Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis

Introduction

Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple-drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates.

Materials and Methods

We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1) current ART and PMTCT coverage, 2) current ART and high PMTCT coverage, and 3) high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART) at current coverage.

Results

At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results.

Discussion

Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels) in Uganda than South Africa. These results are likely driven by Uganda’s higher fertility rates.     

Implementation of a Cloud-Based Electronic Medical Record to Reduce Gaps in the HIV Treatment Continuum in Rural Kenya

Background

Electronic medical record (EMR) systems are increasingly being adopted to support the delivery of health care in developing countries and their implementation can help to strengthen pathways of care and close gaps in the HIV treatment cascade by improving access to and use of data to inform clinical and public health decision-making.

Methods

This study implemented a novel cloud-based electronic medical record system in an HIV outpatient setting in Western Kenya and evaluated its impact on reducing gaps in the HIV treatment continuum including missing data and patient eligibility for ART. The impact of the system was assessed using a two-sample test of proportions pre- and post-implementation of EMR-based data verification and clinical decision support.

Results

Significant improvements in data quality and provision of clinical care were recorded through implementation of the EMR system, helping to ensure patients who are eligible for HIV treatment receive it early. A total of 2,169 and 764 patient records had missing data pre-implementation and post-implementation of EMR-based data verification and clinical decision support respectively. A total of 1,346 patients were eligible for ART, but not yet started on ART, pre-implementation compared to 270 patients pre-implementation.

Conclusion

EMR-based data verification and clinical decision support can reduce gaps in HIV care, including missing data and eligibility for ART. A cloud-based model of EMR implementation removes the need for local clinic infrastructure and has the potential to enhance data sharing at different levels of health care to inform clinical and public health decision-making. A number of issues, including data management and patient confidentiality, must be considered but significant improvements in data quality and provision of clinical care are recorded through implementation of this EMR model.     

A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

Background

It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.

Methods

People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.

Results

One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.

Conclusions

This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection.

Trial Registration

ClinicalTrials.gov NCT00106171     

Antiretroviral Therapy and Reasons for Not Taking It among Men Having Sex with Men (MSM)—Results from the European MSM Internet Survey (EMIS)

Background

The preventive effects of antiretroviral treatment (ART) on onward transmission of HIV are a major reason for broadening eligibility for ART. In the WHO European Region, surveillance reveals substantial differences in access to ART across regions and sub-populations. We analysed self-reported data on ART and reasons for not taking ART from EMIS, a large Pan-European Internet survey among men-who-have-sex-with-men (MSM).

Methods

Respondents from 38 European countries reported their last HIV test result and, if diagnosed with HIV, their treatment status, and reasons for not taking or having stopped ART from a 7 item multiple choice list and/ or answered an open-ended question to give other reasons. Responses were classified as fear of consequences, perceived lack of need, and ART inaccessibility based on factor analysis. Associations between not taking ART because of fear of consequences, and demographic, behavioural and contextual indicators were identified in a multivariable regression model.

Results

13,353 (7.7%) of 174,209 respondents had been diagnosed with HIV. Among them 3,391 (25.4%) had never received ART, and 278 (2.1%) had stopped taking ART. Perceived lack of need was by far the most common reason for not taking or stopping ART (mentioned by 3259 (88.8%) respondents), followed by fear of consequences (428 (11.7%)), and ART inaccessibility (86 (2.3%)). For all reasons, an East-West gradient could be seen, with larger proportions of men living in Central and Eastern Europe reporting reasons other than medical advice for not taking ART. A minority of men were reluctant to start ART independent of medical advice and this was associated with experiences of discrimination in health care systems.

Conclusions

ART is widely available for MSM diagnosed with HIV across Europe. Not being on treatment is predominantly due to treatment not being recommended by their physician and/or not perceived to be needed by the respondent.     

Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka,India: Two Year Follow-Up

Background

In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states.

Objectives

To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients.

Methods

Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011.

Results

A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome.

Conclusions

The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment.     

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania,Uganda, and Zambia

Objectives

To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence.

Methods

Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months.

Results

Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms.

Conclusions

Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.     

Measuring the Impact of Antiretroviral Therapy Roll-Out on Population Level Fertility in Three African Countries

Background

UNAIDS official estimates of national HIV prevalence are based on trends observed in antenatal clinic surveillance, after adjustment for the reduced fertility of HIV positive women. Uptake of ART may impact on the fertility of HIV positive women, implying a need to re-estimate the adjustment factors used in these calculations. We analyse the effect of antiretroviral therapy (ART) provision on population-level fertility in Southern and East Africa, comparing trends in HIV infected women against the secular trends observed in uninfected women.

Methods

We used fertility data from four community-based demographic and HIV surveillance sites: Kisesa (Tanzania), Masaka and Rakai (Uganda) and uMkhanyakude (South Africa). All births to women aged 15–44 years old were included in the analysis, classified by mother’s age and HIV status at time of birth, and ART availability in the community. Calendar time period of data availability relative to ART Introduction varied across the sites, from 5 years prior to ART roll-out, to 9 years after. Calendar time was classified according to ART availability, grouped into pre ART, ART introduction (available in at least one health facility serving study site) and ART available (available in all designated health facilities serving study site). We used Poisson regression to calculate age adjusted fertility rate ratios over time by HIV status, and investigated the interaction between ART period and HIV status to ascertain whether trends over time were different for HIV positive and negative women.

Results

Age-adjusted fertility rates declined significantly over time for HIV negative women in all four studies. However HIV positives either had no change in fertility (Masaka, Rakai) or experienced a significant increase over the same period (Kisesa, uMkhanyakude). HIV positive fertility was significantly lower than negative in both the pre ART period (age adjusted fertility rate ratio (FRR) range 0.51 95%CI 0.42–0.61 to 0.73 95%CI 0.64–0.83) and when ART was widely available (FRR range 0.57 95%CI 0.52–0.62 to 0.83 95%CI 0.78–0.87), but the difference has narrowed. The interaction terms describing the difference in trends between HIV positives and negatives are generally significant.

Conclusions

Differences in fertility between HIV positive and HIV negative women are narrowing over time as ART becomes more widely available in these communities. Routine adjustment of ANC data for estimating national HIV prevalence will need to allow for the impact of treatment.     

Evaluating the Impact of Test-and-Treat on the HIV Epidemic among MSM in China Using a Mathematical Model

Background

Various studies have modeled the impact of test-and-treat policies on the HIV epidemics worldwide. However, few modeling studies have taken into account China’s context. To understand the potential effect of test-and-treat on the HIV epidemic among men who have sex with men (MSM) in China, we developed a mathematical model to evaluate the impact of the strategy.

Method

Based on the natural history of the CD4 count of people living with HIV and AIDS (PLWHA), we constructed a dynamic compartmental model of HIV transmission among Chinese MSM to project the number of HIV new infections and prevalence over 10 years. We predicted the annual number of HIV new infections and the total number of MSM living with HIV and AIDS (based on Beijing data) between 2010 and 2022 under the following conditions: (1) current practice (testing rate of 50% and ART coverage of 39%); (2) both testing rate and ART coverage increasing to 70% in 2013; (3) both testing rate and ART coverage increasing to 90% in 2013; and (4) both testing rate and ART coverage increasing gradually every year until 90% since 2013.

Results

Based on our model, if the HIV test-and-treat policy was implemented among Chinese MSM, the total number of HIV new infections over 10 years (2013-2022) would be reduced by 50.6-70.9% compared with the current policy. When ART coverage for PLWHA increased to 58% since 2013, the ‘turning point’ would occur on the curve of HIV new infections by 2015. A 25% reduction in annual number of HIV new infections by 2015 might be achieved if the testing rate increased from 50% to 70% and treatment coverage for PLWHA increased to 55% since 2013.

Conclusion

Implementation of the test-and-treat strategy may significantly reduce HIV new infections among MSM in China. Great efforts need to be made to scale up HIV testing rate and ART coverage among Chinese MSM.     

Estimating the Impact of Earlier ART Initiation and Increased Testing Coverage on HIV Transmission among Men Who Have Sex with Men in Mexico using a Mathematical Model

Objective

To estimate the impact of late ART initiation on HIV transmission among men who have sex with men (MSM) in Mexico.

Methods

An HIV transmission model was built to estimate the number of infections transmitted by HIV-infected men who have sex with men (MSM-HIV+) MSM-HIV+ in the short and long term. Sexual risk behavior data were estimated from a nationwide study of MSM. CD4⁺ counts at ART initiation from a representative national cohort were used to estimate time since infection. Number of MSM-HIV+ on treatment and suppressed were estimated from surveillance and government reports. Status quo scenario (SQ), and scenarios of early ART initiation and increased HIV testing were modeled.

Results

We estimated 14239 new HIV infections per year from MSM-HIV+ in Mexico. In SQ, MSM take an average 7.4 years since infection to initiate treatment with a median CD4⁺ count of 148 cells/mm³(25^th-75^th percentiles 52–266). In SQ, 68% of MSM-HIV+ are not aware of their HIV status and transmit 78% of new infections. Increasing the CD4⁺ count at ART initiation to 350 cells/mm³ shortened the time since infection to 2.8 years. Increasing HIV testing to cover 80% of undiagnosed MSM resulted in a reduction of 70% in new infections in 20 years. Initiating ART at 500 cells/mm³ and increasing HIV testing the reduction would be of 75% in 20 years.

Conclusion

A substantial number of new HIV infections in Mexico are transmitted by undiagnosed and untreated MSM-HIV+. An aggressive increase in HIV testing coverage and initiating ART at a CD4 count of 500 cells/mm³ in this population would significantly benefit individuals and decrease the number of new HIV infections in Mexico.     

Pregnancy Prevention and Condom Use Practices among HIV-Infected Women on Antiretroviral Therapy Seeking Family Planning in Lilongwe,Malawi

Background

Programs for integration of family planning into HIV care must recognize current practices and desires among clients to appropriately target and tailor interventions. We sought to evaluate fertility intentions, unintended pregnancy, contraceptive and condom use among a cohort of HIV-infected women seeking family planning services within an antiretroviral therapy (ART) clinic.

Methods

200 women completed an interviewer-administered questionnaire during enrollment into a prospective contraceptive study at the Lighthouse Clinic, an HIV/ART clinic in Lilongwe, Malawi, between August and December 2010.

Results

Most women (95%) did not desire future pregnancy. Prior reported unintended pregnancy rates were high (69% unplanned and 61% unhappy with timing of last pregnancy). Condom use was inconsistent, even among couples with discordant HIV status, with lack of use often attributed to partner’s refusal. Higher education, older age, lower parity and having an HIV negative partner were factors associated with consistent condom usage.

Discussion

High rates of unintended pregnancy among these women underscore the need for integ rating family planning, sexually transmitted infection (STI) prevention, and HIV services. Contraceptive access and use, including condoms, must be improved with specific efforts to enlist partner support. Messages regarding the importance of condom usage in conjunction with more effective modern contraceptive methods for both infection and pregnancy prevention must continue to be reinforced over the course of ongoing ART treatment.     

Tuberculosis Case Fatality and Other Causes of Death among Multidrug-Resistant Tuberculosis Patients in a High HIV Prevalence Setting, 2000-2008, South Africa

Introduction

South Africa has the highest reported rates of multi-drug resistant TB in Africa, typified by poor treatment outcomes, attributable mainly to high default and death rates. Concomitant HIV has become the strongest predictor of death among MDR-TB patients, while anti-retroviral therapy (ART) has dramatically reduced mortality. TB Case fatality rate (CFR) is an indicator that specifically reports on deaths due to TB.

Aim

The aim of this paper was to investigate causes of death amongst MDR-TB patients, the contribution of conditions other than TB to deaths, and to determine if causes differ between HIV-uninfected patients, HIV-infected patients receiving ART and those without ART.

Methods

We carried out a retrospective review of data captured from the register of the MDR-TB programme of the North West Province, South Africa. We included 671 patients treated between 2000–2008; 59% of the cohort was HIV-infected and 33% had received ART during MDR treatment. The register contained data on treatment outcomes and causes of death.

Results

Treatment outcomes between HIV-uninfected cases, HIV-infected cases receiving ART and HIV-infected without ART differed significantly (p<0.000). The cohort death rate was 24%, 13% for HIV-uninfected cases and 31% for HIV-infected cases. TB caused most of the deaths, resulting in a cohort CFR of 15%, 9% for HIV-uninfected cases and 20% for HIV-infected cases. Cohort mortality rate due to other conditions was 2%. AIDS-conditions rather than TB caused significantly more deaths among HIV-infected cases receiving ART than those not (p = 0.02).

Conclusions

The deaths among HIV-infected individuals contribute substantially to the high death rate. ART co-therapy protected HIV-infected cases from death due to TB and AIDS-conditions. Mechanisms need to be in place to ensure that HIV-infected individuals are retained in care upon completion of their MDR-TB treatment.     

Progress in Reversing the HIV Epidemic through Intensified Access to Antiretroviral Therapy: Results from a Nationally Representative Population-Based Survey in Kenya, 2012

Background

In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) called for 90% of persons living with HIV (PLHIV) to know their status, 90% of these to be on antiretroviral therapy (ART), and 90% of these to be virally suppressed by 2020 (90-90-90). It is not clear whether planned ART scale-up in countries whose eligibility criteria for ART initiation are based on recommendations from the 2013 World Health Organization treatment guidelines will be sufficient to meet UNAIDS'' new global targets.

Materials and Methods

Using data from a nationally representative population-based household survey of persons in Kenya we compared coverage and unmet need associated with HIV diagnosis, ART, and viral suppression among PLHIV aged 15–64 years in 2012 based on criteria outlined in the 2014 national ART guidelines and UNAIDS’ 90-90-90 goals. Estimates were weighted to account for sampling probability and nonresponse.

Results

Eight in ten PLHIV aged 15–64 years needed ART based on treatment eligibility. Need for treatment based on the national treatment policy was 97.4% of treatment need based on UNAIDS’ 90-90-90 goals, requiring an excess of 24,000 PLHIV to access treatment beyond those eligible for ART to achieve UNAIDS’ 90-90-90 treatment target. The gap in treatment coverage was high, ranging from 43.1% nationally to 52.3% in Nyanza among treatment-eligible PLHIV and 44.6% nationally to 52.4% in Nyanza among all PLHIV.

Conclusion

Maintaining the current pace of ART scale-up in Kenya will result in thousands of PLHIV unreached, many with high viral load and at-risk of transmitting infection to others. Careful strategies for reaching 90-90-90 will be instrumental in determining whether intensified access to treatment can be achieved to reach all who require ART.     

Use of Surveillance Data on HIV Diagnoses with HIV-Related Symptoms to Estimate the Number of People Living with Undiagnosed HIV in Need of Antiretroviral Therapy

Background

It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART).

Methods

The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method.

Results

For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150–199 cells/mm³, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150–199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29–100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum.

Conclusions

The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.     

Trends in CD4 Count Testing,Retention in Pre-ART Care,and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti

Background

High attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is widely reported. Though treatment guidelines have changed to broaden ART eligibility and services have been widely expanded over the past decade, data on the temporal trends in pre-ART outcomes are limited; such data would be useful to guide future policy decisions.

Methods

We evaluated temporal trends and predictors of retention for each step from HIV testing to ART initiation over the past decade at the GHESKIO clinic in Port-au-Prince Haiti. The 24,925 patients >17 years of age who received a positive HIV test at GHESKIO from March 1, 2003 to February 28, 2013 were included. Patients were followed until they remained in pre-ART care for one year or initiated ART.

Results

24,925 patients (61% female, median age 35 years) were included, and 15,008 (60%) had blood drawn for CD4 count within 12 months of HIV testing; the trend increased over time from 36% in Year 1 to 78% in Year 10 (p<0.0001). Excluding transfers, the proportion of patients who were retained in pre-ART care or initiated ART within the first year after HIV testing was 84%, 82%, 64%, and 64%, for CD4 count strata ≤200, 201 to 350, 351 to 500, and >500 cells/mm³, respectively. The trend increased over time for each CD4 strata, and in Year 10, 94%, 95%, 79%, and 74% were retained in pre-ART care or initiated ART for each CD4 strata. Predictors of pre-ART attrition included male gender, low income, and low educational status. Older age and tuberculosis (TB) at HIV testing were associated with retention in care.

Conclusions

The proportion of patients completing assessments for ART eligibility, remaining in pre-ART care, and initiating ART have increased over the last decade across all CD4 count strata, particularly among patients with CD4 count ≤350 cells/mm³. However, additional retention efforts are needed for patients with higher CD4 counts.     

Factors Associated with Variations in Population HIV Prevalence across West Africa: Findings from an Ecological Analysis

Background

Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this.

Methods

National, urban and rural data on HIV prevalence, the percentage of younger (15–24) and older (25–49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other.

Findings

National population HIV prevalence varies between 0 4–2 9% for men and 0 4–5.6% for women. ART coverage ranges from 6–23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence.

Interpretation

In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners.     

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

Background

We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

Methods

Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

Results

A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

Conclusion

In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.     

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha,South Africa: Impact on Mortality and Treatment Success

Setting

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.

Objective

To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.

Design

A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.

Results

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm³. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).

Conclusions

Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.     

Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

Background

Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART.

Methods and Findings

We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting.

Conclusions

Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care.     

Factors Associated with Retention to Care in an HIV Clinic in Gabon,Central Africa

Background

Retention to HIV care is vital for patients’ survival, to prevent onward transmission and emergence of drug resistance. Travelling to receive care might influence adherence. Data on the functioning of and retention to HIV care in the Central African region are limited.

Methods

This retrospective study reports outcomes and factors associated with retention to HIV care at a primary HIV clinic in Lambaréné, Gabon. Adult patients who presented to this clinic between January 2010 and January 2012 were included. Outcomes were retention in care (defined as documented show-up for clinical visits, regardless of delay) or LTFU (defined as a patient not retained in care; on ART or ART naïve, not returning to care during the study period with a patient delay for scheduled visits of more than 6 months), and mortality. Cox regression analysis was used to assess factors associated with respective outcomes. Qualitative data on reasons for LTFU were obtained from focus-group discussions.

Results

Of 223 patients included, 67.3% were female. The mean age was 40.5 (standard deviation 11.4) years and the median CD4 count 275 (interquartile range 100.5–449.5) cells/μL. In total, 34.1% were lost to follow up and 8.1% died. Documented tuberculosis was associated with increased risk of being LTFU (adjusted hazard ratio (aHR) 1.80, 95% confidence interval (95% CI) 1.05–3.11, P = 0.03), whereas early starting anti-retroviral therapy (ART) was associated with a decreased risk of LTFU (aHR 0.43, 95%CI 0.24–0.76, P = 0.004), as was confirmed by qualitative data.

Conclusions

Retention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care.     

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective

We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.

Design

Cohort study of adult patients on ART.

Setting

GHESKIO Clinic in Port-au-Prince, Haiti.

Participants

4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.

Main Outcome Measure

Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.

Results

In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.

Conclusions

If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.