Early adolescent pregnancy increases risk of incident HIV infection in the Eastern Cape,South Africa: a longitudinal study

Introduction

Adolescents having unprotected heterosexual intercourse are at risk of HIV infection and unwanted pregnancy. However, there is little evidence to indicate whether pregnancy in early adolescence increases the risk of subsequent HIV infection. In this paper, we tested the hypothesis that adolescent pregnancy (aged 15 or younger) increases the risk of incident HIV infection in young South African women.

Methods

We assessed 1099 HIV-negative women, aged 15–26 years, who were volunteer participants in a cluster-randomized, controlled HIV prevention trial in the predominantly rural Eastern Cape province of South Africa. All of these young women had at least one additional HIV test over two years of follow-up. Outcomes were HIV incidence rates per 100 person years and HIV incidence rate ratios (IRRs) estimated by Poisson multivariate models. Three pregnancy categories were created for the Poisson model: early adolescent pregnancy (a first pregnancy at age 15 years or younger); later adolescent pregnancy (a first pregnancy at age 16 to 19 years); and women who did not report an adolescent pregnancy. Models were adjusted for study design, age, education, time since first sexual experience, socio-economic status, childhood trauma and herpes simplex virus type 2 infection.

Results

HIV incidence rates were 6.0 per 100 person years over two years of follow-up. The adjusted IRR was 3.02 (95% CI 1.50–6.09) for a pregnancy occurring at age 15 or younger. Women with pregnancies occurring between 16 and 19 years of age did not have a higher incidence of HIV (IRR 1.08; 95% CI 0.64–1.84). Early adolescent pregnancies were associated with higher partner numbers and a greater age difference with partners.

Conclusions

Early adolescent pregnancies increase the incidence of HIV among South African women. The higher risk is associated with sexual risk behaviours such as higher partner numbers and a greater age difference with partners rather than a biological explanation of hormonal changes during pregnancy.     

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.     

HIV incidence among people who inject drugs in the Middle East and North Africa: mathematical modelling analysis

Introduction

Emerging HIV epidemics have been documented among people who inject drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the HIV incidence among PWID due to sharing needles/syringes in MENA. It also delineates injecting drug use role as a driver of the epidemic in the population, and estimates impact of interventions.

Methods

A mathematical model of HIV transmission among PWID was applied in seven MENA countries with sufficient and recent epidemiological data and HIV prevalence ≥1% among PWID. Estimations of incident and/or prevalent infections among PWID, ex‐PWID and sexual partners of infected current and ex‐PWID were conducted.

Results

The estimated HIV incidence rate for 2017 among PWID ranged between 0.7% per person‐year (ppy) in Tunisia and 7.8% ppy in Pakistan, with Libya being an outlier (24.8% ppy). The estimated number of annual new infections was lowest in Tunisia (n = 79) and Morocco (n = 99), and highest in Iran and Pakistan (approximately n = 6700 each). In addition, 20 to 2208 and 5 to 837 new annual infections were estimated across the different countries among sexual partners of PWID and ex‐PWID respectively. Since epidemic emergence, the number of total ever acquired incident infections across countries was 706 to 90,015 among PWID, 99 to 18,244 among sexual partners of PWID, and 16 to 4360 among sexual partners of ex‐PWID. The estimated number of prevalent infections across countries was 341 to 23,279 among PWID, 119 to 16,540 among ex‐PWID, 67 to 10,752 among sexual partners of PWID, and 12 to 2863 among sexual partners of ex‐PWID. Increasing antiretroviral therapy (ART) coverage to the global target of 81% – factoring in ART adherence and current coverage – would avert about half of new infections among PWID and their sexual partners. Combining ART with harm reduction could avert over 90% and 70% of new infections among PWID and their sexual partners respectively.

Conclusions

There is considerable HIV incidence among PWID in MENA. Of all new infections ultimately due to injecting drug use, about 75% are among PWID and the rest among sexual partners. Of all prevalent infections ultimately attributed to injecting drug use as epidemic driver, about half are among PWID, 30% among ex‐PWID and 20% among sexual partners of PWID and ex‐PWID. These findings call for scale‐up of services for PWID, including harm reduction as well as testing and treatment services.

     

Trajectories of re-engagement: factors and mechanisms enabling patient return to HIV care in Zambia

Introduction

While disengagement from HIV care threatens the health of persons living with HIV (PLWH) and incidence-reduction targets, re-engagement is a critical step towards positive outcomes. Studies that establish a deeper understanding of successful return to clinical care among previously disengaged PLWH and the factors supporting re-engagement are essential to facilitate long-term care continuity.

Methods

We conducted narrative, patient-centred, in-depth interviews between January and June 2019 with 20 PLWH in Lusaka, Zambia, who had disengaged and then re-engaged in HIV care, identified through electronic medical records (EMRs). We applied narrative analysis techniques, and deductive and inductive thematic analysis to identify engagement patterns and enablers of return.

Results

We inductively identified five trajectories of care engagement, suggesting patterns in patient characteristics, experienced barriers and return facilitators that may aid intervention targeting including: (1) intermittent engagement;(2) mostly engaged; (3) delayed linkage after testing; (4) needs time to initiate antiretroviral therapy (ART); and (5) re-engagement with ART initiation. Patient-identified periods of disengagement from care did not always align with care gaps indicated in the EMR. Key, interactive re-engagement facilitators experienced by participants, with varied importance across trajectories, included a desire for physical wellness and social support manifested through verbal encouragement, facility outreach or personal facility connections and family instrumental support. The mechanisms through which facilitators led to return were: (1) the promising of living out one's life priorities; (2) feeling valued; (3) fostering interpersonal accountability; (4) re-entry navigation support; (5) facilitated care and treatment access; and (6) management of significant barriers, such as depression.

Conclusions

While preliminary, the identified trajectories may guide interventions to support re-engagement, such as offering flexible ART access to patients with intermittent engagement patterns instead of stable patients only. Further, for re-engagement interventions to achieve impact, they must activate mechanisms underlying re-engagement behaviours. For example, facility outreach that reminds a patient to return to care but does not affirm a patient's value or navigate re-entry is unlikely to be effective. The demonstrated importance of positive health facility connections reinforces a growing call for patient-centred care. Additionally, interventions should consider the important role communities play in fostering treatment motivation and overcoming practical barriers.     

Barriers and facilitating factors to the uptake of antiretroviral drugs for prevention of mother-to-child transmission of HIV in sub-Saharan Africa: a systematic review

Objectives

To investigate and synthesize reasons for low access, initiation and adherence to antiretroviral drugs by mothers and exposed babies for prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa.

Methods

A systematic literature review was conducted. Four databases were searched (Medline, Embase, Global Health and Web of Science) for studies conducted in sub-Saharan Africa from January 2000 to September 2012. Quantitative and qualitative studies were included that met pre-defined criteria. Antiretroviral (ARV) prophylaxis (maternal/infant) and combination antiretroviral therapy (ART) usage/registration at HIV care and treatment during pregnancy were included as outcomes.

Results

Of 574 references identified, 40 met the inclusion criteria. Four references were added after searching reference lists of included articles. Twenty studies were quantitative, 16 were qualitative and eight were mixed methods. Forty-one studies were conducted in Southern and East Africa, two in West Africa, none in Central Africa and one was multi-regional. The majority (n=25) were conducted before combination ART for PMTCT was emphasized in 2006. At the individual-level, poor knowledge of HIV/ART/vertical transmission, lower maternal educational level and psychological issues following HIV diagnosis were the key barriers identified. Stigma and fear of status disclosure to partners, family or community members (community-level factors) were the most frequently cited barriers overall and across time. The extent of partner/community support was another major factor impeding or facilitating the uptake of PMTCT ARVs, while cultural traditions including preferences for traditional healers and birth attendants were also common. Key health-systems issues included poor staff-client interactions, staff shortages, service accessibility and non-facility deliveries.

Conclusions

Long-standing health-systems issues (such as staffing and service accessibility) and community-level factors (particularly stigma, fear of disclosure and lack of partner support) have not changed over time and continue to plague PMTCT programmes more than 10 years after their introduction. The potential of PMTCT programmes to virtually eliminate vertical transmission of HIV will remain elusive unless these barriers are tackled. The prominence of community-level factors in this review points to the importance of community-driven approaches to improve uptake of PMTCT interventions, although packages of solutions addressing barriers at different levels will be important.     

Optimizing HIV retesting during pregnancy and postpartum in four countries: a cost‐effectiveness analysis

IntroductionHIV retesting during late pregnancy and breastfeeding can help detect new maternal infections and prevent mother‐to‐child HIV transmission (MTCT), but the optimal timing and cost‐effectiveness of maternal retesting remain uncertain.MethodsWe constructed deterministic models to assess the health and economic impact of maternal HIV retesting on a hypothetical population of pregnant women, following initial testing in pregnancy, on MTCT in four countries: South Africa and Kenya (high/intermediate HIV prevalence), and Colombia and Ukraine (low HIV prevalence). We evaluated six scenarios with varying retesting frequencies from late in antenatal care (ANC) through nine months postpartum. We compared strategies using incremental cost‐effectiveness ratios (ICERs) over a 20‐year time horizon using country‐specific thresholds.ResultsWe found maternal retesting once in late ANC with catch‐up testing through six weeks postpartum was cost‐effective in Kenya (ICER = $166 per DALY averted) and South Africa (ICER=$289 per DALY averted). This strategy prevented 19% (Kenya) and 12% (South Africa) of infant HIV infections. Adding one or two additional retests postpartum provided smaller benefits (1 to 2 percentage point increase in infections averted versus one retest). Adding three retests during the postpartum period averted additional infections (1 to 3 percentage point increase in infections averted versus one retest) but ICERs ($7639 and in Kenya and $11 985 in South Africa) greatly exceeded the cost‐effectiveness thresholds. In Colombia and Ukraine, all retesting strategies exceeded the cost‐effectiveness threshold and prevented few infant infections (up to 31 and 5 infections, respectively).ConclusionsIn high HIV burden settings with MTCT rates similar to those seen in Kenya and South Africa, HIV retesting once in late ANC, with subsequent intervention, is the most cost‐effective strategy for preventing infant HIV infections. In these settings, two HIV retests postpartum marginally reduced MTCT and were less costly than adding three retests. Retesting in low‐burden settings with MTCT rates similar to Colombia and Ukraine was not cost‐effective at any time point due to very low HIV prevalence and limited breastfeeding.     

Population-level analysis of natural control of HIV infection in Zambia and South Africa: HPTN 071 (PopART)

Introduction

HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community-randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013–2018).

Methods

VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non-controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs <2000 with no ARV drugs detected at both visits. Non-controllers who had ARV drugs detected at either visit were excluded from the analysis to minimize potential confounders associated with ARV drug access and uptake.

Results

The final cohort included 126 viraemic controllers and 766 non-controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV-2) status at study enrolment.

Conclusions

To our knowledge, this report presents the first large-scale, population-level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self-reported data). This study identified a large cohort of HIV controllers and non-controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control.     

Antenatal care and uptake of HIV testing among pregnant women in sub-Saharan Africa: a cross-sectional study

Introduction

Current guidelines recommend inclusion of HIV testing in routine screening tests for all pregnant women. For this reason, antenatal care (ANC) represents a vital component of efforts to prevent mother-to-child transmission (PMTCT) of HIV. To elucidate the relationship between ANC services and HIV testing among pregnant women in sub-Saharan Africa, we undertook an analysis of data from four countries.

Methods

Four countries (Congo, Mozambique, Nigeria and Uganda) were purposively selected to represent unique geographical regions of sub-Saharan Africa. Using Demographic and Health Survey datasets, weighted crude and adjusted logistic regression models were used to explore factors that influenced HIV testing as part of ANC services. The study was approved by the Institutional Review Board of the University of Arizona.

Results

Pooled results showed that 60.7% of women received HIV testing as part of ANC. Ugandan women had the highest rate of HIV testing as part of ANC (81.5%) compared with women in Mozambique (69.4%), Nigeria (54.4%) and Congo (45.4%). Difficulty reaching a health facility was a barrier in Congo and Mozambique but not Nigeria or Uganda. HIV testing rates were lower in rural areas, among the poorest women, the least educated and those with limited knowledge of HIV. In every country, crude regression analyses showed higher odds of being tested for HIV if women received their ANC services from a skilled attendant compared with an unskilled attendant. After adjusting for confounders, women in the total sample had 1.78 (99% CI: 1.45–2.18) times the odds of having an HIV test as part of their ANC if they went to a skilled attendant compared with an unskilled attendant.

Conclusions

There is a need for integration of HIV testing into routine ANC service to increase opportunities for PMTCT programmes to reach HIV-positive pregnant women. Attention should be paid to the expansion of outreach services for women in rural settings, and to the training, supervision and integration of unskilled attendants into formal maternal and child health programmes. Education of pregnant women and their communities is needed to increase HIV knowledge and reduce HIV stigma.     

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis

Introduction

In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic.

Methods

A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0–70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2–87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40–0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016–2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016–2020) and the future impact (2021–2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016–2040) of the current PrEP provision.

Results

Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35–0.57%) of HIV infections among FSWs over 2016–2020 or 605 (444–840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99–23.29). PrEP is cost-saving, with $1.42 (1.03–1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572–9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7–11.6%) and impact increases 4.3 times with 24,114 (15,308–38,107) infections averted by 2040.

Conclusions

Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.     

Bidirectional links between HIV and intimate partner violence in pregnancy: implications for prevention of mother-to-child transmission

Introduction

Prevention of mother-to-child transmission (PMTCT) has the potential to eliminate new HIV infections among infants. Yet in many parts of sub-Saharan Africa, PMTCT coverage remains low, leading to unacceptably high rates of morbidity among mothers and new infections among infants. Intimate partner violence (IPV) may be a structural driver of poor PMTCT uptake, but has received little attention in the literature to date.

Methods

We conducted qualitative research in three Johannesburg antenatal clinics to understand the links between IPV and HIV-related health of pregnant women. We held focus group discussions with pregnant women (n=13) alongside qualitative interviews with health care providers (n=10), district health managers (n=10) and pregnant abused women (n=5). Data were analysed in Nvivo10 using a team-based approach to thematic coding.

Findings

We found qualitative evidence of strong bidirectional links between IPV and HIV among pregnant women. HIV diagnosis during pregnancy, and subsequent partner disclosure, were noted as a common trigger of IPV. Disclosure leads to violence because it causes relationship conflict, usually related to perceived infidelity and the notion that women are “bringing” the disease into the relationship. IPV worsened HIV-related health through poor PMTCT adherence, since taking medication or accessing health services might unintentionally alert male partners of the women''s HIV status. IPV also impacted on HIV-related health via mental health, as women described feeling depressed and anxious due to the violence. IPV led to secondary HIV risk as women experienced forced sex, often with little power to negotiate condom use. Pregnant women described staying silent about condom negotiation in order to stay physically safe during pregnancy.

Conclusions

IPV is a crucial issue in the lives of pregnant women and has bidirectional links with HIV-related health. IPV may worsen access to PMTCT and secondary prevention behaviours, thereby posing a risk of secondary transmission. IPV should be urgently addressed in antenatal care settings to improve uptake of PMTCT and ensure that goals of maternal and child health are met in sub-Saharan African settings.