CD4 Cell Count Decline Research Articles

Bridged Treatment Comparisons: an Illustrative Application in HIV Treatment.

Comparisons of treatments, interventions, or exposures are of central interest in epidemiology, but direct comparisons are not always possible due to practical or ethical reasons. Here, we detail a fusion approach to compare treatments across studies. The motivating example entails comparing the risk of the composite outcome of death, AIDS, or greater than a 50% CD4 cell count decline in people with HIV when assigned triple versus mono antiretroviral therapy, using data from the AIDS Clinical Trial Group (ACTG) 175 (mono versus dual therapy) and ACTG 320 (dual versus triple therapy). We review a set of identification assumptions and estimate the risk difference using an inverse probability weighting estimator that leverages the shared trial arms (dual therapy). A fusion diagnostic based on comparing the shared arms is proposed that may indicate violation of the identification assumptions. Application of the data fusion estimator and diagnostic to the ACTG trials indicates triple therapy results in a reduction in risk compared to monotherapy in individuals with baseline CD4 counts between 50 and 300 cells/mm3. Bridged treatment comparisons address questions that none of the constituent data sources could address alone, but valid fusion-based inference requires careful consideration of the underlying assumptions.

Impact of HIV-1 CRF55_01B infection on the evolution of CD4 count and plasma HIV RNA load in men who have sex with men prior to antiretroviral therapy

BackgroundCRF55_01B is a newly identified HIV-1 circulating recombinant form originated from MSM in China. However, its impact on the disease progression and transmission risk has not been investigated. This study aimed to determine the impact of CRF55_01B infection on viral dynamics and immunological status so as to provide scientific evidence for further control and prevention effort on CRF55_01B. Linear mixed effect models were applied to evaluate CD4 cell count decline and viral load increase by subtype.ResultsOf the 3418 blood samples, 1446 (42.3%) were CRF07_BC, 1169 (34.2%) CRF01_AE, 467 (13.7%) CRF55_01B, 249 (7.3%) type B, and 87 (2.5%) other subtypes (CRF_08BC, CRF_01B, C). CRF55_01B had become the third predominant strain since 2012 in Shenzhen, China. CRF55_01B-infected MSM showed lower median of CD4 count than CRF07_BC-infected MSM (349.5 [IQR, 250.2–474.8] vs. 370.0 [IQR, 278.0–501.0], P < 0.05). CRF55_01B infection was associated with slower loss of CD4 count than CRF01_AE (13.6 vs. 23.3 [cells/µl]¹/²/year, P < 0.05)among MSM with initial CD4 count of 200–350 cells/µl. On the other hand, those infected with CRF55_01B showed higher median plasma HIV RNA load (5.4 [IQR, 5.0–5.9]) than both CRF01_AE (5.3 [IQR, 4.8–5.7], P < 0.05) and CRF07_BC (5.0 log10 [IQR, 4.5–5.5], P < 0.001) at the initiation of antiretroviral therapy. Furthermore, the annual increasing rate of viral load for CRF55_01B infection was significantly higher than that of CRF07_BC (2.0 vs. 0.7 log10 copies/ml/year, P < 0.01).ConclusionsThe relatively lower CD4 count and faster increase of plasma HIV RNA load of CRF55_01B-infected MSM without antiretroviral therapy suggest that CRF55_01B may lead to longer asymptomatic phase and higher risk of HIV transmission. Strengthened surveillance, tailored prevention strategies and interventions, and in-depth research focusing on CRF55_01B are urgently needed to forestall potential epidemic.

Statistical Joint Modeling for Predicting the Association of CD4 Measurement and Time to Death of People Living with HIV Who Enrolled in ART, Southwest Ethiopia.

BackgroundIn much epidemiological HIV research, patients are often followed over a period of time to predict their survival on the basis of repeatedly measured CD4 status. To predict survival, statistical models of the association between mortality and longitudinal CD4 measurement have been conducted widely using time-varying Cox models. However, in the presence of repeated measure, this approach leads to biased estimates. In view of the limitation of time-varying Cox models, in the present study, we considered joint modeling to predict the association of longitudinal CD4 measurement and time to death among patients initiated on ART.MethodsA retrospective cohort study was employed for five years from 2009 to 2014 on a randomly selected 358 samples. Data were collected from patients’ ART and pre-ART follow-up registration book, database and other clinical records. Data were analyzed using joint latent class modeling of repeated CD4 measurement and time-to-event (HIV death).ResultsWe have studied a total of 358 HIV-positive patients. The median and interquartile ranges of the age of patients were 30.31 years and 13.82, respectively. Males constitute the larger proportion, 51.68%. The square root of CD4 count has declined on average over time. This has been indicated with the negative sign of the coefficient for the time effect. The deterioration of health of individuals is severe in class 1, it has been observed with a worse decline in CD4 cell counts over time in this class than other classes (β= −0.488). Women had a larger risk rate than men (β=−2.475, p-value=0.013). Besides, the CD4 counts measurement of patients has been revealed to decrease as age increases (β= −0.016, p=0.008).ConclusionThe finding indicated that the square root CD4 cell measurement dropped over time in the three classes. This clearly suggested deterioration in the health of individuals. Women were found to have a higher hazard rate than men.

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in People Living with HIV-1

Background: The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with HIV-1 (PLWH) are unknown. We thus aimed to assess the immunogenicity and safety of this vaccine in PLWH.Methods: In this prospective open study, we enrolled 143 PLWH, aged ³18 years, who attended our clinic. Patients who had recovered from COVID-19 were excluded. SARS-CoV-2 receptor binding domain (RBD) IgG and neutralizing antibodies were measured and compared to those in a cohort of vaccinated health care workers (HCWs). Adverse events, viral load and CD4 cell counts were monitored.Findings: At a median of 15 (IQR 14-19) days following the first dose of the BNT162b2 vaccine and 18 (IQR 14-21) days after the second dose, anti-RBD IgG was positive in 66/128 (51%) and 139/141 (98%) PLWH, respectively. Among the HCWs, 235/399 (59%) and 269/272 (99%) developed anti-RBD IgG at a median of 14 (IQR 14-14) and 26 (IQR 24-27) days after first and second doses, respectively. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus (psSARS-2) in 97% and 98% of PLWH and HCW, respectively. Vaccination was associated with adverse events in 60% of PLWH, mainly pain at the injection site, fatigue, and headache. AIDS-related adverse events were not reported. HIV viral load increased in 3/143 (2%) patients from 3 to 633.8 (95% CI 588–683) cells/mm 3 (PInterpretation: This study on BNT162b2 vaccination in PLWH revealed a high antibody response without detrimental effect on viral load. A small decline in CD4 cell count was noted, but it was not accompanied by clinical deterioration. This study thus provides support for the immunization of PLWH against COVID-19 with the BNT162b2 mRNA Covid-19 vaccine.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: Written informed consent was obtained from all participants and the study protocol and informed consent were approved by the Institutional review board of Sheba Medical Center.

HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer.

HIV-positive women have higher human papillomavirus (HPV) prevalence and cervical cancer incidence than HIV-negative women, partly because of HIV's modifying effect on HPV pathogenesis. We synthesized the literature on the impact of HIV on HPV natural history. Systematic review and meta-analysis. We searched the literature for studies evaluating HPV acquisition and persistence or precancer progression by HIV status. Data on HPV natural history by HIV status, CD4 cell counts, viral load, and antiretroviral therapy (ART) were summarized using fixed effect models. Overall, 38 of 1845 abstracts identified met inclusion criteria. HIV-positive women had higher HPV acquisition [relative risk (RRpooled) 2.64, 95% confidence interval (CI) 2.04-3.42] and lower HPV clearance (hazard ratiopooled 0.72, 95% CI 0.62-0.84) than HIV-negative women. HPV acquisition was higher with declining CD4 cell count and was lower in those virally suppressed on ART. HIV was associated with higher incidence of low-grade squamous intraepithelial lesions (LSIL; RRpooled 3.73, 95% CI 2.62-5.32) and high-grade squamous intraepithelial lesions (HSIL; hazard ratiopooled 1.32, 95% CI 1.10-1.58), largely because of increased HPV persistence. ART lowered progression from normal cytology to LSIL (hazard ratiopooled 0.65, 95% CI 0.52-0.82), but not HSIL. Cervical cancer incidence was associated with HIV positivity (RR 4.1, 95% CI 2.3-6.6), but not with ART. HIV-positive women have higher risk of acquiring HPV, with risk inversely associated with CD4 cell count. ART lowered HPV acquisition, increased clearance, and reduced precancer progression, likely via immune reconstitution. Although some of our results are limited by small number of studies, our study can inform screening guidelines and mathematical modeling for cervical cancer prevention.

Alcohol Use and HIV Disease Progression in an Antiretroviral Naive Cohort.

Alcohol use has been shown to accelerate disease progression in experimental studies of simian immunodeficiency virus in macaques, but the results in observational studies of HIV have been conflicting. We conducted a prospective cohort study of the impact of unhealthy alcohol use on CD4 cell count among HIV-infected persons in southwestern Uganda not yet eligible for antiretroviral treatment (ART). Unhealthy alcohol consumption was 3-month Alcohol Use Disorders Identification Test-Consumption positive (≥3 for women, ≥4 for men) and/or phosphatidylethanol (PEth-an alcohol biomarker) ≥50 ng/mL, modeled as a time-dependent variable in a linear mixed effects model of CD4 count. At baseline, 43% of the 446 participants were drinking at unhealthy levels and the median CD4 cell count was 550 cells/mm (interquartile range 416-685). The estimated CD4 cell count decline per year was -14.5 cells/mm (95% confidence interval: -38.6 to 9.5) for unhealthy drinking vs. -24.0 cells/mm (95% confidence interval: -43.6 to -4.5) for refraining from unhealthy drinking, with no significant difference in decline by unhealthy alcohol use (P value 0.54), adjusting for age, sex, religion, time since HIV diagnosis, and HIV viral load. Additional analyses exploring alternative alcohol measures, participant subgroups, and time-dependent confounding yielded similar findings. Unhealthy alcohol use had no apparent impact on the short-term rate of CD4 count decline among HIV-infected ART naive individuals in Uganda, using biological markers to augment self-report and examining disease progression before ART initiation to avoid unmeasured confounding because of misclassification of ART adherence.

Aiming for 90-90-90 - the importance of understanding the risk factors for HIV exposure and advanced HIV infection in migrant populations and other groups who do not report male-to-male sex.

Victorian public health surveillance data were used to classify migrants as having likely acquired HIV before or after arrival to Australia using a CD4 cell count decline method to estimate date of infection. Place of exposure for Australian-born people was estimated based on self-report. Factors associated with place of HIV acquisition, advanced infection and newly acquired infection were explored among migrants and among Australian-born people. Between July 1996 and June 2014, there were 821 new non-MSM HIV diagnoses. Most (58%) were migrants, and of these, half (54%) were estimated to have acquired HIV before migration. Among Australian-born people, 27% reported exposure likely occurring abroad; the majority of these were men who reported exposure in South-East Asia. Advanced infection was common in migrants (45%) and Australian-born people (35%). Among migrants, birth in South-East Asia was associated with increased odds of advanced infection. These results highlight the potential vulnerability of migrants after arrival in Australia, especially those from South-East Asia and Sub-Saharan Africa, and that of Australian-born men travelling to these regions. Public health practice must be strengthened to meet prevention needs of these populations in line with Australian policy.

CD4 count and tuberculosis risk in HIV-positive adults not on ART: a systematic review and meta-analysis.

BackgroundCD4 cell count in adults with human immunodeficiency virus (HIV) infection (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite widespread use in models informing resource allocation, this relationship has not been systematically reviewed.MethodsWe systematically searched MEDLINE, Aidsinfo, Cochrane review database and Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell count in cohorts of HIV-positive adults (age ≥15 years) not on ART (PROSPERO protocol no: CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect to CD4 cell count decrement.ResultsA total of 1,555 distinct records were identified from which 164 full text articles were obtained. Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 measurements, and not reporting TB incidence by ART status. The seven studies included reported on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of four years. Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 (95% credible interval: 1.16–1.88)-fold increase in TB incidence per 100 cells per mm3 decrease in CD4 cell count.DiscussionOur analysis confirms previous estimates of exponential increase in TB incidence with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to reduce TB risk in PLHIV.

High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009-2014.

BackgroundDrug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy.ObjectivesThis study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy.Materials and methodsData from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model.ResultsFrom 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/μL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p<0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10–2.63; p=0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47–6.59; p<0.001). There was no association between HIV-1 subtype, viral load, and resistance.ConclusionThis study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.

Early evolution of human leucocyte antigen-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C-infected women.

HIV-1 escape from cytotoxic T-lymphocytes results in the accumulation of human leucocyte antigen (HLA)-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of cytotoxic T-lymphocyte escape in a cohort followed from infection for 5 years. Viral loads and CD4 cell counts were monitored in 78 subtype C-infected individuals from onset of infection until CD4 cell count decline to less than 350 cells/μl or 5 years postinfection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months postinfection were mapped. HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4 decline to less than 350 cells/μl (P = 0.05). Escape mutations in variable Gag proteins (p17 and p7p6) had a greater impact on disease progression than escape in more conserved regions (p24) (P = 0.03). The association between HLA-associated escape mutations and CD4 decline was independent of protective HLA allele (B57, B58 : 01 and B81) expression. The high frequency of escape contributed to rapid disease progression in this cohort. Although HLA-adaption in both conserved and variable Gag domains in the first year of infection was detrimental to long-term clinical outcome, escape in variable domains had greater impact.

Non-R5-tropic HIV-1 in subtype A1 and D infections were associated with lower pretherapy CD4+ cell count but not with PI/(N)NRTI therapy outcomes in Mbarara, Uganda.

Previous studies suggest that infection with non-R5-tropic subtype B HIV-1, compared with R5, is associated with a more rapid decline in CD4 cell count, but does not affect PI/(N)NRTI therapy outcome. Here, we explored clinical correlates associated with viral tropism in subtype A1 and D infections. HIV-1 subtype A1 (n = 196) and D (n = 143) pretherapy plasma samples and up to 7.5 years of posttherapy virologic and CD4 data were collected from a cross-sectional cohort in Mbarara, Uganda. Tropism and subtype were inferred using env V3 (geno2pheno) and gp41 (RIP) Sanger sequences. For each subtype, R5 infection was compared with non-R5 in terms of: pretherapy viral load and CD4 cell count (Mann-Whitney tests), and therapy outcomes, including time to virologic suppression, postsuppression virologic rebound, CD4 decline and CD4 recovery (log-rank tests). A 94% of all patients in this study achieved virologic suppression within median 3 months posttherapy. In both subtypes, non-R5 infection was associated with lower pretherapy CD4 cell count (non-R5 vs. R5; A: median 57 vs. 147 cells/μl P = 0.005; D: 80 vs. 128 cells/μl P = 0.006). Multivariable linear regression confirmed that tropism, not subtype nor the interaction between subtype and tropism, was a significant predictor of pretherapy CD4 cell count (P < 0.0001). None of pretherapy viral load, time to virologic suppression, virologic rebound, CD4 decline nor CD4 recovery was significantly different (all P > 0.09). Regardless of HIV-1 subtype or tropism, the majority of patients in this Ugandan cohort responded to therapy, even though non-R5 infection was associated with lower pretherapy CD4 cell count.

Factors associated with HIV RNA viral loads in ART-naïve patients: implications for treatment as prevention in concentrated epidemics

BackgroundLimited data are available on factors associated with HIV-RNA viral load (VL) among antiretroviral treatment (ART)-naïve key populations in concentrated epidemics. MethodsWe conducted a cross-sectional survey of 1211 adult ART-naïve patients at 19 HIV clinics in Ho Chi Minh City (HCMC), Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, hepatitis serology and HIV VL. Correlation between CD4 cell count and VL was assessed across all participants. In 904 participants not meeting Vietnam criteria for ART (CD4 cell count >350 cells/mm3, WHO clinical stage 1 or 2 and not pregnant), multivariate analyses were conducted to assess factors associated with HIV VL. ResultsPre-ART patients had a median age of 31 years and 54% were male. Median CD4 cell count was 533 cells/mm3. Median HIV VL was 17,378 copies/mL; 60% had VL greater than 10,000 copies/mL and 16% had VL above 100,000 copies/mL. Although declining CD4 cell count was correlated with rising VL across all CD4 cell counts, correlation of VL with CD4 cell counts between 351 and 500 cell/mm3 was not significant. On multivariate linear regression, higher HIV VL was independently associated with male sex, men who have sex with men (MSM), CD4 cell count 351–500, HIV diagnosis within the previous 6 months, and hepatitis B (HBV). Lower HIV VL was independently associated with hepatitis C (HCV). ConclusionsThe majority of HIV patients who were not eligible for ART in HCMC in 2014 had HIV VL greater than 10,000 copies/mL. These data support expanded eligibility of ART to all HIV patients with the goal of treatment as prevention. This study is also among the first to demonstrate that MSM had a higher VL than women and heterosexual men and highlights the need for improved outreach and linkages to HIV care for this high-risk group.

Immune recovery among HIV-infected patients in northwestern Tanzania after 2 years of anti-retroviral therapy use: a retrospective cohort study

Background: The use of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) is associated with significant and sustained decrease in the viral RNA levels that allows the immune system to recover. The extent of this immune recovery depends on the baseline CD4 count. Evidence on the extent of immune recovery in patients with advanced HIV from resource limited settings is scarce. The objective of this study was to determine immune recovery in a cohort of HIV infected outpatients after using ART for a period of 2 years. Methods: This retrospective cohort study was conducted in an outpatient HIV clinic at Bugando Medical Centre in northwestern Tanzania. CD4+ T-cell counts for HIV-positive adults at the time of enrolment were measured and retrospectively followed up during ART eligibility screening process prior to initiation of antiretroviral (ARV) drugs. We then compared the CD4+ T-cell counts at baseline and that during the enrolment. Results: A total of 238 patients files were screened for enrolment. Of the 238 patients, 171 (71.8%) fulfilled the criteria and were enrolled for the study. The lack of participation was due to death 17 (7.1%), lost to follow-up 32 (13.4%) and refusal 18 (9.5%). Of the 171 patients, the median CD4 count at the time of ART initiation was 153 cells/µl [Interquartile range (IQR): 78 – 199], 164 (95.9%) had increased their CD4 cells count, with 74.3% having an increase of more than 150 cells/µl. Only 8 (4.7%) patients had a decline of CD4 cell count. The median CD4 cells count after a 2-year follow up was significantly higher (396 [IQR: 295 – 567]) than at baseline (153 [IQR: 78 – 199]) cells/ul; p-value &lt;0.0001). Conclusion: The CD4 cells count increased significantly after a follow up period of 2 years after ART use in this cohort. Early diagnosis and ART initiation could therefore improve outcomes in HIV-infected patients in resource limited settings.

Vitamin D Deficiency May Be Associated with a More Rapid Decline in CD4 Cell Count to

Low vitamin D status is associated with both increased disease progression and mortality in people with HIV receiving antiretroviral therapy (ART). However, data are lacking on effects of vitamin status on disease progression and CD4 cell count in people with HIV not receiving ART. We therefore evaluated effects of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) on the decline in CD4 cell count in people with HIV not receiving ART. A retrospective cohort study including people with HIV not receiving ART and with an HIV viral load of >400 copies/mL. A proportional hazards model was fitted to evaluate the effect of vitamin D status on the time to decline in CD4 cell count (<350 cells/µL), adjusted for nadir CD4 cell count, time since HIV diagnosis, previous ART use and HIVviral load. 224 participants fulfilled the inclusion criteria and were followed for a median of 11 months (range or IQR). At baseline, 42% had vitamin D deficiency and the median (interquartile range) CD4 cell count was 502 (355, 662) cells/µL. HIV-infected individuals with vitamin D deficiency had an increased risk of CD4 decline to <350 cells/µL [Hazard ratio (HR) 2.15 (95% CI 1.05, 4.38, p=0.04)]. Vitamin D deficiency was independently associated with an increased time to decline in CD4 cell count to <350 cells/µL, but not with a change in CD4 overall in people with HIV not receiving ART.

Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period.

The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/μL and 15% (six of 41) a CD4 count < 200 cells/μL at their return. A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.

Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial.

Objective:To examine the effect of selenium supplementation on CD4+ T-cell counts, viral suppression, and time to antiretroviral therapy (ART) initiation in ART-naive HIV-infected patients in Rwanda.Methods:A multicenter, double-blinded, placebo-controlled, randomized clinical trial was conducted. Eligible patients were HIV-infected adults (≥21 years) who had a CD4+ cell count between 400 and 650 cells/μl (ART eligibility was ≤350 cells/μl throughout the trial), and were willing to practice barrier methods of birth control. Patients were randomized to receive once-daily 200 μg selenium tablets or identical placebo. They were followed for 24 months with assessments every 6 months. Declines in CD4+ cell counts were modeled using linear regressions with generalized estimating equations and effect modification, and the composite outcome (ART eligible or ART initiation) using Cox proportional-hazards regression, both conducted with intention to treat.Results:Of the 300 participants, 149 received selenium, 202 (67%) were women, and median age was 33.5 years. The rate of CD4+ depletion was reduced by 43.8% [95% confidence interval (CI) 7.8–79.8% decrease] in the treatment arm – from mean 3.97 cells/μl per month to mean 2.23 cells/μl per month. We observed 96 composite outcome events – 45 (47%) in the treatment arm. We found no treatment effect for the composite outcome (hazard ratio 1.00, 95% CI 0.66–1.54) or viral suppression (odds ratio 1.18, 95% CI 0.71–1.94). The trial was underpowered for the composite outcome due to a lower-than-anticipated event rate. Adverse events were comparable throughout.Conclusions:This randomized clinical trial demonstrated that 24-month selenium supplementation significantly reduces the rate of CD4+ cell count decline among ART-naive patients.

Aining Granule Stabilizes the Decline of CD4 Cell Count in HAART-Receiving HIV/AIDS Patients Having Virologic Failure

Objective: To explore the pattern of slow-down of CD4 T cell depletion by Aining granule administration. Method: The data of prospective, randomized, placebo-controlled and double blinded clinical trials enrolling one hundred HIV/AIDS individuals, randomized into two groups, one with 50 cases administered with Aining granule plus the combination of d4T, ddI and NVP, and the other received with placebo plus the combination of d4T, ddI and NVP for observing in a duration of 11 months in were re-analyzed to observe the course of different CD T cells over the treatment period. Results: Only the patients in the Aining granule treatment group (7, vs 0 in the control group, deviation exceeding 2 sigmas) had stable CD4 T cell count over the treatment course. Conclusion: Our results provided insights into molecular investigation of the relation between the active ingredients of Aining granule, DNA replication and HIV-induced CD4 T cell death.

Impact of Symptomatic HIV- Related Neurocognitive Disorders in Survival of HIV- Infected Individuals: A Systematic Review and Meta-Analyses

Background: HIV- related symptomatic neurocognitive disorders (SNCD) negatively influence the survival of affected patients. We conducted this meta-analysis to provide pooled estimates of mortality risk attributable to SNCD. Methods: MEDLINE, Google scholar, Cochrane library PsycINFO and EMBASE were the data bases thoroughly searched up to April 2014. Two parallel meta-analyses were performed to derive hazard ratio (HR) and relative risk (RR) of mortality from 7 and 6 studies respectively. The level statistical heterogeneity in the included studies was assessed using I-squared (I2) statistic while metaregression and subgroup analyses mainly explored clinical and methodological heterogeneity. Other assessments were analyses for publication bias, small study effect, single study effect and study quality. Results: Thirteen studies with satisfactory quality met the inclusion criteria. A total of 84 421 HIV+ individuals across 21 countries from Europe and America were involved. Subjects with SNCD have more than twice risk of death compared to subjects without SNCD: HR=2.1, 95% confidence interval (CI)=1.52-2.58; RR=2.46, 95% CI=1.63-3.69. The estimated HR translates in to 72% probability of subjects with SNCD dying earlier than subjects without SNCD. Risk of mortality is associated with declining CD4 cell count (p=0.038) and neurocognitive impairment in psychomotor and memory domains. In subgroup analyses, there was no significant difference in mortality risk with respect to HAART utilization, type of SNCD and availability of demographically adjusted normative scores. Despite limiting generalizability of findings to sub-Saharan Africa, inclusion of studies conducted in developed countries reduces confounding and increases the accuracy of defining pooled estimates. Conclusion: HIV- related SNCD negatively influence survival in affected patients. Routine care of these patients should include neurocognitive screening preferably with a battery assessing domains that are predictive of mortality such as psychomotor and memory domains.

The effects of HIV-1 subtype and ethnicity on the rate of CD4 cell count decline in patients naive to antiretroviral therapy: a Canadian-European collaborative retrospective cohort study.

Ethnic differences have the potential to confound associations between HIV-1 subtype and immunologic progression. We compared declines in CD4 cell counts during untreated infection for the most prevalent HIV-1 subtypes, focusing on distinguishing between the effects of viral subtype and ethnicity. We combined data from 4 European and 6 Canadian cohorts, selecting adults in the stable chronic phase of untreated HIV infection. We estimated the change in square root CD4 cell count over time for subtypes and ethnicities using mixed models, adjusting for covariates selected for their potential effect on initial CD4 cell count or its decline. Data from 9772 patients were analyzed, contributing 79175 measurements of CD4 cell count and 24157 person-years of follow-up. Overall, there were no appreciable differences in CD4 cell count decline for viral subtypes A, CRF01_AE, CRF02_AG, C and G compared with viral subtype B; whereas the decline in CD4 cell count in patients of African ancestry was considerably slower than in patients of other ethnicity. When ethnic groups were studied separately, there was evidence for slower declines in CD4 cell count in viral subtypes C, and possibly A and G, compared with viral subtype B in patients of African ancestry but not among patients of other ethnicities, suggesting an interaction between subtype and ethnicity. Ethnicity is a major determinant of CD4 cell count decline; viral subtype differences may have existed but were small compared with the effect of ethnicity and were most apparent in patients of African ancestry. In developing countries, slower CD4 cell count declines among individuals of African descent may translate to a longer asymptomatic phase and increase the opportunity for HIV transmission.

HIV-1 superinfection is associated with an accelerated viral load increase but has a limited impact on disease progression.

HIV-1 superinfection occurs frequently in high-risk populations, but its clinical consequences remain poorly characterized. We undertook this study to determine the impact of HIV-1 superinfection on disease progression. In the largest prospective cohort study of superinfection to date, we compared measures of HIV-1 progression in women who acquired superinfection with those who did not. Clinical and laboratory data were collected at quarterly intervals. Linear mixed effects models were used to compare postacute viral load and CD4 T-cell counts over time in singly infected and superinfected women. Cox proportional hazards analysis was used to determine the effect of superinfection on time to clinical progression [CD4 cell count <200 cells/μl, antiretroviral therapy (ART) initiation or death]. Among 144 women, 21 of whom acquired superinfection during follow-up, the rate of viral load increase was higher in superinfected than in singly infected women (P = 0.0008). In adjusted analysis, superinfected women had lower baseline viral load before superinfection (P = 0.05) and a trend for increased viral load at superinfection acquisition (P = 0.09). We also observed a borderline association of superinfection with accelerated CD4 cell count decline (P = 0.06). However, there was no significant difference in time to clinical progression events. These data suggest that superinfection is associated with accelerated progression in laboratory measures of HIV-1 disease, but has a limited impact on the occurrence of clinical events. Our observation that superinfected individuals have lower baseline viral load prior to superinfection suggests that there may be host or viral determinants of susceptibility to superinfection.