The association of HIV with chronic morbidity and inflammatory markers (cytokines) in older adults (50+years) is potentially relevant for clinical care, but data from African populations is scarce.
To examine levels of chronic morbidity by HIV and ART status in older adults (50+years) and subsequent associations with selected pro-inflammatory cytokines and body mass index.
Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina), arthritis, stroke, hypertension, asthma and diabetes) and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha) by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance.
Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92) of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR) of having elevated inflammation markers of IL6 (>1.56pg/mL) was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21) and not on (aPOR 1.94; 95%CI: 1.11-3.41) ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004) of having non-clinically significant raised hsCRP levels(>1ug/mL); ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9ug/mL;p=0.008).
Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease screening would ensure health care reaches all older adults in need.
To determine rates of, and factors associated with, disengagement from care in a decentralised antiretroviral programme.
Adults (≥16 years) who initiated antiretroviral therapy (ART) in the Hlabisa HIV Treatment and Care Programme August 2004–March 2011 were included. Disengagement from care was defined as no clinic visit for 180 days, after adjustment for mortality. Cumulative incidence functions for disengagement from care, stratified by year of ART initiation, were obtained; competing-risks regression was used to explore factors associated with disengagement from care.
A total of 4,674 individuals (median age 34 years, 29% male) contributed 13 610 person-years of follow-up. After adjustment for mortality, incidence of disengagement from care was 3.4 per 100 person-years (95% confidence interval (CI) 3.1–3.8). Estimated retention at 5 years was 61%. The risk of disengagement from care increased with each calendar year of ART initiation (P for trend <0.001). There was a strong association between disengagement from care and higher baseline CD4+ cell count (subhazard ratio (SHR) 1.94 (P < 0.001) and 2.35 (P < 0.001) for CD4+ cell count 150–200 cells/μl and >200 cells/μl respectively, compared with CD4 count <50 cells/μl). Of those disengaged from care with known outcomes, the majority (206/303, 68.0%) remained resident within the local community.
Increasing disengagement from care threatens to limit the population impact of expanded antiretroviral coverage. The influence of both individual and programmatic factors suggests that alternative service delivery strategies will be required to achieve high rates of long-term retention.
HIV-1; antiretroviral agents; primary health care; delivery of health care; lost to follow-up; disengagement from care
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.
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.
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.
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.
AIDS; antiretroviral therapy; HIV; sexual risk behaviours; ART-eligible; pre-ART
Using sexual behaviour survey data, we examine the methodological choice for the time period underlying the UNAIDS Reference Group recommended ‘point prevalence’ indicator for concurrency. Results confirm that 6 months before the interview is a good time point for calculating the recommended indicator, and that this retrospective estimate is substantially lower than the estimate of concurrency based on the number of current partnerships. The discrepancy is only partially explained by disproportionate missing data in those with more sexual partners.
Antiretroviral therapy (ART) roll-out is fraught with challenges, many with serious repercussions. We explored and described patient behaviour-related challenges from the perspective of health care providers from non-governmental organisations involved in ART programmes in KwaZulu-Natal, South Africa.
A descriptive case study design using qualitative approach was applied during this study. Data was collected from nine key informants from the three biggest NGOs involved in ART roll-out using in-depth semi-structured interviews. Transcribing and coding for emergent themes was done by two independent reviewers. Ethical approval for the study was granted by the UNISA research ethics committee of The Faculty of Health Sciences. Written consent was obtained from directors of the three NGOs involved and individual audio taped informed consent was obtained from all study participants prior to data collection.
Findings revealed six broad areas of patient behaviour challenges. These were patient behaviour related to socio-economic situation of patient (skipping of medication due to lack of food, or due to lack of transport fees), belief systems (traditional and religious), stigma (non- disclosure), sexual practices (non-acceptability of condoms, teenage pregnancies), escapism (drug and alcohol abuse) and opportunism (skipping medication in order to access disability grant, teenage pregnancies in order to access child grant).
New programmes need to address patient behaviour as a complex phenomenon requiring a multi-pronged approach that also addresses social norms and institutions. In the face of continued ART scale up, this is further evidence for the need for multi-sectoral collaboration to ensure successful and sustainable ART roll-out.
Patient behaviour; ART roll-out; Health care provider perspective; Non-governmental organisation; KwaZulu-Natal
Tuberculosis control in sub-Saharan Africa has long been hampered by poor diagnostics and weak health systems. New molecular diagnostics, such as the Xpert® MTB/RIF assay, have the potential to improve patient outcomes. We present a cluster randomised trial designed to evaluate whether the positioning of this diagnostic system within the health system has an impact on important patient-level outcomes.
This pragmatic cluster randomised clinical trial compared two positioning strategies for the Xpert MTB/RIF system: centralised laboratory versus primary health care clinic. The cluster (unit of randomisation) is a 2-week time block at the trial clinic. Adult pulmonary tuberculosis suspects with confirmed human immunodeficiency virus infection and/or at high risk of multidrug-resistant tuberculosis are enrolled from the primary health care clinic. The primary outcome measure is the proportion of culture-confirmed pulmonary tuberculosis cases initiated on appropriate treatment within 30 days of initial clinic visit. Univariate logistic regression will be performed as the primary analysis using generalised estimating equations with a binomial distribution function and a logit link.
Diagnostic research tends to focus only on performance of diagnostic tests rather than on patient-important outcomes. This trial has been designed to improve the quality of evidence around diagnostic strategies and to inform the scale-up of new tuberculosis diagnostics within public health systems in high-burden settings.
Current Controlled Trials ISRCTN18642314; South African National Clinical Trials Registry DOH-27-0711-3568.
Tuberculosis; Multidrug-resistant tuberculosis; HIV; Molecular diagnostics; Point-of-care systems; Clinical trial
Risk of antenatal depression has been shown to be elevated in Southern Africa and can impact maternal and child outcomes, especially in the context of the Human Immunodeficiency Virus (HIV). Brief screening methods may optimize access to care during pregnancy, particularly where resources are scarce. This research evaluated shorter versions of the Edinburgh Postnatal Depression Scale (EPDS) to detect antenatal depression. This cross-sectional study at a large primary health care (PHC) facility recruited a consecutive series of 109 antenatal attendees in rural South Africa. Women were in the second half of pregnancy and completed the EPDS and Structured Clinical Interview for Depression (SCID). The recommended EPDS cutoff (≥13) was used to determine probable depression. Four versions, including the 10-item scale, seven-item depression, and novel three- and five-item versions developed through regression analysis, were evaluated using receiver operating characteristic (ROC) analysis. High numbers of women 51/109 (47 %) were depressed, most depression was chronic, and nearly half of the women were HIV positive 49/109 (45 %). The novel three-item version had improved positive predictive value (PPV) over the 10-item version and equivalent specificity to the seven-item depression subscale; the novel five-item provided the best overall performance in terms of ROC and Cronbach's reliability statistics and had improved specificity. The brevity, sensitivity, and reliability of the short and ultrashort versions could facilitate widespread community screening. The usefulness of the novel three- and five-item versions are underscored by the fact that sensitivity is important at first screening, while specificity becomes more important at higher levels of care. Replication in larger samples is required.
Antenatal depression; Screening; EPDS; Short; Ultrashort; HIV
To describe and compare the health status, emotional wellbeing, and functional status of older people in Uganda and South Africa who are HIV infected or affected by HIV in their families.
Data came from the general population cohort and Entebbe cohort of the Medical Research Council/Uganda Virus Research Institute, and from the Africa Centre Demographic Information System through cross-sectional surveys in 2009/10 using instruments adapted from the World Health Organization (WHO) Study on Global Ageing and adult health (SAGE). Analysis was based on 932 people aged 50 years or older (510 Uganda, 422 South Africa).
Participants in South Africa were slightly younger (median age − 60 years in South Africa, 63 in Uganda), and more were currently married, had no formal education, were not working, and were residing in a rural area. Adjusting for socio-demographic factors, older people in South Africa were significantly less likely to have good functional ability [adjusted odds ratio (aOR) 0.72, 95% CI 0.53–0.98] than those in Uganda, but were more likely to be in good subjective wellbeing (aOR 2.15, 95% CI 1.60–2.90). South Africans were more likely to be obese (aOR 5.26, 95% CI 3.46–8.00) or to be diagnosed with hypertension (aOR 2.77, 95% CI 2.06–3.73).
Discussion and conclusions
While older people’s health problems are similar in the two countries, marked socio-demographic differences influence the extent to which older people are affected by poorer health. It is therefore imperative when designing policies to improve the health and wellbeing of older people in sub-Saharan Africa that the region is not treated as a homogenous entity.
South Africa; Uganda; older people; health status; functional ability; subjective wellbeing
To describe predictors of pregnancy and changes in pregnancy incidence among HIV-positive women accessing HIV clinical care.
Data were obtained through the linkage of two separate studies; the UK Collaborative HIV Cohort study (UK CHIC), a cohort of adults attending 13 large HIV clinics, and the National Study of HIV in Pregnancy and Childhood (NSHPC), a national surveillance study of HIV-positive pregnant women. Pregnancy incidence was measured using the proportion of women in UK CHIC with a pregnancy reported to NSHPC. Generalised estimating equations were used to identify predictors of pregnancy and assess changes in pregnancy incidence in 2000-2009.
The number of women accessing care at UK CHIC sites increased as did the number of pregnancies (from 72 to 230). Older women were less likely to have a pregnancy (adjusted Relative Rate (aRR) 0.44 per 10 year increment in age [95% CI [0.41-0.46], p<0.001) as were women with CD4<200 cells/mm3 compared with CD4 200-350 cells/mm3 (aRR 0.65 [0.55-0.77] p<0.001) and women of white ethnicity compared with women of black-African ethnicity (aRR 0.67 [0.57-0.80], p<0.001). The likelihood that women had a pregnancy increased over the study period (aRR 1.05 [1.03-1.07], p<0.001). The rate of change did not significantly differ according to age group, ART use, CD4 group or ethnicity.
The pregnancy rate among women accessing HIV clinical care increased in 2000-2009. HIV-positive women with, or planning, a pregnancy require a high level of care and this is likely to continue and increase as more women of older age have pregnancies.
HIV; pregnancy; pregnancy rate; maternal age; highly active antiretroviral therapy; maternal-fetal infection transmission; United Kingdom
In the context of low rates of participation in a prospective, population-based HIV surveillance programme, researchers at a surveillance site in rural KwaZulu-Natal, South Africa, conducted an operational study from January 2009 to February 2010, with the aim of improving participation rates, particularly in the provision of dried blood spots for the surveillance. Findings suggest, firstly, that consent to participation in the HIV surveillance is informed by the dynamics of relationality in the HIV surveillance “consent encounter.”
Secondly, it emerged that both fieldworkers and participants found it difficult to differentiate between HIV surveillance and HIV testing in the surveillance procedure, and tended to understand and explain giving blood under the aegis of the surveillance as an HIV test. The conflation of surveillance and testing, we argue, is not merely a semantic confusion, but reveals an important tension inherent to global health research between individual risks and benefits and collective good, or between private morality and public good. Because of these structural tensions, we suggest, the HIV surveillance consent encounter activates multiple gift economies in the collection of blood samples. Thinking beyond the complex ethical dimensions provoked by new forms of long-term surveillance and health research, we therefore suggest that deepening relations between scientists, fieldworkers, and study participants in locality deserve more careful methodological consideration and descriptive attention.
► Consent and refusal to HIV surveillance take place in the context of everyday social relations and local exchange economies. ► Local notions of gift and relatedness and rights and obligations frame exchanges of blood for knowledge in HIV surveillance. ► Participants struggled to differentiate HIV surveillance from testing, thereby blurring concepts of risk and benefit. ► Surveillance programs should engage with local constructions of risk, benefit and relatedness in research design.
South Africa; Ethics; Surveillance research; Obligation and reciprocity; Kinship; Local relations; HIV testing; Participation
Research into HIV and men who have sex with men’s (MSM) health in South Africa has been largely confined to the metropolitan centres. Only two studies were located making reference to MSM in rural contexts or same-sex behaviors among men in the same. There is growing recognition in South Africa that MSM are not only disproportionately affected by HIV and have been underserved by the country’s national response, but that they contribute significantly to sustaining the high number of new infections recorded each year. We argue that to meet the objectives of the country’s national strategic plan for HIV, STI and TB it is important we know how these behaviours may be contributing to the sustained rural HIV epidemic in the youngest age groups and determine what constitutes appropriate and feasible programmatic response that can be implemented in the country’s public sector health services.
Rural; MSM; HIV prevention; Research; South Africa
Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.
We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.
For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$ 141 million. For universal treatment (‘treatment as prevention’), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).
Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.
Human resources for health; HIV; South Africa; Antiretroviral treatment
Hypertension and excess body weight are major risk factors of cardiovascular morbidity and mortality in developing countries. In countries with a high HIV prevalence, it is unknown how increased antiretroviral treatment and care (ART) coverage has affected the prevalence of overweight, obesity, and hypertension. We conducted a health survey in 2010 based on the WHO STEPwise approach in 14,198 adult resident participants of a demographic surveillance area in rural South Africa to investigate factors associated with hypertension and excess weight including HIV infection and ART status. Women had a significantly higher median body mass index (BMI) than men (26.4 vs. 21.2 kg/m2, p<0.001). The prevalence of obesity (BMI≥30 kg/m2) in women (31.3%, 95% confidence interval (CI) 30.2–32.4) was 6.5 times higher than in men (4.9%, 95% CI 4.1–5.7), whereas prevalence of hypertension (systolic or diastolic blood pressure≥140 or 90 mm Hg, respectively) was 1.4 times higher in women than in men (28.5% vs 20.8%, p<0.001). In multivariable regression analysis, both hypertension and obesity were significantly associated with sex, age, HIV and ART status. The BMI of women and men on ART was on average 3.8 (95% CI 3.2–3.8) and 1.7 (95% CI 0.9–2.5) kg/m2 lower than of HIV-negative women and men, respectively. The BMI of HIV-infected women and men not on ART was on average 1.2 (95% CI 0.8–1.6) and 0.4 (95% CI -0.1–0.9) kg/m2 lower than of HIV-negative women and men, respectively. Obesity was a bigger risk factor for hypertension in men (adjusted odds ratio (aOR) 2.99, 95% CI 2.00–4.48) than in women (aOR 1.64, 95% CI 1.39–1.92) and overweight (25≤BMI<30) was a significant risk factor for men only (aOR 1.53 95% CI 1.14–2.06). Our study suggests that, cardiovascular risk factors of hypertension and obesity differ substantially between women and men in rural South Africa.
The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV-positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning.
A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counselling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence.
The proportion of MTCT from mothers who seroconverted after their first antenatal visit was 26% (95% CI: 22-30%) in 2008, or 15 000 out of 57 000 infections. It is estimated that by 2014, total MTCT will reduce to 39 000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13 000 per annum, accounting for 34% (95% CI: 29-39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010-15 period would reduce by 28% (95% CI: 25-31%), from 39 000 to 28 000 per annum.
Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the paediatric HIV burden, and needs greater attention in the planning of PMTCT programmes.
HIV/AIDS; vertical transmission; mathematical model; South Africa
Despite the introduction of blood donor screening, worldwide, children continue to become infected with HCV via un-sterile medical injections, receipt of unscreened blood and isolated hospital contamination outbreaks. It is plausible that the natural history and disease progression in these children might differ from that of their vertically infected counterparts.
Materials and Methods
Vertically and parenterally HCV infected children were prospectively followed within the European Paediatric HCV Network and the UK National HCV Register respectively. Biological profiles were compared.
Vertically and parenterally HCV infected children differed in terms of some key characteristics including the male:female ratio and the proportion of children receiving therapy. Parenterally infected children were more likely to have at least one hepatomegaly event during follow-up, 20% vs. 10%. Parenteral infection did not significantly affect the odds of being consistently viraemic, AOR 1.14 p=0.703 and there was no significant difference in the odds of having consistently elevated ALT levels and mode of acquisition, AOR 0.83 p=0.748. The proportion of children with 2 or more markers of HCV infection did not differ significantly by mode of acquisition, χ21.13 p=0.288.
This analysis does not support substantial differences between vertically and parenterally infected groups but there are specific mechanisms identified requiring further investigation. Given the continued parenteral infection of children worldwide it is vital that knowledge of disease progression in this group is accurate and that the differences in comparison to vertically infected children are clarified to inform more accurate and individualised clinical management.
biological markers; children; hepatitis C virus; mode of acquisition
This article presents a detailed description of a community mobilization intervention involving women’s groups in Mchinji District, Malawi. The intervention was implemented between 2005 and 2010.
The intervention aims to build the capacities of communities to take control of the mother and child health issues that affect them. To achieve this it comprises trained local female facilitators establishing groups and using a manual, participatory rural appraisal tools and picture cards to guide them through a community action cycle to identify and implement solutions to mother and child health problems. Significant resource inputs include salaries for facilitators and supervisors, and training, equipment and materials to support their work with groups.
It is hypothesized that the groups will catalyse community collective action to address mother and child health issues and improve the health and reduce the mortality of mothers and children. Their impact, implementation and cost-effectiveness have been rigorously evaluated through a randomized controlled trial design. The results of these evaluations will be reported in 2011.
Maternal and child survival are highly correlated, but the contribution of HIV infection on this relationship, and in particular the impact of HIV treatment has not been quantified. We estimate the association between maternal HIV and treatment and under-5 child mortality in a rural population in South Africa.
All children born between January 2000-January 2007 in the Africa Centre Demographic Surveillance Area were included. Maternal HIV status information was available from HIV surveillance; maternal antiretroviral treatment (ART) from the HIV Treatment Programme database and linked to surveillance data. Mortality rates were computed as deaths per 1000 person-years observed. Time-varying maternal HIV effect (positive, negative, ART) on U5MR was assessed in Cox regression, adjusting for other factors associated with under-5 mortality.
9,068 mothers delivered 12,052 children, of whom 947 (7.9%) died before age 5. Infant mortality rate (IMR) declined by 49% from 69.0 in 2000 to 35.5 in 2006 deaths per 1000 person-years observed; a significantly decline was observed post-ART (2004-2006). The estimated proportion of deaths across all age groups were higher among the children born to the HIV-positive and HIV-not reported status women than among children of HIV-negative women. Multivariably, mortality in children of mothers on ART was not significantly different from children of HIV-negative mothers (aHR 1.29, 0.53-3.17; p=0.572).
These findings highlight the importance of maternal HIV treatment with direct benefits of improved survival among all children under-5. Timely HIV treatment for eligible women is required to benefit both mothers and children.
To describe antiretroviral therapy (ART) use and clinical status, at start of and during pregnancy, for HIV-positive women receiving ART at conception, including the proportion conceiving on drugs (efavirenz and didanosine) not recommended for use in early pregnancy.
Women with a pregnancy resulting in a live birth after 1995 (n=1,537) were identified in an observational cohort of patients receiving HIV care at 12 clinics in the UK by matching records with national pregnancy study data. Treatment and clinical data were analysed for 375 women conceiving on ART, including logistic regression to identify factors associated with changing regimen during pregnancy.
Of the 375 women on ART at conception, 39 (10%) conceived on dual therapy, 306 (82%) on triple therapy and 30 (8%) on >3 drugs. In total, 116 (31%) women conceived on a regimen containing efavirenz or didanosine (69 efavirenz, 54 didanosine, 7 both). Overall, 38% (143) switched regimen during pregnancy, of whom 41% (n=48) had a detectable viral load (≥50 copies/ml) around that time. Detectable viral load was associated with increased risk of regimen change (adjusted odds ratio 2.2, 95% confidence interval [1.3, 3.8]), while women on efavirenz at conception were three times more likely to switch than women on other drugs (3.3, [1.8, 6.0]). Regimen switching was also associated with calendar year at conception (0.9, [0.8-1.0]).
These findings reinforce the need for careful consideration of ART use among women planning or likely to have a pregnancy in order to reduce viral load before pregnancy and avoid drugs not recommended for early antenatal use.
HIV; pregnancy; antiretroviral agents; antiretroviral therapy; United Kingdom
The only successful HIV vaccine trial to date is the RV144 trial of the ALVAC/AIDSVAX vaccine in Thailand, which showed an overall incidence reduction of 31%. Most cases were prevented in the first year, suggesting a rapidly waning efficacy. Here, we predict the population level impact and cost-effectiveness of practical implementation of such a vaccine in a setting of a generalised epidemic with high HIV prevalence and incidence.
We used STDSIM, an established individual-based microsimulation model, tailored to a rural South African area with a well-functioning HIV treatment and care programme. We estimated the impact of a single round of mass vaccination for everybody aged 15–49, as well as 5-year and 2-year revaccination strategies for young adults (aged 15–29). We calculated proportion of new infections prevented, cost-effectiveness indicators, and budget impact estimates of combined ART and vaccination programmes.
A single round of mass vaccination with a RV144-like vaccine will have a limited impact, preventing only 9% or 5% of new infections after 10 years at 60% and 30% coverage levels, respectively. Revaccination strategies are highly cost-effective if vaccine prices can be kept below 150 US$/vaccine for 2-year revaccination strategies, and below 200 US$/vaccine for 5-year revaccination strategies. Net cost-savings through reduced need for HIV treatment and care occur when vaccine prices are kept below 75 US$/vaccine. These results are sensitive to alternative assumptions on the underlying sexual network, background prevention interventions, and individual’s propensity and consistency to participate in the vaccination campaign.
A modestly effective vaccine can be a cost-effective intervention in highly endemic settings. To predict the impact of vaccination strategies in other endemic situations, sufficient knowledge of the underlying sexual network, prevention and treatment interventions, and individual propensity and consistency to participate, is key. These issues are all best addressed in an individual-based microsimulation model.
HIV vaccine; Mathematical model; Microsimulation model; South Africa; Cost-effectiveness
The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone.
Women in UK CHIC receiving HIV-clinical care in 1996–2009, were found in the NSHPC dataset by initially ‘linking’ records with identical date-of-birth, linked records were then accepted as a genuine ‘match’, if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively).
Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.
Data linkage; HIV; Pregnant women; Antiretroviral therapy; Cohort analysis; United Kingdom
Breast-feeding substantially increases the risk of HIV-1 transmission from mother to child, and although peripartum antiretroviral therapy prophylaxis significantly decreases the risk of mother-to-child transmission around the time of delivery, this approach does not affect breast-feeding transmission. Increased maternal RNA viral load in plasma and breast milk is strongly associated with increased risk of transmission through breast-feeding, as is breast health, and it has been suggested that exclusive breast-feeding could be associated with lower rates of breast-feeding transmission than mixed feeding of both breast- and other milk or feeds. Transmission through breast-feeding can take place at any point during lactation, and the cumulative probability of acquisition of infection increases with duration of breast-feeding. HIV-1 has been detected in breast milk in cell-free and cellular compartments; infant gut mucosal surfaces are the most likely site at which transmission occurs. Innate and acquired immune factors may act most effectively in combination to prevent primary HIV-1 infection by breast milk.
breastfeeding; mother-to-child transmission; postnatal transmission; risk factors; mechanisms
HIV-1 transmitted drug resistance (TDR) could reverse the gains of antiretroviral rollout. To ensure that current first-line therapies remain effective, TDR levels in recently infected treatment-naive patients need to be monitored. A literature review and data mining exercise was carried out to determine the temporal trends in TDR in South Africa. In addition, 72 sequences from seroconvertors identified from Africa Centre's 2010 HIV surveillance round were also examined for TDR. Publicly available data on TDR were retrieved from GenBank, curated in RegaDB, and analyzed using the Calibrated Population Resistance Program. There was no evidence of TDR from the 2010 rural KwaZulu Natal samples. Ten datasets with a total of 1618 sequences collected between 2000 and 2010 were pooled to provide a temporal analysis of TDR. The year with the highest TDR rate was 2002 [6.67%, 95% confidence interval (CI): 3.09–13.79%; n=6/90]. After 2002, TDR levels returned to <5% (WHO low-level threshold) and showed no statistically significant increase in the interval between 2002 and 2010. The most common mutations were associated with NNRTI resistance, K103N, followed by Y181C and Y188C/L. Five sequences had multiple resistance mutations associated with NNRTI resistance. There is no evidence of TDR in rural KwaZulu-Natal. TDR levels in South Africa have remained low following a downward trend since 2003. Continuous vigilance in monitoring of TDR is needed as more patients are initiated and maintained onto antiretroviral therapy.
Background Previously, HIV epidemic models have used a double Weibull curve to represent high initial and late mortality of HIV-infected children, without distinguishing timing of infection (peri- or post-natally). With more data on timing of infection, which may be associated with disease progression, a separate representation of children infected early and late was proposed.
Methods Paediatric survival post-HIV infection without anti-retroviral treatment was calculated using pooled data from 12 studies with known timing of HIV infection. Children were grouped into perinatally or post-natally infected. Net mortality was calculated using cause-deleted life tables to give survival as if HIV was the only competing cause of death. To extend the curve beyond the available data, children surviving beyond 2.5 years post infection were assumed to have the same survival as young adults. Double Weibull curves were fitted to both extended survival curves to represent survival of children infected perinatally or through breastfeeding.
Results Those children infected perinatally had a much higher risk of dying than those infected through breastfeeding, even allowing for background mortality. The final-fitted double Weibull curves gave 75% survival at 5 months after infection for perinatally infected, and 1.1 years for post-natally infected children. An estimated 25% of the early infected children would still be alive at 10.6 years compared with 16.9 years for those infected through breastfeeding.
Conclusions The increase in available data has enabled separation of child mortality patterns by timing of infection allowing improvement and more flexibility in modelling of paediatric HIV infection and survival.
HIV; survival; paediatric
Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa.
Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001–2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors.
Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06–1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91–1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18–3.81 and 2.77, 95% CI: 1.56–4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79–1.79 for 34–36 weeks and 1.31, 95% CI: 0.58–2.94 for <34 weeks).
Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.
HIV; SGA; preterm; Africa; low birthweight