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1.  Concurrent partnerships in Cape Town, South Africa: race and sex differences in prevalence and duration of overlap 
Introduction
Concurrent partnerships (CPs) have been suggested as a risk factor for transmitting HIV, but their impact on the epidemic depends upon how prevalent they are in populations, the average number of CPs an individual has and the length of time they overlap. However, estimates of prevalence of CPs in Southern Africa vary widely, and the duration of overlap in these relationships is poorly documented. We aim to characterize concurrency in a more accurate and complete manner, using data from three disadvantaged communities of Cape Town, South Africa.
Methods
We conducted a sexual behaviour survey (n=878) from June 2011 to February 2012 in Cape Town, using Audio Computer-Assisted Self-Interviewing to collect sexual relationship histories on partners in the past year. Using the beginning and end dates for the partnerships, we calculated the point prevalence, the cumulative prevalence and the incidence rate of CPs, as well as the duration of overlap for relationships begun in the previous year. Linear and binomial regression models were used to quantify race (black vs. coloured) and sex differences in the duration of overlap and relative risk of having CPs in the past year.
Results
The overall point prevalence of CPs six months before the survey was 8.4%: 13.4% for black men, 1.9% for coloured men, 7.8% black women and 5.6% for coloured women. The median duration of overlap in CPs was 7.5 weeks. Women had less risk of CPs in the previous year than men (RR 0.43; 95% CI: 0.32–0.57) and black participants were more at risk than coloured participants (RR 1.86; 95% CI: 1.17–2.97).
Conclusions
Our results indicate that in this population the prevalence of CPs is relatively high and is characterized by overlaps of long duration, implying there may be opportunities for HIV to be transmitted to concurrent partners.
doi:10.7448/IAS.18.1.19372
PMCID: PMC4334769
concurrent partnerships; sexual concurrency; HIV prevention; South Africa; sexual behaviour and HIV; sexual risk behaviour
2.  Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia 
Introduction
Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU.
Methods
Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naïve adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay.
Results
Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p<0.001), more often received tuberculosis treatment during follow-up (adjusted HR=1.71; 95% CI: 1.25–2.35) and more often had bacteriologically confirmed tuberculosis (OR=1.67; 95% CI: 0.94–2.96). LTBI was equally prevalent among people with and without a history of IDU (29.1 vs. 30.4%, NS). The risk estimates did not change after adjustment for CD4 cell count or ART.
Conclusions
HIV-positive individuals with a history of IDU in Indonesia have more active tuberculosis, with similar rates of LTBI. Within the HIV clinic, LTBI screening and isoniazid preventive therapy may be prioritized to patients with a history of IDU.
doi:10.7448/IAS.18.1.19317
PMCID: PMC4331401  PMID: 25690530
cohort studies; Mycobacterium tuberculosis; human immunodeficiency virus; substance abuse; intravenous; latent tuberculosis infection
3.  Subsidized optimal ART for HIV-positive temporary residents of Australia improves virological outcomes: results from the Australian HIV Observational Database Temporary Residents Access Study 
Introduction
HIV-positive (HIV+) temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART) which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD) Temporary Residents Access Study (ATRAS) and to determine the short- and long-term outcomes of receiving (subsidized) optimal ART and the impact on onwards HIV transmission.
Methods
ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD) and the proportion with undetectable (<50 copies/ml) HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load.
Results
A total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml) and the median CD4 cell count was 343 cells/µl (IQR: 222–479). At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load.
Conclusions
The immunological and virological improvements highlight the importance of supplying optimal ART to this vulnerable population. The increase in proportion with undetectable HIV viral load shows the potentially significant impact on HIV transmission in addition to the personal health benefit for each individual.
doi:10.7448/IAS.18.1.19392
PMCID: PMC4327894  PMID: 25680919
antiretroviral therapy; treatment access; temporary residents; HIV-positive
4.  Prevalence and correlates of HIV among men who have sex with men in Tijuana, Mexico 
Introduction
Men who have sex with men (MSM) in developing countries such as Mexico have received relatively little research attention. In Tijuana, Mexico, a border city experiencing a dynamic HIV epidemic, data on MSM are over a decade old. Our aims were to estimate the prevalence and examine correlates of HIV infection among MSM in this city.
Methods
We conducted a cross-sectional study of 191 MSM recruited through respondent-driven sampling (RDS) in 2012. Biological males over the age of 18 who resided in Tijuana and reported sex with a male in the past year were included. Participants underwent interviewer-administered surveys and rapid tests for HIV and syphilis with confirmation.
Results
A total of 33 MSM tested positive for HIV, yielding an RDS-adjusted estimated 20% prevalence. Of those who tested positive, 89% were previously unaware of their HIV status. An estimated 36% (95% CI: 26.4–46.5) had been tested for HIV in the past year, and 30% (95% CI: 19.0–40.0) were estimated to have ever used methamphetamine. Independent correlates of being infected with HIV were methamphetamine use (odds ratio [OR]=2.24, p=0.045, 95% CI: 1.02, 4.92) and active syphilis infection (OR=4.33, p=0.01, 95% CI: 1.42, 13.19).
Conclusions
Our data indicate that MSM are a key sub-population in Tijuana at higher risk for HIV. Tijuana would also appear to have the highest proportion among upper-middle-income countries of HIV-positive MSM who are unknowingly infected. More HIV prevention research on MSM is urgently needed in Tijuana.
doi:10.7448/IAS.18.1.19304
PMCID: PMC4323407  PMID: 25669423
men who have sex with men; correlates of HIV infection; HIV prevalence; US–Mexico border; global public health; respondent-driven sampling
5.  Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis 
Introduction
HIV infections and the use of amphetamine-type stimulants (ATS) among men who have sex with men (MSM) have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM.
Methods
We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association – prevalence rate ratios (PRR, cross-sectional studies), odds ratio (OR, case-control studies) and hazard ratio (HR, longitudinal studies), with 95% Confidence Intervals (CI) – were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy). We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis.
Results
We identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35) were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR=1.86; 95% CI: 1.57–2.17; OR=2.73; 95% CI: 2.16–3.46 and HR=3.43; 95% CI: 2.98–3.95, respectively, for cross-sectional, case-control and longitudinal studies). Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR=1.15; 95% CI: 0.88–1.49; OR=3.04; 95% CI: 1.29–7.18 and HR=2.48; 95% CI: 1.42–4.35, respectively, for cross-sectional, case-control and longitudinal studies). Results in cross-sectional studies were highly heterogeneous due to issues with ATS measurement and different sampling frames.
Conclusions
While meth/amphetamine use was significantly associated with HIV infection among MSM in high-income countries in all study designs, evidence of the role of ecstasy in HIV infection was lacking in cross-sectional studies. Cross-sectional study design, measurement approaches and source populations may also be important modifiers of the strength and the direction of associations. Event-specific measure of individual drug is required to establish temporal relationship between ATS use and HIV infection. HIV prevention programmes targeting MSM should consider including interventions designed to address meth/amphetamine use.
doi:10.7448/IAS.18.1.19273
PMCID: PMC4302169  PMID: 25609214
HIV; amphetamine-type stimulants; MSM; systematic review; meta-analysis; risk behaviour; meth/amphetamine; ecstasy
7.  Community-academic partnerships in HIV-related research: a systematic literature review of theory and practice 
Introduction
Community involvement in HIV research has increased over recent years, enhancing community-academic partnerships. Several terms have been used to describe community participation in research. Clarification is needed to determine whether these terms are synonymous or actually describe different research processes. In addition, it remains unclear if the role that communities play in the actual research process follows the recommendations given in theoretical frameworks of community-academia research.
Objectives
The objective of this study is to review the existing terms and definitions regarding community-academic partnerships and assess how studies are implementing these in relation to conceptual definitions.
Methods
A systematic literature review was conducted in PubMed. Two reviewers independently assessed each article, applying the following inclusion criteria: the article must be published in English before 2013; it must provide an explicit definition and/or defining methodology for a term describing research with a community component; and it has to refer to HIV or AIDS, reproductive health and/or STDs. When disagreements about the relevance of an article emerged, a third reviewer was involved until concordance was reached. Data were extracted by one reviewer and independently verified by a second. Qualitative data were analyzed using MaxQDA for content and thematic analyses while quantitative data were analyzed using descriptive statistics. Community feedback on data analysis and presentation of results was also incorporated.
Results
In total, 246 articles were retrieved, 159 of which fulfilled the inclusion criteria. The number of studies that included community participation in the field of HIV research increased between 1991 and 2012, and the terms used to describe these activities have changed, moving away from action research (AR) to participatory action research (PAR), community-based research (CBR) and community-based participatory research (CBPR), with the latter being the most commonly used term. While definitions of all terms had common characteristics (e.g. participation of community in research process), they varied with regard to the emphasis placed on these characteristics. The nature of community participation in reviewed studies differed considerably from that described in theoretical models.
Conclusions
This study indicates the increase of participatory approaches in HIV research and underlines the need for clarification of terms and a framework providing orientation to community-academia partnerships.
doi:10.7448/IAS.18.1.19354
PMCID: PMC4309828  PMID: 25630823
HIV; action research; participatory action research; community-based research; community-based participatory research; community involvement; literature review
8.  Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin-positive compartments that are accessible to broadly neutralizing antibodies 
Introduction
Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been shown to be infected in vivo and sustain low levels of viral replication in vitro; however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined. The objective of this study is to define potential sites of viral assembly, accumulation and neutralization in HCs given the pivotal role of the placenta in preventing HIV-1 infection in the mother-infant dyad.
Methods
Term placentae from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated by 3D confocal and electron microscopy. Colocalization R values (Pearson's correlation) were quantified with colocalization module of Volocity 5.2.1. Replication kinetics and neutralization studies were evaluated using p24 ELISA.
Results
We demonstrate that primary HCs assemble and sequester HIV-1BaL in intracellular VCCs, which are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP-1. Following infection, we observed HIV-1 accumulation in potentially acidic compartments, which stained intensely with Lysotracker-Red. Remarkably, these compartments are readily accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1-specific broadly neutralizing antibodies. In addition, broadly neutralizing antibodies (4E10 and VRC01) limited viral replication by HIV-1-infected HCs, which may be mediated by FcγRI.
Conclusions
These findings suggest that placental HCs possess intrinsic adaptations facilitating unique sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral neutralization and/or antiretroviral drug entry in utero.
doi:10.7448/IAS.18.1.19385
PMCID: PMC4308659  PMID: 25623930
placenta; Hofbauer cells; HIV-1; VCCs; bNAbs; MTCT
10.  HIV/AIDS and lipodystrophy: Implications for clinical management in resource-limited settings 
Introduction
Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings.
Methods
We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n=799), 90 studies were included in this review.
Results and Discussion
Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden.
Conclusions
Lipodystrophy is common in resource-limited settings, and has considerable implications for risk of metabolic diseases, quality of life and adherence. Comprehensive evidence-based interventions are urgently needed to reduce the burden of HIV and lipodystrophy, and inform clinical management in resource-limited settings.
doi:10.7448/IAS.18.1.19033
PMCID: PMC4297925  PMID: 25598476
HIV; AIDS; lipodystrophy; fat redistribution; antiretroviral therapy
11.  Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe, Malawi 
Background
Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.
Methods
Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007–February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008–February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009–February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.
Results
During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5–70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p<0.001).
During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.
Conclusions
A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.
doi:10.7448/IAS.18.1.19305
PMCID: PMC4287633  PMID: 25571857
case finding; linkage to care; children; HIV; paediatrics; Africa; community health workers; HIV-exposed infants
12.  Risk factors for HIV infection among circumcised men in Uganda: a case-control study 
Introduction
Male circumcision (MC) reduces the risk of HIV infection. However, the risk reduction effect of MC can be modified by type of circumcision (medical, traditional and religious) and sexual risk behaviours post-circumcision. Understanding the risk behaviours associated with HIV infection among circumcised men (regardless of form of circumcision) is critical to the design of comprehensive risk reduction interventions. This study assessed risk factors for HIV infection among men circumcised through various circumcision approaches.
Methods
This was a case-control study which enrolled 155 cases (HIV-infected) and 155 controls (HIV-uninfected), all of whom were men aged 18–35 years presenting at the AIDS Information Center for HIV testing and care. The outcome variable was HIV sero-status. Using SPSS version 17, multivariable logistic regression was performed to identify factors independently associated with HIV infection.
Results
Overall, 83.9% among cases and 56.8% among controls were traditionally circumcised; 7.7% of cases and 21.3% of controls were religiously circumcised while 8.4% of cases and 21.9% of controls were medically circumcised. A higher proportion of cases than controls reported resuming sexual intercourse before complete wound healing (36.9% vs. 14.1%; p<0.01). Risk factors for HIV infection prior to circumcision were:being in a polygamous marriage (AOR: 6.6, CI: 2.3–18.8) and belonging to the Bagisu ethnic group (AOR: 6.1, CI: 2.6–14.0). After circumcision, HIV infection was associated with: being circumcised at >18 years (AOR: 5.0, CI: 2.4–10.2); resuming sexual intercourse before wound healing (AOR: 3.4, CI: 1.6–7.3); inconsistent use of condoms (AOR: 2.7, CI: 1.5–5.1); and having sexual intercourse under the influence of peers (AOR: 2.9, CI: 1.5–5.5). Men who had religious circumcision were less likely to have HIV infection (AOR: 0.4, 95% CI: 0.2–0.9) than the traditionally circumcised but there was no statistically significant difference between those who were traditionally circumcised and those who were medically circumcised (AOR: 0.40, 95% CI: 0.1–1.1).
Conclusions
Being circumcised at adulthood, resumption of sexual intercourse before wound healing, inconsistent condom use and having sex under the influence of peers were significant risk factors for HIV infection. Risk reduction messages should address these risk factors, especially among traditionally circumcised men.
doi:10.7448/IAS.18.1.19312
PMCID: PMC4283027  PMID: 25556374
HIV risk behaviours; male circumcision; risk factors for HIV infection; Uganda; case-control study
13.  Preparatory behaviours and condom use during receptive and insertive anal sex among male-to-female transgenders (Waria) in Jakarta, Indonesia 
Introduction
The male-to-female transgender (waria) is part of a key population at higher risk for HIV. This study aims to test whether psychosocial determinants as defined by the theory of planned behaviour (TPB) can explain behaviours related to condom use among waria. Three preparatory behaviours (getting, carrying, and offering a condom) and two condom use behaviours (during receptive and insertive anal sex) were assessed.
Methods
The study involved 209 waria, recruited from five districts in Jakarta and interviewed by using structured questionnaires. Specific measures were developed to study attitudes, subjective norms and perceived behavioural control (PBC) in order to predict intentions and behaviours.
Results
The explained variance between intentions with regard to three preparatory behaviours and two condom uses ranged between 30 and 57%, and the variance between the actual preparatory behaviours of three preparatory and two condom uses ranged between 21 and 42%. In our study, as with several previous studies of the TPB on HIV protection behaviours, the TPB variables differed in their predictive power. With regard to intention, attitude and PBC were consistently significant predictors; attitude was the strongest predictor of intention for all three preparatory behaviours, and PBC was the strongest predictor of intention for condom use, both during receptive and insertive anal sex. TPB variables were also significantly related to the second parameter of future behaviour: actual (past) behaviour. TPB variables were differentially related to the five behaviours. Attitude was predictive in three behaviours, PBC in three behaviours and subjective norms in two behaviours.
Conclusions
Our results have implications for the development of interventions to target preparatory behaviours and condom use behaviours. Five behaviours and three psychological factors as defined in the TPB are to be targeted.
doi:10.7448/IAS.17.1.19343
PMCID: PMC4273177  PMID: 25529498
transgender; theory of planned behaviour; preparatory behaviours; condom use; HIV/AIDS; Indonesia
14.  Antiretroviral treatment outcome in HIV-1-infected patients routinely followed up in capital cities and remote areas of Senegal, Mali and Guinea-Conakry 
Introduction
Access to antiretroviral treatment (ART) becomes more and more effective in resource-limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV-1 drug resistance in three West African countries using dried blood spots (DBS) samples.
Methods
We included HIV-1-infected adults on ART ≥6 months and followed up in capital cities and decentralized sites in Senegal, Mali and Guinea-Conakry. Patients were consecutively enrolled and DBS were collected in field conditions and kept at ambient temperature before transfer to the reference laboratory. Viral load (VL) was quantified using the NucliSENS EasyQ HIV-1 v1.2. Genotyping of HIV-1 pol gene was performed using in-house protocol.
Results
Of the 407 participants, 119, 152 and 136 were from Senegal, Mali and Guinea-Conakry, respectively. The median treatment duration was 36 months [IQR: 6–136]. Virological failure (VF) (VL≥3log10 copies/mL) was observed in 26% (95% confidence interval (CI), 18–35; n=31), 11% (95% CI, 6–17; n=16) and 24% (95% CI, 17–32; n=33) of patients in Senegal, Mali and Guinea-Conakry, respectively (p=0.001). Of samples presenting VL≥3log10 copies/mL (n=80), 70 were successfully genotyped. At least one drug resistance mutation (DRM) was detected in the following proportions: 70% (95% CI, 50–86; n=19), 93% (95% CI, 68–100; n=14) and 68% (95% CI, 48–84; n=19) in Senegal, Mali and Guinea-Conakry, respectively (p=0.22). Twenty-six per cent (26%; 95% CI, 16–38; n=18) of patients in VF harboured wild-type viruses, which is likely indicative of weak adherence. Phylogenetic analysis showed the predominance of CRF02_AG subtype (73%; 95% CI, 61–83; n=51).
Conclusions
We describe the ART outcome in capital and rural settings of Senegal, Mali and Guinea-Conakry. Our results in all of the three countries highlight the need to reinforce the ART adherence in order to minimize the occurrence of drug resistance. In addition, these findings provide additional evidence that the use of DBS as a sampling support could assist virological monitoring of patients on ART in remote areas.
doi:10.7448/IAS.17.1.19315
PMCID: PMC4272405  PMID: 25527333
HIV-1 drug resistance; viral load; HIV-1 genetic diversity; dried blood spots; remote areas; West Africa
15.  Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration 
Introduction
HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe such capacity in HIV programmes in seven regions worldwide.
Methods
Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed a site survey from 2009 to 2010, including sites in the Asia-Pacific region (n=20), Latin America and the Caribbean (n=7), North America (n=7), Central Africa (n=12), East Africa (n=51), Southern Africa (n=16) and West Africa (n=15). We computed a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services.
Results
Most sites reported serving urban (61%; region range (rr): 33–100%) and both adult and paediatric populations (77%; rr: 29–96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential services, survey respondents reported that CD4+ cell count testing was available to all but one site, while tuberculosis (TB) screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services – nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child transmission (PMTCT) (94%) and other prevention and clinical management services (97%) – were uniformly available. Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the UN Human Development Index (HDI), especially those in the President's Emergency Plan for AIDS Relief focus countries, tended to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied according to the number of years the site had been in operation and the HDI of the site setting, with more recently established clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the provision of isoniazid preventive therapy as unavailable services.
Conclusions
This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care.
doi:10.7448/IAS.17.1.19045
PMCID: PMC4268491  PMID: 25516092
HIV/AIDS; HIV care capacity; clinic characteristics; comprehensive care; resource-limited settings
16.  Addressing gender inequality and intimate partner violence as critical barriers to an effective HIV response in sub-Saharan Africa 
Introduction
In Africa, women and girls represent 57% of people living with HIV, with gender inequality and violence being an important structural determinant of their vulnerability. This commentary draws out lessons for a more effective combination response to the HIV epidemic from three papers recently published in JIAS.
Discussion
Hatcher and colleagues present qualitative data from women attending ante-natal clinics in Johannesburg, describing how HIV diagnosis during pregnancy and subsequent partner disclosure are common triggers for violence within relationships. The authors describe the challenges women face in adhering to medication or using services. Kyegombe and colleagues present a secondary analysis of a randomized controlled trial in Uganda of SASA! – a community violence prevention programme. Along with promising community impacts on physical partner violence, significantly lower levels of sexual concurrency, condom use and HIV testing were reported by men in intervention communities. Remme and her colleagues present a systematic review of evidence on the costs and cost-effectiveness of gender-responsive HIV interventions. The review identified an ever-growing evidence base, but a paucity of accompanying economic analyses, making it difficult to assess the costs or value for money of gender-focused programmes.
Conclusions
There is a need to continue to accumulate evidence on the effectiveness and costs of different approaches to addressing gender inequality and violence as part of a combination HIV response. A clearer HIV-specific and broader synergistic vision of financing and programming needs to be developed, to ensure that the potential synergies between HIV-specific and broader gender-focused development investments can be used to best effect to address vulnerability of women and girls to both violence and HIV.
doi:10.7448/IAS.17.1.19849
PMCID: PMC4265114  PMID: 25499456
gender inequality; intimate partner violence; interventions; sub-Saharan Africa
17.  Incidence and mortality of tuberculosis before and after initiation of antiretroviral therapy: an HIV cohort study in India 
Introduction
India has the highest burden of tuberculosis (TB) in the world, but the epidemiology of HIV-associated TB is not well known.
Methods
We describe the incidence and the mortality of TB from HIV diagnosis to antiretroviral therapy (ART) initiation (pre-ART group) and after ART initiation (on-ART group) in an HIV cohort study in Anantapur, India. Multivariable analysis of factors associated with TB was performed using competing risk regression and restricted cubic spline methods.
Results
A total of 4590 patients and 3133 person-years (py) of follow-up were included in the pre-ART group, and 3784 patients and 4756 py were included in the on-ART group. In the pre-ART group, the incidence of TB was high during the first month after HIV diagnosis and dropped nearly four times soon after. In the on-ART group, the incidence of TB increased after ART initiation reaching a peak in the third month. The probability of having TB within 30 months was 22.3% (95% confidence interval [CI], 21.1–23.6) in the pre-ART group and 17.8% (95% CI, 16.3–19.3) in the on-ART group. In a multivariable analysis, women had a lower risk of TB in both groups. Poor socio-economical conditions were associated with an increased risk of TB in the pre-ART group, but not in the group on-ART. While the association between low CD4 counts and TB was strong in the pre-ART group, this association was weaker in the on-ART group, and the highest risk of TB was seen in those patients with CD4 counts around 110 cells/mm3. The cumulative incidence of mortality at 12 months in patients with TB was 29.6% (95% CI, 26.9–32.6) in pre-ART TB and 34.9% (95% CI, 31–39.1) in on-ART TB. Half deaths before ART initiation and two thirds of deaths after ART initiation occurred in patients with TB.
Conclusions
The high incidence and mortality of TB seen in this study underscore the urgent need to improve the prevention and diagnosis of HIV-associated TB in India. We found substantial differences between TB before and after ART initiation.
doi:10.7448/IAS.17.1.19251
PMCID: PMC4262765  PMID: 25499123
HIV; tuberculosis; mortality; incidence; India; rural; antiretroviral therapy; gender; CD4 lymphocyte count; risk
18.  Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study 
Introduction
Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR.
Methods
We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50–90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.
Results
The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2–7.2%) in 2014, to 6.8% (IQR 6.1–7.6%), 10.0% (IQR 8.9–11.5%) and 11.1% (IQR 9.7–13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4–8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1–10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from $1612 to $2234 (IQR $450-dominated) per QALY gained.
Conclusions
While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority.
doi:10.7448/IAS.17.1.19164
PMCID: PMC4260459  PMID: 25491351
drug resistance; second-line treatment; pre-therapy genotyping; viral load monitoring; cost-effectiveness; antiretroviral therapy
19.  What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers 
Introduction
Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda.
Methods
We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation.
Results
The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans’ caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers.
Conclusions
Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.
doi:10.7448/IAS.17.1.19310
PMCID: PMC4256520  PMID: 25477050
HIV; AIDS; ART adherence; antiretroviral therapy; orphan; child; Rwanda; sub-Saharan Africa
20.  HIV and Ebola: similarities and differences 
doi:10.7448/IAS.17.1.19896
PMCID: PMC4252165  PMID: 25466882
21.  Measuring adherence to antiretroviral therapy in children and adolescents in western Kenya 
Introduction
High levels of adherence to antiretroviral therapy (ART) are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV-infected children in western Kenya.
Methods
We evaluated ART adherence prospectively for six months among HIV-infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS®). Kappa statistics were used to compare adherence estimates with MEMS®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS® adherence ≥90% vs. <90%) and MEMS® treatment interruptions of ≥48 hours. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
Results
Among 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS® was 96.3% and improved over the course of follow-up (p<0.01), although 49.5% of children had at least one MEMS® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS® and other adherence measures (Kappa statistics 0.04–0.37). In multivariable logistic regression, only caregiver-reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14–1.39), late doses in the past seven days (OR 1.14, 95% CI 1.05–1.22) and caregiver-reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01–1.20) were significantly associated with dichotomized MEMS® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01–1.25) and reporting difficulties in the community that made giving ART more difficult (e.g. stigma) (OR 1.14, 95% CI 1.02–1.27) were significantly associated with MEMS® treatment interruptions in multivariable logistic regression.
Conclusions
Non-adherence in the form of missed and late doses, treatment interruptions of more than 48 hours and sub-therapeutic drug levels were common in this cohort. Adherence varied significantly by adherence measure, suggesting that additional validation of adherence measures is needed. Few factors were consistently associated with non-adherence or treatment interruptions.
doi:10.7448/IAS.17.1.19227
PMCID: PMC4245448  PMID: 25427633
adherence; paediatric HIV; best practice; resource-limited setting
24.  HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya 
Introduction
Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information.
Methods
We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS–USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveSTTM-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance.
Results
Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS.
Conclusions
In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.
doi:10.7448/IAS.17.1.19262
PMCID: PMC4238965  PMID: 25413893
HIV; drug resistance; subtype; diversity; Kenya; analyte; AMPATH
25.  Low adverse event rates following voluntary medical male circumcision in a high HIV disease burden public sector prevention programme in South Africa 
Introduction
The provision of voluntary medical male circumcision (VMMC) services was piloted in three public sector facilities in a high HIV disease burden, low circumcision rate province in South Africa to inform policy and operational guidance for scale-up of the service for HIV prevention. We report on adverse events (AEs) experienced by clients following the circumcision procedure.
Methods
Prospective recruitment of HIV-negative males aged 12 and older volunteering to be circumcised at three select public health facilities in KwaZulu-Natal between November 2010 and May 2011. Volunteers underwent standardized medical screening including a physical assessment prior to the surgical procedure being performed. AEs were monitored at three time intervals over a 21-day period post-operatively to determine safety outcomes in this pilot demonstration programme.
Results
A total of 602 volunteers participated in this study. The median age of the volunteers was 22 years (range 12–56). Most participants (75.6%) returned for the 48-hour post-operative visit; 51.0% for day seven visit and 26.1% for the 21st day visit. Participants aged 20–24 were most likely to return. The AE rate was 0.2% intra-operatively. The frequency of moderate AEs was 0.7, 0.3 and 0.6% at 2-, 7- and 21-day visits, respectively. The frequency of severe AEs was 0.4, 0.3 and 0.6% at 2-, 7- and 21-day visits, respectively. Swelling and wound infection were the most common AEs with mean appearance duration of seven days. Clients aged between 35 and 56 years presented with most AEs (3.0%).
Conclusions
VMMC can be delivered safely at resource-limited settings. The intensive three-visit post-operative review practice may be unfeasible due to high attrition rates over time, particularly amongst older men.
doi:10.7448/IAS.17.1.19275
PMCID: PMC4236629  PMID: 25406951
medical male circumcision; HIV prevention; adverse events; follow-up visit

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