The impact of SASA!, a community mobilization intervention,on reported HIV-related risk behaviours and relationship dynamics in Kampala,Uganda

Introduction

Intimate partner violence (IPV) violates women''s human rights, and it is a serious public health concern associated with increased HIV risk. SASA!, a phased community mobilization intervention, engages communities to prevent IPV and promote gender equity. The SASA! study assessed the community-level impact of SASA! on reported HIV-related risk behaviours and relationship dynamics.

Methods

Data were collected as part of a cluster randomized controlled trial conducted between 2007 and 2012 in eight communities in Kampala. An adjusted cluster-level intention to treat analysis, compares secondary outcomes in intervention and control communities at follow-up. The qualitative evaluation explored participants’ subjective experience of SASA!. A total of 82 in-depth interviews were audio recorded at follow-up, transcribed verbatim and analyzed using thematic analysis.

Results

Men in intervention communities were significantly more likely than controls to report a broad range of HIV-protective behaviours, including higher levels of condom use (aRR 2.03, 95% CI 1.22–3.39), HIV testing (aRR 1.50, 95% CI 1.13–2.00) and fewer concurrent partners (aRR 0.60, 95% CI 0.37–0.97). They were also more likely to report increased joint decision-making (aRR 1.92, 95% CI 1.27–2.91), greater male participation in household tasks (aRR 1.48, 95% CI 1.09–2.01), more open communication and greater appreciation of their partner''s work inside (aRR 1.31, 95% CI 1.04–1.66) and outside (aRR 1.49, 95% CI 1.08–2.06) the home. For women, all outcomes were in the hypothesized direction, but effect sizes were smaller. Only some achieved statistical significance. Women in intervention communities were significantly more likely to report being able to refuse sex with their partners (aRR 1.16, 95% CI 1.00–1.35), joint decision-making (aRR 1.37, 95% CI 1.06–1.78) and more open communication on a number of indicators. Qualitative interviews suggest that shifts operated through broader improvements in relationships, including increased trust and cooperation, participants’ greater awareness of the connections between HIV and IPV and their resultant desire to improve their relationships. Barriers to change include partial uptake of SASA!, partner resistance, fear and entrenched previous beliefs.

Conclusions

SASA! impacted positively on reported HIV-related risk behaviours and relationship dynamics at a community level, especially among men. Social change programmes focusing on IPV and gender equity could play an important role in HIV prevention efforts.     

Poor CD4 recovery and risk of subsequent progression to AIDS or death despite viral suppression in a South African cohort

Introduction

The prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear.

Methods

This was a cohort study of HIV-positive adults initiating antiretroviral therapy (ART) between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml) by six months on treatment in South Africa. Immunological response at six months was defined as: (1) absolute CD4 reached (<200 vs. ≥200 cells/ml); (2) absolute CD4 reached (0–49, 50–200 and ≥200 cells/ml); and (3) CD4 increase from ART initiation (<0, 0–49, 50–199 and ≥200 cells/ml). We used Cox regression models to determine the relationship between each definition and both new AIDS-defining condition and death.

Results

A total of 4129 patients were eligible for analysis; 212 (5.1%) of those patients experienced a new AIDS-defining condition and 154 (3.7%) died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥200 cells/ml; adjusted hazard ratio (aHR): 2.6; 95% CI: 1.2–2.1) and death (aHR: 2.8; 95% CI: 1.4–5.7). A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2–4.9) and smaller CD4 count gains (0–49 cells/ml; aHR: 2.0; 95% CI: 1.2–3.4 and 50–199 cells/ml; aHR: 1.5; 95% CI: 0.9–2.2) were also associated with greater risk of progression to AIDS compared to an increase of ≥200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98–1.95.

Conclusions

Patients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub-group of patients need further investigation.     

Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy

Introduction

Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART.

Methods

This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models.

Results

In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64–0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58–0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02–1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05–1.21; p<0.001).

Conclusions

A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.     

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.     

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau – a retrospective cohort study

Introduction

With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau.

Methods

In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up.

Results

We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).

Conclusions

We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.     

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.     

People living with HIV travel farther to access healthcare: a population-based geographic analysis from rural Uganda

Introduction

The availability of specialized HIV services is limited in rural areas of sub-Saharan Africa where the need is the greatest. Where HIV services are available, people living with HIV (PLHIV) must overcome large geographic, economic and social barriers to access healthcare. The objective of this study was to understand the unique barriers PLHIV face when accessing healthcare compared with those not living with HIV in a rural area of sub-Saharan Africa with limited availability of healthcare infrastructure.

Methods

We conducted a population-based cross-sectional study of 447 heads of household on Bugala Island, Uganda. Multiple linear regression models were used to compare travel time, cost and distance to access healthcare, and log binomial models were used to test for associations between HIV status and access to nearby health services.

Results

PLHIV travelled an additional 1.9 km (95% CI (0.6, 3.2 km), p=0.004) to access healthcare compared with those not living with HIV, and they were 56% less likely to access healthcare at the nearest health facility to their residence, so long as that facility lacked antiretroviral therapy (ART) services (aRR=0.44, 95% CI (0.24 to 0.83), p=0.011). We found no evidence that PLHIV travelled further for care if the nearest facility supplies ART services (aRR=0.95, 95% CI (0.86 to 1.05), p=0.328). Among those who reported uptake of care at one of two facilities on the island that provides ART (81% of PLHIV and 68% of HIV-negative individuals), PLHIV tended to seek care at a higher tiered facility that provides ART, even when this facility was not their closest facility (30% of PLHIV travelled further than the closest ART facility compared with 16% of HIV-negative individuals), and travelled an additional 2.2 km (p=0.001) to access that facility, relative to HIV-negative individuals (aRR=1.91, 95% CI (1.00 to 3.65), p=0.05). Among PLHIV, residential distance was associated with access to facilities providing ART (RR=0.78, 95% CI (0.61 to 0.99), p=0.044, comparing residential distances of 3–5 km to 0–2 km; RR=0.71, 95% CI (0.58 to 0.87), p=0.001, comparing residential distances of 6–10 km to 0–2 km).

Conclusions

PLHIV travel longer distances for care, a phenomenon that may be driven by both the limited availability of specialized HIV services and preference for higher tiered facilities.     

The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso

Introduction

Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso.

Methods

We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART.

Results

Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77–3.60; p<0.001).

Conclusions

Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to determine the causes for their vulnerability in order to optimize HIV care. From now on, efforts should be made to support the adherence of men to ART in the African setting.     

Lopinavir/r no longer recommended as a first-line regimen: a comparative effectiveness analysis

Introduction

We compared the effectiveness of tenofovir/emtricitabine (TDF/FTC) combined with either lopinavir/r (LPV/r) or another recommended third drug in the 2010 French guidelines in antiretroviral-naïve patients starting combination antiretroviral therapy in 2004–2008 in the French Hospital Database on HIV.

Methods

The outcomes were stop or switch of the third component, viral load (VL) <500 copies/ml, an increase of at least 100 CD4 cells/mm³, AIDS-defining event and non-AIDS-defining hospitalization or death. Propensity scores were estimated by logistic regression based on the clinical centre and other confounders. In each clinical centre, each patient initiating LPV/r was matched with a patient initiating another third drug (efavirenz or atazanavir/r) and having a close propensity score. Cox''s proportional hazards models were then used, with treatment as covariate. Time was right-censored at four years.

Results

1269 patients started LPV/r plus TDF/FTC, and 890 could be matched to 890 patients receiving another third drug. Baseline characteristics were well balanced between these two groups. LPV/r was associated with a higher risk of third drug stop (hazard ratio (HR): 1.69; 95% confidence interval (CI), 1.42–2.00) and with less rapid viral suppression (HR: 0.83; 95% CI, 0.72–0.95). There was no difference in the time required for a CD4 cell increment of at least 100/mm³, or to the occurrence of an AIDS-defining event. Non-AIDS-defining hospitalizations or deaths were more frequent with LPV/r (HR: 1.79; 95% CI, 1.33–2.39).

Conclusions

For first-line therapy, in this observational setting, TDF/FTC plus LPV/r were less durable than TDF/FTC plus another recommended third drug, led to a less rapid viral suppression and were associated with a higher risk of non-AIDS morbidity.     

Not all total joint replacement patients are created equal: preoperative factors and length of stay in hospital

Background

We conducted a cross-sectional study of primary total joint replacement (TJR) patients to determine predictors for prolonged length of stay (LOS) in hospital to identify patient characteristics that may inform resource allocation, accounting for patient complexity.

Methods

Preoperative demographics, medical comorbidities and acute hospital LOS from a consecutive series of primary TJR patients from an academic arthroplasty centre were abstracted. We categorized patients as LOS of 3 or fewer days, 4 days, or 5 or more days to align results with varying LOS benchmarks. To identify predictors for LOS, we used a generalized logistic regression model fitted on an LOS ternary outcome, using LOS of 3 or fewer days as a reference category.

Results

The sample included 1459 patients: 61.7% total knee and 38.3% total hip. Male sex was predictive of an LOS of 3 or fewer days (4 d: odds ratio [OR] 0.48, 95% confidence interval [CI] 0.364–0.631; ≥ 5 d: OR 0.57, 95% CI 0.435–0.758), as was current smoking status (4 d: OR 0.425, 95% CI 0.274–0.659; ≥ 5 d: OR 0.489, 95% CI 0.314–0.762). Strong predictors of prolonged LOS included total hip versus total knee arthroplasty, age 75 years or older, American Society of Anesthesiologists classification of 3 and 4 and number of cardiovascular comorbidities.

Conclusion

Not all patients undergoing TJR are equal. The goal should be individual patient-focused care rather than a predetermined LOS that is not achievable for all patients. Hospital resource planning must account for patient complexity when planning future bed management.     

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique

Introduction

Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well-characterized.

Methods

We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005–2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites.

Results

Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345–611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2–41.8) and 48% (95% CI: 47.2–48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHR_{men_vs_non-pregnant women}: 1.5; 95% CI: 1.4–1.6) and being pregnant at enrolment (AHR_{pregnant_vs_non-pregnant women}: 1.3; 95% CI: 1.1–1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment.

Conclusions

Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease.     

Correlates of HIV infection and being unaware of HIV status among soon-to-be-released Ukrainian prisoners

Introduction

Prisoners bear a disproportionate burden of Ukraine''s volatile and transitional HIV epidemic, yet little is known in Eastern Europe about HIV testing, treatment and HIV-related risk among prisoners.

Methods

A nationally representative biobehavioural health survey linked with serological testing was conducted among soon-to-be released prisoners in 13 Ukrainian prisons from June to November 2011.

Results

Among 402 participants, 78 (19.4%) tested HIV seropositive of whom 38 (50.7%) were previously unaware of their HIV status. Independent correlates of HIV infection included drug injection (AOR=4.26; 95% CI: 2.23–8.15), female gender (AOR=2.00; 95% CI: 1.06–3.78), previous incarceration (AOR=1.99; 95% CI: 1.07–3.70) and being from Southern Ukraine (AOR=5.46; 95% CI: 2.21–13.46). Those aware of being HIV-positive reported significantly more pre-incarceration sex- and drug-related HIV risk behaviours than those who were unaware.

Conclusions

Routine rather than risk-based HIV testing and expansion of opioid substitution and antiretroviral therapy among prisoners is urgently needed to reduce HIV transmission in volatile transitional HIV epidemics.     

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

Introduction

Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho.

Methods

The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender.

Results

Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73–1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93).

Conclusions

In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals.     

Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

Introduction

Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

Methods

Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm³ or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

Results

A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm³. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm³ in 2008 to a peak of 302 cells/mm³ after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).

Conclusions

Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.     

CD4 criteria improves the sensitivity of a clinical algorithm developed to identify viral failure in HIV-positive patients on antiretroviral therapy

Introduction

Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.

Methods

We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤400 copies/ml. We used Cox-proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria (CD4 <100 cells/mm³; CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure.

Results

We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mm³, WHO stage III/IV and albumin) and laboratory and clinical follow-up data (drop in haemoglobin, mean cell volume (MCV) <100 fl, CD4 count <200 cells/mm³, new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score 51.4% had a score ≥4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico-immunological criteria or WHO clinical staging to predict virologic failure (sensitivity 57.1% vs. 40.9%, 25.2% and 20.9%, respectively).

Conclusions

Predictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes.     

Exposing the gaps in awareness,knowledge and estimation of risk for anal cancer in men who have sex with men living with HIV: a cross-sectional survey in Australia

Introduction

The incidence of anal cancer is significantly higher in men who have sex with men (MSM) living with HIV when compared to the general population. We aimed to assess their awareness, knowledge and perceived level of personal risk for anal cancer to help inform educational strategies targeting this group.

Methods

A cross-sectional study of 327 HIV positive MSM in Melbourne, Australia, attending clinical settings (a sexual health centre, tertiary hospital HIV outpatients and high HIV caseload general practices) completed a written questionnaire in 2013/14. Poor knowledge was defined as those who had never heard of anal cancer, or scored 5 or less out of 10 in knowledge questions amongst those who reported ever hearing about anal cancer. Underestimation of risk was defined as considering themselves as having the same or lower risk for anal cancer compared to the general population.

Results

Of 72% (95% confidence interval (CI): 67–77) who had heard of anal cancer, 47% (95% CI: 41–53) could not identify any risk factors for anal cancer. Of total men surveyed, 51% (95% CI: 46–57) underestimated their risk for anal cancer. Multivariate analysis showed that men who underestimated their risk were older (OR 1.04 (per year increase in age), 95% CI: 1.01–1.07), had poor anal cancer knowledge (OR 2.06, 95% CI: 1.21–3.51), and more likely to have ever had an anal examination (OR 2.41, 95% CI: 1.18–4.93). They were less likely to consult a physician if they had an anal abnormality (OR 0.54, 95% CI: 0.31–0.96), to have had receptive anal sex (OR 0.12, 95% CI: 0.02–0.59) or speak English at home (OR 0.28, 95% CI: 0.09–0.90).

Conclusions

This survey of MSM living with HIV demonstrated limited awareness, knowledge level and estimation of risk for anal cancer. Further educational and public health initiatives are urgently needed to improve knowledge and understanding of anal cancer risk in MSM living with HIV.     

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.