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2.  Improvements in HIV treatment outcomes among indigenous and non-indigenous people who use illicit drugs in a Canadian setting 
Introduction
In many settings worldwide, members of indigenous groups experience a disproportionate burden of HIV. In Canada, there is an urgent need to improve HIV treatment outcomes for indigenous people living with HIV (IPLWH), to not only reduce HIV/AIDS-associated morbidity and mortality but also curb elevated rates of viral transmission. Thus, by comparing indigenous and non-indigenous participants in an ongoing longitudinal cohort of HIV-positive people who use illicit drugs, we sought to investigate longitudinal changes in three HIV treatment indicators for IPLWH who use illicit drugs during a community-wide treatment-as-prevention (TasP) initiative in British Columbia, Canada.
Methods
We used data from the ACCESS study, an ongoing observational prospective cohort of HIV-positive illicit drug users recruited from community settings in Vancouver, British Columbia. Cohort data are linked to comprehensive retrospective and prospective clinical records in a setting of no-cost HIV/AIDS treatment and care. We used multivariable generalized estimating equations (GEE) to evaluate longitudinal changes in the proportion of participants with exposure to antiretroviral therapy (ART) in the previous 180 days, optimal adherence to ART (i.e. ≥95% vs. <95%) and non-detectable HIV-1 RNA viral load (VL <50 copies/mL plasma).
Results
Between 2005 and 2014, 845 individuals were recruited, including 326 (39%) self-reporting any indigenous ancestry, and contributed 6732 interviews and 13,495 VL measurements. Among indigenous participants, the proportion with recent ART increased from 51 to 94% and non-detectable VL from 23 to 65%. In multivariable models, later interview period was positively associated with recent ART (adjusted odds ratio (AOR)=1.16 per interview period, 95% confidence interval (CI): 1.11 to 1.20) and non-detectable VL (AOR=1.07, 95% CI: 1.04 to 1.10). In adjusted models comparing indigenous and non-indigenous participants, we did not observe differences between the two groups (all p>0.1).
Conclusions
In this large and long-term study involving community-recruited HIV-positive illicit drug users, we observed a substantial and increasing proportion of indigenous participants reach several important thresholds in HIV care at rates indistinguishable from non-indigenous participants. The current findings highlight the important role of TasP on vulnerable populations in this setting and contribute to the evidence base supporting the immediate scale-up of ART to address HIV/AIDS-associated morbidity, mortality and viral transmission.
doi:10.7448/IAS.19.1.20617
PMCID: PMC4837333  PMID: 27094914
HIV; AIDS; indigenous; highly active antiretroviral therapy; HAART; plasma HIV-1 RNA viral load; treatment-as-prevention
3.  Structural drivers and social protection: mechanisms of HIV risk and HIV prevention for South African adolescents 
Introduction
Social protection is high on the HIV-prevention agenda for youth in sub-Saharan Africa. However, questions remain: How do unconditional cash transfers work? What is the effect of augmenting cash provision with social care? And can “cash plus care” social protection reduce risks for adolescents most vulnerable to infection? This study tackles these questions by first identifying mediated pathways to adolescent HIV risks and then examining potential main and moderating effects of social protection in South Africa.
Methods
This study was a prospective observational study of 3515 10-to-17-year-olds (56.7% female; 96.8% one-year retention). Within randomly selected census areas in four rural and urban districts in two South African provinces, all homes with a resident adolescent were sampled between 2009/2010 and 2011/2012. Measures included 1) potential structural drivers of HIV infection such as poverty and community violence; 2) HIV risk behaviours; 3) hypothesized psychosocial mediating factors; and 4) types of social protection involving cash and care. Using gender-disaggregated analyses, longitudinal mediation models were tested for potential main and moderating effects of social protection.
Results
Structural drivers were associated with increased onset of adolescent HIV risk behaviour (p<0.001, B=0.06, SE=0.01), fully mediated by increased psychosocial problems. Both cash and care aspects of social protection were associated with reductions in HIV risk behaviour and psychosocial deprivations. In addition, cash social protection moderated risk pathways: for adolescent girls and boys experiencing more acute structural deprivation, social protection had the greatest associations with HIV risk prevention (e.g. moderation effects for girls: B=−0.08, p<0.002 between structural deprivation and psychosocial problems, and B=−0.07, p<0.001 between psychosocial problems and HIV risk behaviour).
Conclusions
Adolescents with the greatest structural deprivation are at higher risk of HIV, but social protection has the greatest prevention effects for the most vulnerable. Social protection comprising unconditional cash plus care was associated with reduced risk pathways through moderation and main effects, respectively. Our findings suggest the importance of social protection within a combination package of HIV-prevention approaches.
doi:10.7448/IAS.19.1.20646
PMCID: PMC4834365  PMID: 27086838
prevention; adolescents; social protection; abuse; education; poverty
4.  Time for full inclusion of community actions in the response to AIDS 
Introduction
Community action, including activism, advocacy and service delivery, has been crucially important in the global response to AIDS from the beginning of the epidemic and remains one of its defining features. This indispensable contribution has been increasingly acknowledged in strategic planning documents from UNAIDS, the Global Fund to fight AIDS, Tuberculosis and Malaria, the World Bank, the World Health Organization and other organizations. A growing body of literature demonstrates that community-based services can have measurable impact, serve populations that are not accessing public health services and reach people at scale.
Discussion
Recognition of the powerful potential role of community has not translated into full incorporation of community responses in programme planning or financing, and communities are still not fully understood as true assets within overall systems for health. The diverse community contributions remain seriously underappreciated and under-resourced in national responses.
Conclusions
It is time for a paradigm shift in how we think about, plan and finance community-based responses to HIV in order to achieve improved impact and move toward ending the epidemic. We must utilize the unique strengths of communities in creating resilient and sustainable systems for health. There are several priorities for immediate attention, including agreement on the need to nurture truly comprehensive systems for health that include public, private and community activities; re-examination of donor and national funding processes to ensure community is strategically included; improvement of data systems to capture the full spectrum of health services; and improved accountability frameworks for overall health systems. Health planning and financing approaches run by governments and donors should institutionalize consideration of how public, community and private health services can strategically contribute to meeting service needs and accomplishing public health targets.
doi:10.7448/IAS.19.1.20712
PMCID: PMC4833769  PMID: 27083149
AIDS; HIV; community; services; health system; advocacy
5.  Changes in self-reported HIV testing during South Africa's 2010/2011 national testing campaign: gains and shortfalls 
Objectives
HIV counselling and testing is critical to HIV prevention and treatment efforts. Mass campaigns may be an effective strategy to increase HIV testing in countries with generalized HIV epidemics. We assessed the self-reported uptake of HIV testing among individuals who had never previously tested for HIV, particularly those in high-risk populations, during the period of a national, multisector testing campaign in South Africa (April 2010 and June 2011).
Design
This study was a prospective cohort study.
Methods
We analyzed data from two waves (2010/2011, n=16,893; 2012, n=18,707) of the National Income Dynamics Study, a nationally representative cohort that enabled prospective identification of first-time testers. We quantified the number of adults (15 years and older) testing for the first time nationally. To assess whether the campaign reached previously underserved populations, we examined changes in HIV testing coverage by age, gender, race and province sub-groups. We also estimated multivariable logistic regression models to identify socio-economic and demographic predictors of first-time testing.
Results
Overall, the proportion of adults ever tested for HIV increased from 43.7% (95% confidence interval (CI): 41.48, 45.96) to 65.2% (95% CI: 63.28, 67.10) over the study period, with approximately 7.6 million (95% CI: 6,387,910; 8,782,986) first-time testers. Among black South Africans, the country's highest HIV prevalence sub-group, HIV testing coverage improved among poorer and healthier individuals, thus reducing gradients in testing by wealth and health. In contrast, HIV testing coverage remained lower for men, younger individuals and the less educated, indicating persistent if not widening disparities by gender, age and education. Large geographic disparities in coverage also remained as of 2012.
Conclusions
Mass provision of HIV testing services can be effective in increasing population coverage of HIV testing. The geographic and socio-economic disparities in programme impacts can help guide best practices for future efforts. These efforts should focus on hard-to-reach populations, including men and less-educated individuals.
doi:10.7448/IAS.19.1.20658
PMCID: PMC4829657  PMID: 27072532
HIV/AIDS; testing; HCT; southern Africa; socio-economic determinants; disparities
6.  Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression 
Introduction
We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS).
Methods
Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care.
Results
Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission.
Conclusions
HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings.
doi:10.7448/IAS.19.1.20636
PMCID: PMC4827101  PMID: 27065108
HIV Care Continuum; Latin America; retention; cART use; viral suppression; cohort studies
7.  A systematic review of interventions to improve prevention of mother-to-child HIV transmission service delivery and promote retention 
Introduction
The success of prevention of mother-to-child transmission of HIV (PMTCT) is dependent upon high retention of mother-infant pairs within these programmes. This is a systematic review to evaluate the effectiveness of interventions that aim to improve PMTCT service delivery and promote retention throughout the PMTCT steps.
Methods
Selected databases were searched for studies published in English (up to September 2015). Outcomes of interest included antiretroviral (ARV) drugs or antiretroviral therapy (ART) initiation among HIV-positive pregnant and/or breastfeeding women and their infants, retention into PMTCT programs, the uptake of early infant diagnosis (EID) of HIV and infant HIV status. Risk ratios and random-effect meta-analysis were used in the analysis.
Results
Interventions assessed in the 34 identified studies included male partner involvement in PMTCT, peer mentoring, the use of community health workers (CHWs), mobile phone-based reminders, conditional cash transfer, training of midwives, integration of PMTCT services and enhanced referral. Five studies (two randomized) that evaluated mobile phone-based interventions showed a statistically significant increase (pooled RR 1.18; 95% CI 1.05 to 1.32, I2=83%) in uptake of EID of HIV at around six weeks postpartum. Male partner involvement in PMTCT was associated with reductions in infant HIV transmission (pooled RR 0.61; 95% CI 0.39 to 0.94, I2=0%) in four studies (one randomized). Four studies (three randomized) that were grounded on psychological interventions reported non-significant results (pooled RR 1.01; 95% CI 0.93 to 1.09, I2=69%) in increasing ARV/ART uptake among HIV-positive pregnant and/or breastfeeding women and infant HIV testing (pooled RR 1.00; 95% CI 0.94 to 1.07, I2=45%). The effect of the other interventions on the effectiveness of improving PMTCT uptake was unclear. Heterogeneity of interventions limits these findings.
Conclusions
Our findings indicate that mobile phone-based reminders may increase the uptake of EID of HIV. Studies on male partner involvement in PMTCT reported reductions in infant HIV transmission. Stronger evidence is needed and future studies should determine the long-term effects of these interventions in improving retention throughout the PMTCT steps.
doi:10.7448/IAS.19.1.20309
PMCID: PMC4824870  PMID: 27056361
infant ART initiation; conditional cash transfer; male involvement; peer mentoring; community health worker; home visit; mobile phone-based reminders; integrated PMTCT services
8.  A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts 
Introduction
Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries.
Methods
Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries.
Results
Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm3. Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America.
Conclusions
These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.
doi:10.7448/IAS.19.1.20707
PMCID: PMC4821890  PMID: 27049052
Map; HIV indicators; CD4 T-lymphocyte count; retention in care; antiretroviral therapy; HIV RNA suppression; North America; Central America; South America; implementation science
9.  The risks of partner violence following HIV status disclosure, and health service responses: narratives of women attending reproductive health services in Kenya 
Introduction
For many women living with HIV (WLWH), the disclosure of positive status can lead to either an extension of former violence or new conflict specifically associated with HIV status disclosure. This study aims to explore the following about WLWH: 1. the women's experiences of intimate partner violence (IPV) risks following disclosure to their partners; 2. an analysis of the women's views on the role of health providers in preventing and addressing IPV, especially following HIV disclosure.
Methods
Thirty qualitative interviews were conducted with purposively selected WLWH attending clinics in Kenya. Data were coded using NVivo 9 and analyzed thematically.
Results
Nearly one third of the respondents reported experiencing physical and/or emotional violence inflicted by their partners following the sero-disclosure, suggesting that HIV status disclosure can be a period of heightened risk for partner stigma and abuse, and financial withdrawal, and thus should be handled with caution. Sero-concordance was protective for emotional and verbal abuse once the partner knew his positive status, or knew the woman knew his status. Our results show acceptance of the role of the health services in helping prevent and reduce anticipated fear of partner stigma and violence as barriers to HIV disclosure. Some of the approaches suggested by our respondents included couple counselling, separate counselling sessions for men, and facilitated disclosure. The women's narratives illustrate the importance of integrating discussions on risks for partner violence and fear of disclosure into HIV counselling and testing, helping women develop communication skills in how to disclose their status, and reducing fear about marital separation and break-up. Women in our study also confirmed the key role of preventive health services in reducing blame for HIV transmission and raising awareness on HIV as a chronic disease. However, several women reported receiving no counselling on safe disclosure of HIV status.
Conclusion
Integration of partner violence identification and care into sexual, reproductive and HIV services for WLWH could be a way forward. The health sector can play a preventive role by sensitizing providers to the potential risks for partner violence following disclosure and ensuring that the women's decision to disclose is fully informed and voluntary.
doi:10.7448/IAS.19.1.20766
PMCID: PMC4819069  PMID: 27037140
HIV-positive women; women living with HIV; intimate partner violence; violence against women; HIV disclosure
10.  Survival benefits of antiretroviral therapy in Brazil: a model-based analysis 
Objective
In Brazil, universal provision of antiretroviral therapy (ART) has been guaranteed free of charge to eligible HIV-positive patients since December 1996. We sought to quantify the survival benefits of ART attributable to this programme.
Methods
We used a previously published microsimulation model of HIV disease and treatment (CEPAC-International) and data from Brazil to estimate life expectancy increase for HIV-positive patients initiating ART in Brazil. We divided the period of 1997 to 2014 into six eras reflecting increased drug regimen efficacy, regimen availability and era-specific mean CD4 count at ART initiation. Patients were simulated first without ART and then with ART. The 2014-censored and lifetime survival benefits attributable to ART in each era were calculated as the product of the number of patients initiating ART in a given era and the increase in life expectancy attributable to ART in that era.
Results
In total, we estimated that 598,741 individuals initiated ART. Projected life expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to 11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6, respectively. Of the total projected lifetime survival benefit of 9.3 million life-years, 16% (or 1.5 million life-years) has been realized as of December 2014.
Conclusions
Provision of ART through a national programme has led to dramatic survival benefits in Brazil, the majority of which are still to be realized. Improvements in initial and subsequent ART regimens and higher CD4 counts at ART initiation have contributed to these increasing benefits.
doi:10.7448/IAS.19.1.20623
PMCID: PMC4814587  PMID: 27029828
HIV; Brazil; highly active antiretroviral therapy; survival; modelling; Latin America
13.  Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013 
Introduction
The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso.
Methods
All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.
Results
Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.
Conclusions
Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.
doi:10.7448/IAS.19.1.20601
PMCID: PMC4808141  PMID: 27015798
children; West Africa; HIV; acceptability; early antiretroviral therapy; linkage to care; access to care
14.  Factors associated with loss to follow-up among women in Option B+ PMTCT programme in northeast Ethiopia: a retrospective cohort study 
Introduction
Ethiopia has recently adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women (Option B+ strategy), regardless of CD4 count or clinical stage. However, the exact timing and predictors of loss to follow-up (LFU) are unknown. Thus, we examined the levels and determinants of LFU under Option B+ among pregnant and breastfeeding women initiated on lifelong ART for prevention of mother-to-child transmission (PMTCT) in Ethiopia.
Methods
We conducted a retrospective cohort study among 346 pregnant and breastfeeding women who started ART at 14 public health facilities in northeast Ethiopia from March 2013 to April 2015. We defined LFU as 90 days since the last clinic visit among those not known to have died or transferred out. We used Kaplan-Meier and Cox proportional hazards regression to estimate cumulative LFU and identify the predictors of LFU, respectively.
Results
Of the 346 women included, 88.4% were pregnant and the median follow-up was 13.7 months. Overall, 57 (16.5%) women were LFU. The cumulative proportions of LFU at 6, 12 and 24 months were 11.9, 15.7 and 22.6%, respectively. The risk of LFU was higher in younger women (adjusted hazard ratio (aHR) 18 to 24 years/30 to 40 years: 2.3; 95% confidence interval (CI): 1.2 to 4.5), in those attending hospitals compared to those attending health centres (aHR: 1.8; 95% CI: 1.1 to 3.2), in patients starting ART on the same day of diagnosis (aHR: 1.85; 95% CI: 1.1 to 3.2) and missing CD4 cell counts at ART initiation (aHR: 2.3; 95% CI: 1.2 to 4.4).
Conclusions
The level of LFU we found in this study is comparable with previous findings from other resource-limited settings. However, high early LFU shortly after ART initiation is still a major problem. LFU was high among younger women, those initiating ART on the day of HIV diagnosis, those missing baseline CD4 count and those attending hospitals. Thus, targeted HIV care and treatment programmes for these patients should be part of future interventions to improve retention in care under the Option B+ PMTCT programme.
doi:10.7448/IAS.19.1.20662
PMCID: PMC4803835  PMID: 27005750
loss to follow-up; Option B+; Ethiopia
15.  Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America 
Introduction
Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America.
Methods
HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts.
Results
The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57).
Conclusions
HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.
doi:10.7448/IAS.19.1.20684
PMCID: PMC4800379  PMID: 26996992
HIV; antiretroviral therapy; highly active; mortality; Latin America; North America; cohort studies
16.  Estimating HIV incidence among key affected populations in China from serial cross-sectional surveys in 2010–2014 
Introduction
HIV incidence is an important measure for monitoring the development of the epidemic, but it is difficult to ascertain. We combined serial HIV prevalence and mortality data to estimate HIV incidence among key affected populations (KAPs) in China.
Methods
Serial cross-sectional surveys were conducted among KAPs from 2010 to 2014. Trends in HIV prevalence were assessed by the Cochran-Armitage test, adjusted by risk group. HIV incidence was estimated from a mathematical model that describes the relationship between changes in HIV incidence with HIV prevalence and mortality.
Results
The crude HIV prevalence for the survey samples remained stable at 1.1 to 1.2% from 2010 to 2014. Among drug users (DUs), HIV prevalence declined from 4.48 to 3.29% (p<0.0001), and among men who have sex with men (MSM), HIV prevalence increased from 5.73 to 7.75% (p<0.0001). Changes in HIV prevalence among female sex workers (FSWs) and male patients of sexually transmitted disease clinics were more modest but remained statistically significant (all p<0.0001). The MSM population had the highest incidence estimates at 0.74% in 2011, 0.59% in 2012, 0.57% in 2013 and 0.53% in 2014. Estimates of the annual incidence for DUs and FSWs were very low and may not be reliable.
Conclusions
Serial cross-sectional prevalence data from representative samples may be another approach to construct approximate estimates of national HIV incidence among key populations. We observed that the MSM population had the highest incidence for HIV among high-risk groups in China, and we suggest that interventions targeting MSM are urgently needed to curb the growing HIV epidemic.
doi:10.7448/IAS.19.1.20609
PMCID: PMC4796775  PMID: 26989062
HIV; cross-sectional survey; incidence; prevalence; mortality; key affected populations
17.  Prevalence of hepatitis B and C viruses in HIV-positive patients in China: a cross-sectional study 
Introduction
Liver disease related to hepatitis B (HBV) and hepatitis C (HCV) may temper the success of antiretroviral therapy (ART) in China. Limited data exist on their prevalence in HIV-positive Chinese. A multi-centre, cross-sectional study was carried out to determine the prevalence and disease characteristics of HBV and HCV co-infection in HIV-positive patients across 12 provinces.
Methods
HIV-positive ART-naïve patients were recruited from two parent cohorts established during November 2008–January 2010 and August 2012–September 2014. Hepatitis B surface antigen (HBsAg), hepatitis B e antigen and HCV antibody (anti-HCV) status were retrieved from parent databases at the visit prior to ART initiation. HBV DNA was then determined in HBsAg+ patients. HCV RNA was quantified in anti-HCV+ patients. Aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 (FIB4) were calculated. Chi-square test, Kruskal–Wallis test and logistic regression were used for statistical analysis, as appropriate.
Results
Of 1944 HIV-positive patients, 186 (9.5%) were HIV–HBV co-infected and 161 (8.3%) were HIV–HCV co-infected. The highest HIV–HBV prevalence (14.5%) was in Eastern China while the highest HIV–HCV prevalence was in the Central region (28.2%). HIV–HBV patients had lower median CD4 + T cell count (205 cells/μL) than either HIV monoinfected (242 cells/μL, P=0.01) or HIV–HCV patients (274 cells/μL, P=0.001). Moderate-to-significant liver disease was present in >65% of the HIV–HCV, ~35% of the HIV–HBV and ~20% of the HIV monoinfected patients. Independent associations with moderate-to-significant liver disease based on APRI included HBV (Odds ratio, OR 2.37, P < 0.001), HCV (OR 9.64, P<0.001), CD4 count≤200 cells/μL (OR 2.55, P<0.001) and age ≥30 years (OR 1.80, P=0.001).
Conclusions
HBV and HCV prevalence is high in HIV-positive Chinese and differs by geographic region. HBV and HCV co-infection and HIV monoinfection are risks for moderate-to-significant liver disease. Only HIV–HBV is associated with greater HIV-related immunosuppression. Incorporating screening and management of hepatitis virus infections into Chinese HIV programmes is needed.
doi:10.7448/IAS.19.1.20659
PMCID: PMC4793284  PMID: 26979535
HIV; hepatitis B virus; hepatitis C virus; co-infection; prevalence; liver disease; CD4+T cell count
18.  Same day HIV diagnosis and antiretroviral therapy initiation affects retention in Option B+ prevention of mother-to-child transmission services at antenatal care in Zomba District, Malawi 
Introduction
Data from the Option B+ prevention of mother-to-child transmission (PMTCT) program in Malawi show considerable variation between health facilities in retention on antiretroviral therapy (ART). In a programmatic setting, we studied whether the “model of care,” based on the degree of integration of antenatal care (ANC), HIV testing and counselling (HTC) and ART service provision–influenced uptake of and retention on ART.
Methods
We conducted a retrospective cohort study of pregnant women seeking ANC at rural primary health facilities in Zomba District, Malawi. Data were extracted from standardized national ANC registers, ART registers and ART master cards. The “model of care” of Option B+ service delivery was determined at each health facility, based on the degree of integration of ANC, HTC and ART. Full integration (Model 1) of HTC and ART initiation at ANC was compared with integration of HTC only into ANC services (Model 2) with subsequent referral to an existing ART clinic for treatment initiation.
Results and discussion
A total of 10,528 women were newly registered at ANC between October 2011 and March 2012 in 23 rural health facilities (12 were Model 1 and 11 Model 2). HIV status was ascertained in 8,572 (81%) women. Among 914/8,572 (9%) HIV-positive women enrolling at ANC, 101/914 (11%) were already on ART; of those not on treatment, 456/813 (56%) were started on ART. There was significantly higher ART uptake in Model 1 compared with Model 2 sites (63% vs. 51%; p=0.001), but significantly lower ART retention in Model 1 compared with Model 2 sites (79% vs. 87%; p=0.02). Multivariable analysis showed that initiation of ART on the same day as HIV diagnosis, but not model of care, was independently associated with reduced retention in the first six months (adjusted odds ratio 2.27; 95% CI: 1.34–3.85; p=0.002).
Conclusions
HIV diagnosis and treatment on the same day was associated with reduced retention on ART, independent of the level of PMTCT service integration at ANC.
doi:10.7448/IAS.19.1.20672
PMCID: PMC4789547  PMID: 26976377
PMTCT; Option B+; Malawi; service delivery model; ANC–ART integration; retention on ART
19.  Uptake of early infant diagnosis in Thailand’s national program for preventing mother-to-child HIV transmission and linkage to care, 2008–2011 
Introduction
Early infant diagnosis (EID) has been a component of Thailand's prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment.
Methods
Infant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand's National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage.
Results
For 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p<0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p=0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p<0.001).
Conclusions
EID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.
doi:10.7448/IAS.19.1.20511
PMCID: PMC4788772  PMID: 26968214
EID; prevention of mother-to-child HIV transmission; Thailand; national PMTCT programme evaluation; linkage to care; antiretroviral therapy; HIV
20.  Hospitalizations among HIV controllers and persons with medically controlled HIV in the U.S. Military HIV Natural History Study 
Introduction
HIV controllers (HICs) experience relatively low-level viraemia and CD4 preservation without antiretroviral therapy (ART), but also immune activation that may predispose to adverse clinical events such as cardiovascular disease and hospitalization. The objective of this study was to characterize the rates and reasons for hospitalization among HICs and persons with medically controlled HIV.
Methods
Subjects with consistently well-controlled HIV were identified in the U.S. Military HIV Natural History Study. ART prescription and HIV-1 RNA data were used to categorize subjects as HICs or medically controlled as defined by ≥3 HIV-1 RNA measurements ≤2000 or ≤400 copies/mL, respectively, representing the majority of measurements spanning ≥12 months. Hospitalizations were tallied and assigned diagnostic categories. All-cause hospitalization rates were compared between groups using negative binomial regression.
Results and discussion
Of 3106 subjects followed from 2000 to 2013, 221 were HICs, including 33 elite (1.1%) and 188 viraemic (6.0%) controllers, who contributed 882 person-years (PY) of observation time. An additional 870 subjects with medically controlled HIV contributed 4217 PY. Mean hospitalization rates were 9.4/100 PY among HICs and 8.8/100 PY among medically controlled subjects. Non-AIDS-defining infections were the most common reason for hospitalization (2.95/100 PY and 2.70/100 PY, respectively) and rates of cardiovascular hospitalization were similar in both groups (0.45/100 PY and 0.76/100 PY). There was no difference in hospitalization rate for HICs compared with subjects with medically controlled HIV (adjusted incidence rate ratio 1.15 [95% confidence interval 0.80 to 1.65]).
Conclusions
All-cause and cardiovascular hospitalization rates did not differ between HICs and persons with medically controlled HIV. Non-AIDS defining infections were common in this young, healthy, predominantly male cohort of military personnel and beneficiaries.
doi:10.7448/IAS.19.1.20524
PMCID: PMC4783305  PMID: 26955965
HIV; HIV non-progressors; patient admission; hospitalization; highly active antiretroviral therapy
21.  Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era 
Introduction
HIV infection leads to a disturbed T-cell homeostasis, featured by a depletion of CD4 T-cells and a persistent elevation of CD8 T-cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T-cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.
Methods
A comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T-cell dynamics in HIV infection and following antiretroviral therapy (ART).
Discussion
Normalization of CD8 counts is seldom observed even with optimal CD4 recovery following long-term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long-term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non-AIDS-related clinical events independent of CD4 T-cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T-cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.
Conclusions
Persistence of CD8 T-cell elevation in treated HIV-infected patients is associated with an increased risk of non-AIDS-related events. Now that advances in ART have led to decreased AIDS-related opportunistic diseases, more attention has been focused on reducing non-AIDS events and normalizing persistent CD8 T-cell elevation.
doi:10.7448/IAS.19.1.20697
PMCID: PMC4779330  PMID: 26945343
HIV; antiretroviral therapy; CD8 T-cell persistence; bystander activation; T-cell exhaustion
22.  Cost-effectiveness of screening for anal cancer using regular digital ano-rectal examinations in men who have sex with men living with HIV 
Introduction
Anal cancer in men who have sex with men (MSM) living with HIV is an important issue but there are no consistent guidelines for how to screen for this cancer. In settings where screening with anal cytology is unavailable, regular anal examinations have been proposed in some guidelines but their cost-effectiveness is unknown.
Methods
Our objective was to estimate the cost-effectiveness of regular anal examinations to screen for anal cancer in HIV-positive MSM living in Australia using a probabilistic Markov model. Data sources were based on the medical literature and a clinical trial of HIV-positive MSM receiving an annual anal examination in Australia. The main outcome measures for calculating effectiveness were undiscounted and discounted (at 3%) lifetime costs, life years gained, quality-adjusted life years (QALY) gained and incremental cost-effectiveness ratio (ICER).
Results
Base-case analysis estimated the average cost of screening for and management of anal cancer ranged from $195 for no screening to $1,915 for lifetime annual screening of men aged ≥ 50. Screening of men aged ≥ 50 generated ICERs of $29,760 per QALY gained (for screening every four years), $32,222 (every three years) and $45,484 (every two years). Uncertainty for ICERs was mostly influenced by the cost (financially and decrease in quality of life) from a false-positive result, progression rate of anal cancer, specificity of the anal examination, the probability of detection outside a screening program and the discount rate.
Conclusions
Screening for anal cancer by incorporating regular anal examinations into routine HIV care for MSM aged ≥ 50 is most likely to be cost-effective by conventional standards. Given that anal pap smears are not widely available yet in many clinical settings, regular anal exams for MSM living with HIV to detect anal cancer earlier should be implemented.
doi:10.7448/IAS.19.1.20514
PMCID: PMC4778406  PMID: 26942721
HIV; anal cancer; men who have sex with men; cost-effectiveness; screening
24.  In the interests of time: improving HIV allocative efficiency modelling via optimal time-varying allocations 
Introduction
International investment in the response to HIV and AIDS has plateaued and its future level is uncertain. With many countries committed to ending the epidemic, it is essential to allocate available resources efficiently over different response periods to maximize impact. The objective of this study is to propose a technique to determine the optimal allocation of funds over time across a set of HIV programmes to achieve desirable health outcomes.
Methods
We developed a technique to determine the optimal time-varying allocation of funds (1) when the future annual HIV budget is pre-defined and (2) when the total budget over a period is pre-defined, but the year-on-year budget is to be optimally determined. We use this methodology with Optima, an HIV transmission model that uses non-linear relationships between programme spending and associated programmatic outcomes to quantify the expected epidemiological impact of spending. We apply these methods to data collected from Zambia to determine the optimal distribution of resources to fund the right programmes, for the right people, at the right time.
Results and discussion
Considering realistic implementation and ethical constraints, we estimate that the optimal time-varying redistribution of the 2014 Zambian HIV budget between 2015 and 2025 will lead to a 7.6% (7.3% to 7.8%) decrease in cumulative new HIV infections compared with a baseline scenario where programme allocations remain at 2014 levels. This compares to a 5.1% (4.6% to 5.6%) reduction in new infections using an optimal allocation with constant programme spending that recommends unrealistic programmatic changes. Contrasting priorities for programme funding arise when assessing outcomes for a five-year funding period over 5-, 10- and 20-year time horizons.
Conclusions
Countries increasingly face the need to do more with the resources available. The methodology presented here can aid decision-makers in planning as to when to expand or contract programmes and to which coverage levels to maximize impact.
doi:10.7448/IAS.19.1.20627
PMCID: PMC4770825  PMID: 26928810
allocative efficiency; HIV/AIDS; mathematical modelling; Optima; time-varying optimization; Zambia
25.  The role of partners’ educational attainment in the association between HIV and education amongst women in seven sub-Saharan African countries 
Introduction
Individuals’ educational attainment has long been considered as a risk factor for HIV. However, little attention has been paid to the association between partner educational attainment and HIV infection.
Methods
We conducted cross-sectional analysis of young women (aged 15–34) in 14 Demographic and Health Surveys from seven sub-Saharan Africa (SSA) countries with generalized HIV epidemics. We measured the degree of similarity in educational attainment (partner homophily) in 75,373 partnerships and evaluated the correlation between homophily and female HIV prevalence at the survey cluster level. We then used logistic regression to assess whether own and partner educational attainment was associated with HIV serostatus amongst 38,791 women.
Results
Educational attainment was positively correlated within partnerships in both urban and rural areas of every survey (Newman assortativity coefficients between 0.09 and 0.44), but this correlation was not ecologically associated with HIV prevalence. At the individual level, larger absolute differences between own and partner educational attainment were associated with significantly higher HIV prevalence amongst women. This association was heterogeneous across countries, but not between survey waves. In contrast to other women, for those aged 25–34 who had secondary or higher education, a more-educated partner was associated with lower HIV prevalence.
Conclusions
HIV prevalence amongst women in SSA is associated not only with one's own education but also with that of one's partner. These findings highlight the importance of understanding how partners place individuals at risk of infection and suggest that HIV prevention efforts may benefit from considering partner characteristics.
doi:10.7448/IAS.19.1.20038
PMCID: PMC4762222  PMID: 26902392
sub-Saharan Africa; education; sexual partnerships; homophily; HIV; partner characteristics

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