with genital HIV-1 shedding among high-risk women on ART in Burkina Faso.Methods:Plasma viral load (PVL) and enriched cervicovaginal lavage HIV-1 RNA were measured every 3–6 months for up to 8 years. Random-effects logistic and linear regression models were used to analyze associations of frequency and quantity of genital HIV-1 RNA with behavioral and biological factors, adjusting for within-woman correlation. The lower limit of detection of HIV-1 RNA in plasma and eCVL samples was 300 copies per milliliter.Results:One hundred and eighty-eight participants initiated ART from 2004 to 2011. PVL was detectable in 16% (171/1050) of visits, in 52% (90/174) of women. Cervicovaginal HIV-1 RNA was detectable in 16% (128/798) of visits with undetectable plasma HIV-1 RNA in 45% (77/170) of women. After adjusting for PVL, detectable cervicovaginal HIV-1 RNA was independently associated with abnormal vaginal discharge and use of nevirapine or zidovudine vs. efavirenz and stavudine, respectively; longer time on ART and hormonal contraception were not associated with increased shedding. The presence of bacterial vaginosis, herpes simplex virus-2 DNA, and the use of nevirapine vs efavirenz were independently associated with an increased quantity of cervicovaginal HIV-1 RNA.Conclusions:Certain ART regimens, abnormal vaginal discharge, bacterial vaginosis, and genital herpes simplex virus-2 are associated with HIV-1 cervicovaginal shedding or quantity in women on ART after adjusting for PVL. This may reduce the effectiveness of ART as prevention in high-risk populations.

Factors associated with high transmission risk and detectable plasma HIV RNA in HIV-infected MSM on ART

Summary HIV transmission risk is increased during antiretroviral therapy (ART) use if individuals are not virologically suppressed and engage in high risk transmission behaviour. Baseline data of HIV-infected men who have sex with men (MSM) with recent history of risky behaviour on ART for ≥3 months (n = 139) were evaluated to assess predictors of detectable viraemia and HIV transmission risk-taking behaviour. Twenty-four subjects had viral load (VL) >75 copies/mL and 12 had VL >1000 copies/mL. In multivariable regression analyses, subjects with VL >75 copies/mL were more likely to be Black (OR = 4.48, p = 0.007), have lower CD4 cell counts (OR = 0.727, p = 0.005) and have used methamphetamines in the last month (OR = 6.64, p = 0.019). Subjects with VL >1000 copies/mL were more likely to have lower CD4 cell counts (OR = 0.494, p = 0.004), report <90% adherence (OR = 7.94; p = 0.046) and have used methamphetamines in the last month (OR = 10.01, p = 0.034). Subjects with VL >75 copies/mL with the greatest transmission risk behaviour (n = 14) were more likely to be Black (OR = 8.00, p = 0.006), have lower CD4 cell counts (OR = 0.657, p = 0.009) and have used methamphetamines in the last month (OR = 5.20, p = 0.042). High risk HIV transmission behaviour with viraemia occurred in 10% of the cohort. Future efforts to reduce HIV transmission among MSM on ART will require combined interventions that target risk-taking behaviours and substance use.

HIV-1 Specific Antibody Titers and Neutralization among Chronically Infected Patients on Long-Term Suppressive Antiretroviral Therapy (ART): A Cross-Sectional Study

The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1JR-FL) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1JR-FL neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.