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.     

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.     

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.     

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.     

Towards elimination of mother-to-child transmission of HIV: performance of different models of care for initiating lifelong antiretroviral therapy for pregnant women in Malawi (Option B+)

Introduction

Malawi introduced a new strategy to improve the effectiveness of prevention of mother-to-child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the “model of care”) and (ii) explore associations between the “model of care” and health facility–level uptake and retention rates for pregnant women identified as HIV-positive at antenatal (ANC) clinics.

Methods

A health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi''s 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports.

Results

Among 141 health facilities, four “models of care” were identified: A) facilities where newly identified HIV-positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV-positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow-up; C) facilities where newly identified HIV-positive women are referred from ANC to the ART clinic for initiation and follow-up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the “model of care” applied; factors independently associated with ART retention were district location, patient volume and the “model of care” applied.

Conclusions

A large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the “model of care” chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient-level research is needed to guide policy recommendations.     

Disengagement of HIV-positive pregnant and postpartum women from antiretroviral therapy services: a cohort study

Introduction

Recent international guidelines call for expanded access to triple-drug antiretroviral therapy (ART) in HIV-positive women during pregnancy and postpartum. However, high levels of non-adherence and/or disengagement from care may attenuate the benefits of ART for HIV transmission and maternal health. We examined the frequency and predictors of disengagement from care among women initiating ART during pregnancy in Cape Town, South Africa.

Methods

We used routine medical records to follow-up pregnant women initiating ART within prevention of mother-to-child transmission of HIV services in Cape Town, South Africa. Outcomes assessed through six months postpartum were (1) disengagement (no attendance within 56 days of a scheduled visit) and (2) missed visits (returning to care 14–56 days late for a scheduled visit).

Results

A total of 358 women (median age, 28 years; median gestational age, 26 weeks) initiated ART during pregnancy. By six months postpartum, 24% of women (n=86) had missed at least one visit and an additional 32% (n=115) had disengaged from care; together, 49% of women had either missed a visit or had disengaged by six months postpartum. Disengagement was more than twice as frequent postpartum compared to in the antenatal period (6.2 vs. 2.4 per 100 woman-months, respectively; p<0.0001). In a proportional hazards model, later gestational age at initiation (HR: 1.04; 95% CI: 1.00–1.07; p=0.030) and being newly diagnosed with HIV (HR: 1.57; 95% CI: 1.07–2.33; p=0.022) were significant predictors of disengagement after adjusting for patient age, starting CD4 cell count and site of ART initiation.

Conclusions

These results demonstrate that missed visits and disengagement from care occur frequently, particularly post-delivery, among HIV-positive women initiating ART during pregnancy. Women who are newly diagnosed with HIV may be particularly vulnerable and there is an urgent need for interventions both to promote retention overall, as well as targeting women newly diagnosed with HIV during pregnancy.     

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.     

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.     

Sexual risk after HIV diagnosis: a comparison of pre-ART individuals with CD4>500 cells/μl and ART-eligible individuals in a HIV treatment and care programme in rural KwaZulu-Natal,South Africa

Introduction

Little is known about people diagnosed as HIV-positive who access HIV care early in their disease. In pre-ART studies published to date, only a minority of the participants have CD4>500 cells/µl.

Methods

This cross-sectional study compared individuals presenting for HIV care with CD4>500 cells/µl, “pre-ART” (N=247), with individuals who had CD4<200 cells/µl or WHO Stage IV, “ART-eligible” (N=385). Baseline characteristics were contrasted between the two groups and logistic regression models used to explore group differences in: (a) being sexually active in the last month; (b) disclosure of HIV status to current partner; (c) knowing the HIV status of one''s current partner; and (d) condom use at last sex.

Results

Pre-ART and ART-eligible individuals were similar in terms of a wide range of socio-demographic characteristics. Controlling for gender, only current sexual behaviour and HIV-testing history were significantly different between ART groups. In multivariable models, participants in the pre-ART group were twice as likely to be sexually active in the last month, OR 2.06 95% CI (1.32, 3.21), and to know their partner''s status, OR 1.95 (1.18, 3.22) compared to those in the ART-eligible group. Self-reported disclosure of HIV status to current sexual partner (71%), condom use at last sex (61%) and HIV concordancy within relationships were not significantly different between the two ART groups. Overall, 39% of the study participants reported knowing that they were in concordant HIV-positive relationships. Fifty-five percent of all participants reported not knowing their partner''s HIV status, only half of whom reported using a condom at last sex. Pre-ART individuals were significantly less likely to have tested HIV-positive for the first time in the last year and to have tested for sickness-related reasons than the ART-eligible group.

Conclusions

Reported sexual risk behaviours by pre-ART individuals with CD4>500 cells/µl suggest a continued risk of onward HIV transmission. There is a need for positive prevention efforts to target this group given that current treatment guidelines do not provide them with ART. Strengthening support regarding disclosure, partner HIV testing and consistent condom use, and further promotion of HIV testing in the community to assist earlier diagnosis are urgently required.     

High-risk human papillomavirus infection in HIV-positive African women living in Europe

Introduction

Cervical infection with high-risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV-positive women living in Belgium.

Methods

Prospective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV-positive women between 2002 and 2011. Women without normal cervix at baseline were excluded.

Results

The final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow-up (66 months), median CD4 count (426 cells/μL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/μL and lowest (19%) in women >40 years and >500 CD4/μL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years-age increase and by 11% for each 100 CD4 cells/μL rise (RR=0.89, 95% CI: 0.85-0.93; p<0.0001, Poisson regression for both). During follow-up, incidence rate of HRHPV was 13.4 per 100 women-years.

Conclusions

We found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women-years in this cohort of HIV-positive women living in Europe and on cART. Women under 40 years-age had the highest prevalence even with CD4 count >350 cells/μL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV-infected women.     

Efficacy of WHO recommendation for continued breastfeeding and maternal cART for prevention of perinatal and postnatal HIV transmission in Zambia

Introduction

To prevent mother-to-child transmission (MTCT) of HIV in developing countries, new World Health Organization (WHO) guidelines recommend maternal combination antiretroviral therapy (cART) during pregnancy, throughout breastfeeding for 1 year and then cessation of breastfeeding (COB). The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated, but the efficacy of this approach beyond six months is not well documented.

Methods

A prospective observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter. Women were encouraged to exclusively breastfeed for six months, complementary feed for the next six months and then cease breastfeeding between 12 and 13 months. Infants were followed for transmission to 18 months and for survival to 24 months. Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up.

Results

Total MTCT was 9 of 219 live born infants (4.1%; confidence interval (CI) 2.2–7.6%). All breastfeeding transmissions that could be timed (5/5) occurred after six months of age. All mothers who transmitted after six months had a six-month plasma viral load >1,000 copies/ml (p<0.001). Poor adherence to cART as noted by missed dispensary visits was associated with transmission (p=0.04). Infant mortality was lower after six months of age than during the first six months of life (p=0.02). The cumulative rate of infant HIV infection or death at 18 months was 29/226 (12.8% 95 CI: 7.5–20.8%).

Conclusions

Maternal cART may limit MTCT of HIV to the UNAIDS target of <5% for eradication of paediatric HIV within the context of a clinical study, but poor adherence to cART and follow-up can limit the benefit. Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies, which encouraged early COB.     

Temporal trends of time to antiretroviral treatment initiation,interruption and modification: examination of patients diagnosed with advanced HIV in Australia

Introduction

HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART.

Methods

We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification.

Results

Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural–regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007–2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007–2012 versus 1996–2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV.

Conclusions

Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods.     

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care

Introduction

Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment.

Methods

Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm³ or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression.

Results

In total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm³ (Q1–Q3 80–320) in 2000 to 360 cells/mm³ (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm³ or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm³), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation.

Conclusions

This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.     

CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre

Objective

Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics.

Design

We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium.

Methods

We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?”

Results

Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naïve estimates depending on assumptions about access to care among lost patients.

Conclusions

Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it.     

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.     

Same‐day antiretroviral therapy (ART) initiation in pregnancy is not associated with viral suppression or engagement in care: A cohort study

Introduction

Many prevention of mother‐to‐child HIV transmission programmes across Africa initiate HIV‐infected (HIV positive) pregnant women on lifelong antiretroviral therapy (ART) on the first day of antenatal care (“same‐day” initiation). However, there are concerns that same‐day initiation may limit patient preparation before starting ART and contribute to subsequent non‐adherence, disengagement from care and raised viral load. We examined if same‐day initiation was associated with viral suppression and engagement in care during pregnancy.

Methods

Consecutive ART‐eligible pregnant women making their first antenatal care (ANC) visit at a primary care facility in Cape Town, South Africa were enrolled into a prospective cohort between March 2013 and June 2014. Before July 2013, ART eligibility was based on CD4 cell count ≤350 cells/μL (“Option A”), with a 1 to 2 week delay from the first ANC visit to ART initiation for patient preparation; thereafter all women were eligible regardless of CD4 cell count (“Option B+”) and offered ART on the same day as first ANC visit. Women were followed with viral load testing conducted separately from routine ART services, and engagement in ART services was measured using routinely collected clinic, pharmacy and laboratory records through 12 months postpartum.

Results

Among 628 HIV‐positive women (median age, 28 years; median gestation at ART start, 21 weeks; 55% newly diagnosed with HIV), 73% initiated ART same‐day; this proportion was higher under Option B+ versus Option A (85% vs. 20%). Levels of viral suppression (viral load <50 copies/mL) at delivery (74% vs. 82%) and 12 months postpartum (74% vs. 71%) were similar under same‐day versus delayed initiation respectively. Findings were consistent when viral suppression was defined at <1000 copies/mL, after adjustment for demographic/clinical measures and across subgroups of age, CD4 and timing of HIV diagnosis. Time to first viral rebound following initial suppression did not differ by timing of ART initiation nor did engagement in care through 12 months postpartum (same‐day = 73%, delayed = 73%, p = 0.910).

Conclusions

These data suggest that same‐day ART initiation during pregnancy is not associated with lower levels of engagement in care or viral suppression through 12 months post‐delivery in this setting, providing reassurance to ART programmes implementing Option B+.

     

Multivitamin supplementation improves haematologic status in children born to HIV-positive women in Tanzania

Introduction

Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality.

Objective

To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding.

Methods

A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations<11 g/dL and severe anaemia<8.5 g/dL.

Results

Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79–0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56–0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79–1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV.

Conclusions

Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy.