Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Background

Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.

Methods and Findings

A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS.282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively.The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.

Conclusions

Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00055120","term_id":"NCT00055120"}}NCT00055120     

High Levels of Adherence and Viral Suppression in a Nationally Representative Sample of HIV-Infected Adults on Antiretroviral Therapy for 6, 12 and 18 Months in Rwanda

Background

Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART) in Africa.

Methods

We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL) measurements. Multivariable logistic regression examined predictors of non-perfect (<100%) 30-day adherence and detectable VL (>40 copies/ml).

Results

Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months); younger age; reporting severe (vs. no or few) side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL); alcohol use; and attending sites which initiated ART services in 2003–2004 and 2005 (vs. 2006–2007); sites with ≥600 (vs. <600 patients) on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL.

Conclusions

High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.     

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

Objective

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART).

Methods

Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART.

Results

After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months.

Interpretation

We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.     

Susceptibility to Transmitting HIV in Patients Initiating Antiretroviral Therapy in Rural District Hospitals in Cameroon (Stratall ANRS 12110/ESTHER Trial)

Objectives

Using cohort data nested in a randomized trial conducted in Cameroon, this study aimed to investigate time trends and predictors of the susceptibility to transmitting HIV during the first 24 months of treatment.

Methods

The outcome, susceptibility to transmitting HIV, was defined as reporting inconsistent condom use and experiencing incomplete virological suppression. Mixed logistic regressions were performed to identify predictors of this outcome among 250 patients reporting to have had sexual relationships either with HIV-negative or unknown HIV status partner(s).

Results

Despite an initial decrease from 76% at M0 to 50% at M6, the rate of inconsistent condom use significantly increased from M12 (59%) to M24 (66%) (p = 0.017). However, the proportion of patients susceptible to transmitting HIV significantly decreased over follow-up from 76% at M0, to 50% at M6, 31% at M12 and 27% at M24 (p<0.001). After controlling for age, gender and intervention group, we found that perceiving healthcare staff’s readiness to listen as poor (adjusted odds ratios (AOR) [95% Confidence Interval (CI)] = 1.87 [1.01–3.46]), reporting to have sexual relationships more than once per week (AOR [95%CI] = 2.52 [1.29–4.93]), having more than one sexual partner (AOR [95%CI] = 2.53 [1.21–5.30]) and desiring a/another child (AOR [95%CI] = 2.07 [1.10–3.87]) were all associated with a higher risk of being susceptible to transmitting HIV. Conversely, time since ART initiation (AOR [95%CI] = 0.66 [0.53–0.83] for an extra 6 months and ART adherence (AOR [95%CI] = 0.33 [0.15–0.72]) were significantly associated with a lower risk of being susceptible to transmitting HIV.

Conclusions

The decrease observed in the susceptibility to transmitting HIV suggests that fear of behavioural disinhibition should not be a barrier to universal access to ART. However, developing adequate preventive interventions matching patients’ expectations -like the desire to have children- and strengthening healthcare staff’s counselling skills are urgently needed to maximize the impact of ART in slowing the HIV epidemic.     

Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco

Background

At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco''s community viral load (CVL) as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004–2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART) coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections.

Methodology/Principal Findings

We used San Francisco''s HIV/AIDS surveillance system to examine the trends in CVL. Mean CVL was calculated as the mean of the most recent viral load of all reported HIV-positive individuals in a particular community. Total CVL was defined as the sum of the most recent viral loads of all HIV-positive individuals in a particular community. We used Poisson models with robust standard errors to assess the relationships between the mean and total CVL and the primary outcome: annual numbers of newly diagnosed HIV cases. Both mean and total CVL decreased from 2004–2008 and were accompanied by decreases in new HIV diagnoses from 798 (2004) to 434 (2008). The mean (p = 0.003) and total CVL (p = 0.002) were significantly associated with new HIV cases from 2004–2008.

Conclusions/Significance

Reductions in CVL are associated with decreased HIV infections. Results suggest that wide-scale ART could reduce HIV transmission at the population level. Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.     

Mortality among Methadone Maintenance Clients in China: A Six-Year Cohort Study

Objective

To assess the overall mortality of methadone maintenance treatment (MMT) clients in China and its associated factors.

Methods

A total of 1,511 MMT clients, all of whom enrolled in China''s first eight MMT clinics between March and December 2004, were included in this cohort study and followed for approximately six years, until June 2010. Mortality and its predictors were examined using Cox proportional hazards regression models.

Results

A total of 154 deaths were observed within 5,391 person-years (PY) of follow-up for an all-cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The all-cause mortality rate of clients engaged in MMT for one year or less was roughly three times that of clients who stayed in MMT for four years or more (14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV-positive subjects had approximately two times higher mortality rate than those receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding variables, we found that being male (HR = 1.63, CI: 1.03–2.57, p = 0.0355) and being HIV-positive (HR = 5.16, CI: 3.70–7.10, p<0.0001) were both associated with higher risk of death whereas increased durations of methadone treatment were associated with a lower risk of death (HR = 0.26, CI: 0.18–0.38, p<0.0001 for two to three years, HR = 0.08, CI: 0.05–0.14, p<0.0001 for four or more years).

Conclusion

Overall mortality was high among MMT clients in China. Specific interventions aimed at decreasing mortality among MMT clients are needed. Our study supports the need for keeping client at MMT longer and for expanding ART coverage and suggests the potential benefits of integrated MMT and ART services for drug users in China.     

Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

Background

In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.

Methods

HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).

Results

In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures).

Conclusions

In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.     

Multidimensional Patient-Reported Problems within Two Weeks of HIV Diagnosis in East Africa: A Multicentre Observational Study

Objectives

We aimed to determine for the first time the prevalence and severity of multidimensional problems in a population newly diagnosed with HIV at outpatient clinics in Africa.

Methods

Recently diagnosed patients (within previous 14 days) were consecutively recruited at 11 HIV clinics in Kenya and Uganda. Participants completed a validated questionnaire, the African Palliative Outcome Scale (POS), with three underpinning factors. Ordinal logistic regression was used to evaluate risk factors for prevalence and severity of physical, psychological, interpersonal and existential problems.

Results

There were 438 participants (62% female, 30% with restricted physical function). The most prevalent problems were lack of help and advice (47% reported none in the previous 3 days) and difficulty sharing feelings. Patients with limited physical function reported more physical/psychological (OR = 3.22) and existential problems (OR = 1.54) but fewer interpersonal problems (OR = 0.50). All outcomes were independent of CD4 count or ART eligibility.

Conclusions

Patients at all disease stages report widespread and burdensome multidimensional problems at HIV diagnosis. Newly diagnosed patients should receive assessment and care for these problems. Effective management of problems at diagnosis may help to remove barriers to retention in care.     

The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Objective

To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment.

Design

We conducted a systematic literature review and meta-analysis. Studies published from 1996 through February 15, 2013, were identified by searching electronic resources (Pubmed and Embase) and conference books, manual searches of references, and expert consultation. Pooled estimates for the outcome of interest were acquired using random effects meta-analysis.

Subjects

The study population included individuals receiving ART before or during TB treatment.

Main Outcome Measures

Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the proportion of individuals dying during TB treatment and, if mortality in HIV-positive people not on ART was also reported, (ii) the relative risk of death during TB treatment by ART status.

Results

Twenty-one studies were included in the systematic review. Random effects pooled meta-analysis estimated the CFR between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those receiving ART had a reduction in mortality during TB treatment of between 44% and 71% (RR = 0.42, 95%CI: 0.29–0.56).

Conclusion

Starting ART before or during TB therapy reduces the risk of death during TB treatment by around three-fifths in clinical settings. National programmes should continue to expand coverage of ART for HIV positive in order to control the dual epidemic.     

Antiretroviral treatment for HIV in rural Uganda: two-year treatment outcomes of a prospective health centre/community-based and hospital-based cohort

Background

In sub-Saharan Africa, a shortage of trained health professionals and limited geographical access to health facilities present major barriers to the expansion of antiretroviral therapy (ART). We tested the utility of a health centre (HC)/community-based approach in the provision of ART to persons living with HIV in a rural area in western Uganda.

Methods

The HIV treatment outcomes of the HC/community-based ART program were evaluated and compared with those of an ART program at a best-practice regional hospital. The HC/community-based cohort comprised 185 treatment-naïve patients enrolled in 2006. The hospital cohort comprised of 200 patients enrolled in the same time period. The HC/community-based program involved weekly home visits to patients by community volunteers who were trained to deliver antiretroviral drugs to monitor and support adherence to treatment, and to identify and report adverse reactions and other clinical symptoms. Treatment supporters in the homes also had the responsibility to remind patients to take their drugs regularly. ART treatment outcomes were measured by HIV-1 RNA viral load (VL) after two years of treatment. Adherence was determined through weekly pill counts.

Results

Successful ART treatment outcomes in the HC/community-based cohort were equivalent to those in the hospital-based cohort after two years of treatment in on-treatment analysis (VL≤400 copies/mL, 93.0% vs. 87.3%, p = 0.12), and in intention-to-treat analysis (VL≤400 copies/mL, 64.9% and 62.0%, p = 0.560). In multivariate analysis patients in the HC/community-based cohort were more likely to have virologic suppression compared to hospital-based patients (adjusted OR = 2.47, 95% CI 1.01–6.04).

Conclusion

Acceptable rates of virologic suppression were achieved using existing rural clinic and community resources in a HC/community-based ART program run by clinical officers and supported by lay volunteers and treatment supporters. The results were equivalent to those of a hospital-based ART program run primarily by doctors.     

Evaluation of Clinical and Immunological Markers for Predicting Virological Failure in a HIV/AIDS Treatment Cohort in Busia,Kenya

Background

In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART).

Methods

In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old) on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4) and immunological (CD4 cell count) criteria, and compared with virological failure (VL >5,000 copies/mL).

Results

Of 926 patients, 123 (13.3%) had clinically defined treatment failure, 53 (5.7%) immunologically defined failure, and 55 (6.0%) virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined) in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively.

Conclusions

In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings.     

Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan,China

Background

Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China''s current HIV treatment program prevents new HIV infections among discordant couples in rural China.

Methods

A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence.

Results

A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup.

Conclusions

ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China''s HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region.     

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background

Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.

Methodology

Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.

Findings

Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.

Conclusion

Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.     

HIV Care Visits and Time to Viral Suppression, 19 U.S. Jurisdictions,and Implications for Treatment,Prevention and the National HIV/AIDS Strategy

Objective

Early and regular care and treatment for human immunodeficiency virus (HIV) infection are associated with viral suppression, reductions in transmission risk and improved health outcomes for persons with HIV. We determined, on a population level, the association of care visits with time from HIV diagnosis to viral suppression.

Methods

Using data from 19 areas reporting HIV-related tests to national HIV surveillance, we determined time from diagnosis to viral suppression among 17,028 persons diagnosed with HIV during 2009, followed through December 2011, using data reported through December 2012. Using Cox proportional hazards models, we assessed factors associated with viral suppression, including linkage to care within 3 months of diagnosis, a goal set forth by the National HIV/AIDS Strategy, and number of HIV care visits as determined by CD4 and viral load test results, while controlling for demographic, clinical, and risk characteristics.

Results

Of 17,028 persons diagnosed with HIV during 2009 in the 19 areas, 76.6% were linked to care within 3 months of diagnosis and 57.0% had a suppressed viral load during the observation period. Median time from diagnosis to viral suppression was 19 months overall, and 8 months among persons with an initial CD4 count ≤350 cells/µL. During the first 12 months after diagnosis, persons linked to care within 3 months experienced shorter times to viral suppression (higher rate of viral suppression per unit time, hazard ratio [HR] = 4.84 versus not linked within 3 months; 95% confidence interval [CI] 4.27, 5.48). Persons with a higher number of time-updated care visits also experienced a shorter time to viral suppression (HR = 1.51 per additional visit, 95% CI 1.49, 1.52).

Conclusions

Timely linkage to care and greater frequency of care visits were associated with faster time to viral suppression with implications for individual health outcomes and for secondary prevention.     

The Impact of Antiretroviral Therapy in a Cohort of HIV Infected Patients Going in and out of the San Francisco County Jail

Background

Jails are an important venue of HIV care and a place for identification, treatment and referral for care. HIV infected inmates in the San Francisco County jail are offered antiretroviral treatment (ART), which many take only while in jail. We evaluated the effect of ART administration in a cohort of jail inmates going in and out of jail over a nine year period.

Methodology/Principal Findings

In this retrospective study, we examined inmates with HIV going in and out of jail. Inmates were categorized by patterns of ART use: continuous ART - ART both in and out of jail, intermittent ART - ART only in jail; never on ART - eligible by national guidelines, but refused ART. CD4 and HIV viral load (VL) were compared over time in these groups. Over a 9 year period, 512 inmates were studied: 388 (76%) on intermittent ART, 79 (15%) on continuous ART and 45(9%) never-on ART. In a linear mixed model analysis, inmates on intermittent ART were 1.43; 95%CI (1.03, 1.99) times and those never on ART were 2.89; 95%CI (1.71, 4.87) times more likely to have higher VL than inmates on continuous ART. Furthermore, Inmates on intermittent ART and never-on ART lost 1.60; 95%CI (1.06, 2.13) and 1.97; 95%CI (0.96, 3.00) more CD4 cells per month, respectively, compared to continuously treated inmates. The continuous ART inmates gained 0.67CD4 cells/month.

Conclusions/Significance

Continuous ART therapy in jail inmate''s benefits CD4 cell counts and control of VL especially compared to those who never took ART. Although jail inmates on intermittent ART were more likely to lose CD4 cells and experience higher VL over time than those on continuous ART, CD4 cell loss was slower in these inmates as compared to inmates never on ART. Further studies are needed to evaluate whether or not intermittent ART provides some benefit in outcome if continuous ART is not possible or likely.     

Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women

Background

Antiretroviral therapy (ART) for HIV infection reconstitutes the immune system and improves survival. However, the rate and extent of CD4+ T cell recovery varies widely. We assessed the impact of several factors on immune reconstitution in a large Kenyan cohort.

Methodology/Principal Findings

HIV-infected female sex workers from a longitudinal cohort, with at least 1 year of pre-ART and 6 months of post-ART follow-up (n = 79), were enrolled in the current study. The median pre-ART follow-up was 4,040 days. CD4 counts were measured biannually and viral loads where available. The median CD4 count at ART initiation was 180 cells/ul, which increased to 339 cells/ul at the most recent study visit. The rate of CD4+ T cell increase on ART was 7.91 cells/month (mean = 13, range −25.92 to 169.4). LTNP status prior to ART initiation did not associate with the rate of CD4 recovery on ART. In univariate analyses, associations were observed for CD4 recovery rate and duration of pre-ART immunosuppression (r = −0.326, p = 0.004) and CD4 nadir (r = 0.284, p = 0.012). In multivariate analysis including age, CD4 nadir, duration of HIV infection, duration of pre-ART immunosuppression, and baseline viral load, only CD4 nadir (p = 0.007) and not duration of immunosupression (p = 0.87) remained significantly associated with the rate of CD4 recovery.

Conclusions/Significance

These data suggest that prior duration of immune suppression does not predict subsequent recovery once ART is initiated and confirm the previous observation that the degree of CD4 depletion prior to ART initiation is the most important determinant of subsequent immune reconstitution.     

Low Rates of Repeat HIV Testing Despite Increased Availability of Antiretroviral Therapy in Rural Tanzania: Findings from 2003–2010

Background

HIV counselling and testing (HCT) services can play an important role in HIV prevention by encouraging safe sexual behaviours and linking HIV-infected clients to antiretroviral therapy (ART). However, regular repeat testing by high-risk HIV-negative individuals is important for timely initiation of ART as part of the ‘treatment as prevention’ approach.

Aim

To investigate HCT use during a round of HIV serological surveillance in northwest Tanzania in 2010, and to explore rates of repeat testing between 2003 and 2010.

Methods

HCT services were provided during the fourth, fifth and sixth rounds of serological surveillance in 2003–2004 (Sero-4), 2006–2007 (Sero-5) and 2010 (Sero-6). HCT services have also been available at a government-run health centre and at other clinics in the study area since 2005. Questionnaires administered during sero-surveys collected information on socio-demographic characteristics, sexual behaviour and reported previous use of HCT services.

Results

The proportion of participants using HCT increased from 9.4% at Sero-4 to 16.6% at Sero-5 and 25.5% at Sero-6. Among participants attending all three sero-survey rounds (n = 2,010), the proportions using HCT twice or more were low, with 11.1% using the HCT service offered at sero-surveys twice or more, and 25.3% having tested twice or more if reported use of HCT outside of sero-surveys was taken into account. In multivariable analyses, individuals testing HIV-positive were less likely to repeat test than individuals testing HIV-negative (aOR 0.17, 95% CI 0.006–0.52).

Discussion/Conclusions

Although HCT service use increased over time, it was disappointing that the proportions ever testing and ever repeat-testing were not even larger, considering the increasing availability of HCT and ART in the study area. There was some evidence that HIV-negative people with higher risk sexual behaviours were most likely to repeat test, which was encouraging in terms of the potential to pick-up those at greatest risk of HIV-infection.     

Refining HIV Risk: The Modifying Effects of Youth,Gender and Education among People Who Inject Drugs in Poland

Objective

The goal of this study was to examine specific factors placing young (aged <30) women who inject drugs at higher risk for HIV, and to establish the need for targeted interventions within this population.

Methods

A national cross-sectional sero-survey was conducted in 2004–2005 in six regions in Poland. A snowball sample of ever-injectors was recruited from drug treatment facilities and the surrounding community. Log-binomial regression was used to estimate adjusted prevalence ratios (PRs).

Results

A total of 491 injection drug users younger than 30 were recruited, of whom 159 were women and 332 were men. The prevalence of HIV was 16.4% and 9.6% among women and men, respectively. In multivariate analysis, young female injectors whose education terminated at the primary level were more likely to be HIV-positive compared to males with a similar level of education (PR = 3.34, 95% CI = 1.86–6.00) and more highly educated women (PR = 4.16, 95% CI = 2.21–7.82).

Conclusions

This study confirms an elevated risk of HIV among under-educated young women. Suggestions for specific interventions to reduce HIV transmission are presented. Additional research is needed to quantify the differential distribution of risk behaviors which amplify their likelihood of transmission.