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BACKGROUND: Harmonized population-based surveys with recent HIV-1 infection testing algorithms permit pooled cross-sectional HIV incidence estimation across multiple countries. The objective of this analysis is to estimate adult HIV-1 incidence rates and number of new infections by sex, age, and sub-region in sub-Saharan Africa (SSA). METHODS: We analyzed data from 13 Population-based HIV Impact Assessment (PHIA) surveys and two additional population-based surveys conducted between 2015 and 2019 in 15 SSA countries. HIV-seropositive samples from adults 15-59 years-old were tested for recent HIV-1 infection using an algorithm consisting of the HIV-1 Limiting Antigen Avidity enzyme immunoassay, HIV-1 viral load, and qualitative detection of antiretrovirals. Data were pooled across countries; sampling weights were incorporated to represent all adults in the 15 national populations. Analyses accounted for the complex sample designs. HIV incidence rates (IRs), IR differences, and number of new annual infections were estimated. FINDINGS: Among 445,979 adults sampled, 382 had recent HIV-1 infection. Estimated HIV-1 incidence was 3·3/1,000 PYs (95% CI: 2·6, 4·0) among females and 2·0/1,000 PYs (95% CI: 1·2, 2·7) among males (IR difference: 1.3/1,000 PYs (95% CI: 0.3, 2.3). Among 15-24 year-old adults, the IR was higher for females than males (3·5 versus. 1·2/1,000 PYs; IR difference: 2·3, 95% CI: 0·8, 3·8), but infection rates were comparable between sexes in all other age groups. HIV-1 incidence was 7·4/1,000 PYs (95% CI: 5·0, 9·7) in Southern Africa, 2·3/1,000 PYs (95% CI: 1.7, 2.9) in Eastern Africa, and 0·9/1,000 PYs (95% CI: 0·6, 1·2) in West/Central Africa. Overall, 689,000 (95% CI: 546,000-833,000) new HIV cases were estimated annually among the 265 million susceptible adults—61.6% in females. INTERPRETATION: These findings identify differences in HIV-1 incidence and new infections by age, sex, and sub-region. Approaches for risk stratification are needed to guide comprehensive HIV-1 prevention. FUNDING: National Institutes of Health

Supplemental Material for Two strategies for partner notification and partner HIV self-testing reveal no evident predictors of male partner HIV testing in antenatal settings: A secondary analysis by Andrew Kumwenda, Ann Marie Kathryn Weideman, Lauren Aiko Graybill, Matthew Kevin Dinwiddie, Kellie Freeborn, Mildred M Lusaka, Rose Lungu, Wilbroad Mutale, Nora E Rosenberg, Margaret Kasaro, Katie R. Mollan and Benjamin H Chi in International Journal of STD & AIDS.

Despite considerable progress in maternal healthcare, maternal and perinatal deaths remain high in low-to-middle income countries. Fetal ultrasound is an important component of antenatal care, but shortage of adequately trained healthcare workers has limited its adoption. We developed and validated an artificial intelligence (AI) system that uses novice-acquired "blind sweep" ultrasound videos to estimate gestational age (GA) and fetal malpresentation. We further addressed obstacles that may be encountered in low-resourced settings. Using a simplified sweep protocol with real-time AI feedback on sweep quality, we have demonstrated the generalization of model performance to minimally trained novice ultrasound operators using low cost ultrasound devices with on-device AI integration. The GA model was non-inferior to standard fetal biometry estimates with as few as two sweeps, and the fetal malpresentation model had high AUC-ROCs across operators and devices. Our AI models have the potential to assist in upleveling the capabilities of lightly trained ultrasound operators in low resource settings.

Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context.

IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n=5) and ongoing/planned (n=9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.

Poor HIV care retention impedes optimal treatment outcomes in persons living with HIV. Women trying to become pregnant may be motivated by periconception horizontal and vertical transmission concerns and thus more likely to attend HIV care visits than women not trying to conceive. We estimated the effect of fertility intentions on HIV care attendance over 12 months among non-pregnant, HIV-positive women aged 18–35 years who were on or initiating antiretroviral therapy in Johannesburg, South Africa. The percentage of women attending an HIV care visit decreased from 93.4% in the first quarter to 82.8% in the fourth quarter. Fertility intentions were not strongly associated with care attendance in this cohort of reproductive-aged women; however, attendance declined over time irrespective of childbearing plans. These findings suggest a need for reinforced efforts to support care engagement and risk reduction, including safer conception practices for women wishing to conceive.

BackgroundIMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery.MethodsWomen with pre-ART CD4+ cell counts ≥350cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat.Findings1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27years, CD4+ count 728cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61).InterpretationSerious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

To measure key obstetric and neonatal outcomes recorded at a tertiary hospital in Zambia over a 5-year period.

HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed.

In sub-Saharan Africa, liver disease epidemiology among HIV-infected individuals is not well described, in part due to limited access to diagnostic tests for liver fibrosis.

OBJECTIVE To examine the association between hepatitis B virus (HBV) infection and liver fibrosis in HIV-infected patients in Zambia and Switzerland. METHODS HIV-infected adults starting antiretroviral therapy in two clinics in Zambia and Switzerland were included. Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet-ratio index (APRI), with a ratio >1.5 defining significant fibrosis and a ratio >2.0 indicating cirrhosis. The association between hepatitis B surface antigen (HBsAg) positivity, HBV replication, and liver fibrosis was examined using logistic regression. RESULTS In Zambia, 96 (13.0%) of 739 patients were HBsAg-positive compared to 93 (4.5%) of 2058 in Switzerland. HBsAg-positive patients were more likely to have significant liver fibrosis than HBsAg-negative ones: the adjusted odds ratio (aOR) was 3.25 (95% confidence interval (CI) 1.44-7.33) in Zambia and 2.50 (95% CI 1.19-5.25) in Switzerland. Patients with a high HBV viral load (≥20000 IU/ml) were more likely to have significant liver fibrosis compared to HBsAg-negative patients or patients with an undetectable viral load: aOR 3.85 (95% CI 1.29-11.44) in Zambia and 4.20 (95% CI 1.64-10.76) in Switzerland. In both settings, male sex was a strong risk factor for significant liver fibrosis. CONCLUSIONS Despite the differences in HBV natural history between Sub-Saharan Africa and Europe, the degree of liver fibrosis and the association with important risk factors were similar.

In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services.We offered universal maternal combination antiretroviral regimens in 4 pilot sites in rural Zambia. To evaluate the impact of services, we conducted a household survey in communities surrounding each facility. We collected information about HIV status and antenatal service utilization from women who delivered in the past 2 years. Using household Global Positioning System coordinates collected in the survey, we measured Euclidean (i.e., straight line) distance between individual households and clinics. Multivariable logistic regression and predicted probabilities were used to determine associations between distance and uptake of PMTCT regimens.From March to December 2011, 390 HIV-infected mothers were surveyed across four communities. Of these, 254 (65%) had household geographical coordinates documented. One hundred sixty-eight women reported use of a PMTCT regimen during pregnancy including 102 who initiated a combination antiretroviral regimen. The probability of PMTCT regimen initiation was the highest within 1.9 km of the facility and gradually declined. Overall, 103 of 145 (71%) who lived within 1.9 km of the facility initiated PMTCT versus 65 of 109 (60%) who lived farther away. For every kilometer increase, the association with PMTCT regimen uptake (adjusted odds ratio: 0.90, 95% confidence interval: 0.82 to 0.99) and combination antiretroviral regimen uptake (adjusted odds ratio: 0.88, 95% confidence interval: 0.80 to 0.97) decreased.In this rural African setting, uptake of PMTCT regimens was influenced by distance to health facility. Program models that further decentralize care into remote communities are urgently needed.

In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services.

Although AST-to-platelet ratio index (APRI) and FIB-4 have been compared with liver biopsy in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), HIV/HCV co-infection, and HIV/HBV co-infection, Johannessen and Lemoine stress that they have not been validated in HIV mono-infected populations in SSA. However, this is unlikely to occur because liver biopsy does not play a role in HIV management and the procedure carries its own risks for complication. Clinicians using APRI and FIB-4 in this setting should be aware of this limitation and should interpret test results in the context of each patient's clinical scenario. This article is protected by copyright. All rights reserved.

To reach virtual elimination of pediatric HIV, programs for the prevention of mother-to-child HIV transmission (PMTCT) must expand coverage and achieve long-term retention of mothers and infants. While PMTCT have been traditionally aligned with maternal, newborn, and child health (MNCH) services, novel approaches are needed to address the increasing demands of evolving global PMTCT policies.

Early initiation of antiretroviral therapy (ART) has been shown to reduce mortality among perinatally HIV-infected infants, but availability of virologic testing remains limited in many settings.

To determine the association between the antenatal CD4(+) cell count and the development of viral drug resistance following the use of peripartum nevirapine (NVP) for perinatal HIV prevention.Secondary analysis of data from a previously conducted randomised controlled trial.Lusaka, Zambia.HIV-positive pregnant women.We analysed the data from a clinical trial of single-dose tenofovir/emtricitabine (TDF/FTC) to reduce viral drug resistance associated with peripartum NVP. The trial population was categorised according to antenatal CD4(+) cell count (200-350, 351-500 and500 cells/μl).The relative risk for acquiring drug resistance, determined by consensus sequencing and oligonucleotide ligation assay (OLA), was estimated using multivariable logistic regression.Of the 397 study participants, 119 (30%) had a CD4(+) count of 200-350 cells/μl, 135 (34%) had a CD4(+) count of 351-500 cells/μl and 143 (36%) had a CD4(+) count of500 cells/μl. Among women receiving no intervention, the risk for drug resistance appeared to increase as the CD4(+) cell count decreased. Participants with CD4(+) cell counts of 200-350 cells/μl randomised to the study arm had the lowest risk, suggesting a higher efficacy of the intervention within this stratum. These results were consistent at 2 and 6 weeks, regardless of how drug resistance was measured.Women with CD4(+) cell counts of 200-350 cells/μl may be at increased risk for viral drug resistance following the use of peripartum NVP. Given the high prevalence of NVP resistance and the clear benefits of treatment, antiretroviral therapy should be initiated among pregnant women with CD4(+) cell counts of ≤350 cells/μl.

To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector programme in Lusaka, Zambia.Systematic chart review to retrospectively extract data from medical records of children (i.e.15 years) initiating ART in the Lusaka, Zambia public sector. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis.Between May 2004 and June 2006, 1705 HIV-infected children initiated ART. Of these, 1235 (72%) had their medical records reviewed. Median age at ART initiation was 77 months and 554 (45%) were females. Eight hundred and forty-one (68%) children had an incident condition during this period, with a median time of occurrence of 64 days from ART initiation. Twenty-eight incident conditions were documented. When categorized, the most common were mucocutaneous conditions [incidence rate (IR): 70.6 per 100 child-years, 95% CI: 64.5-77.2] and upper respiratory tract infection (IR: 70.1 per 100 child-years; 95% CI: 64.0-76.7). Children with severe immunosuppression (i.e. CD410%) were more likely to develop lower respiratory tract infection (16.3%vs. 10.2%; P = 0.003) and mucocutaneous conditions (43.9% vs. 35.3%; P = 0.005) than those with CD4or = 10%.There is a high incidence of new illness after ART initiation, emphasizing the importance of close monitoring during this period. Early initiation of ART and use of antimicrobial prophylaxis may also help to reduce the occurrence of such co-morbidities.

To determine the influence of body mass index (BMI) on pregnancy outcomes of HIV-infected and HIV-uninfected Zambian women and to assess the possible role of BMI on mother-to-child transmission rate of HIV.We analysed data from a clinical trial on nevirapine administration for the prevention of mother-to-child transmission of HIV in Lusaka, Zambia. Demographic characteristics, medical information and pregnancy outcomes were used in this secondary analysis.A total of 1211 women were included in this analysis and 36% were HIV-infected. Among HIV-infected women, maternal parity and prior stillbirths increased with increasing BMI in univariate analysis. Mean birth weight rose as well at 28.3 g [95% confidence interval (CI)=14.0-42.6] of infant weight per BMI unit. Transmission of HIV from mother to child appeared inversely related to BMI when compared according to BMI quartile (P for trend=0.07). In the HIV-uninfected group, infant birth weight increased with increasing BMI, at 32.7 g (95% CI=23.5-41.9) of infant weight per BMI unit.Birth weight increased alongside BMI in both HIV-infected and HIV-uninfected women. There is a suggestion that women with lower BMI have a greater risk of perinatal HIV transmission, even after adjustments for HIV viral load and CD4 count.

The purpose of this study was to determine whether the intrauterine contraceptive device (IUD) is effective and safe among women who are infected with the human immunodeficiency virus (HIV).

Over the past decade, services to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have expanded rapidly, resulting in reductions in paediatric acquired immunodeficiency syndrome (AIDS) worldwide.1 However, although an emerging literature demonstrates high maternal HIV incidence during pregnancy and breastfeeding,2 efforts have not focused as much on preventing new infections among pregnant women or their partners. Although recent World Health Organization (WHO) recommendations for pre-exposure prophylaxis are encouraging,3 in sub- Saharan Africa, few – if any – structured interventions are offered to women or their partners during pregnancy and breastfeeding. Most women who access PMTCT care test HIV-negative and for most, engagement in HIV prevention typically ends with individual post-test counselling. To address this gap, we describe a framework to guide HIV prevention efforts for pregnant or breastfeeding women and their partners. This approach considers the unique characteristics of pregnancy, including healthseeking behaviours of women and engagement of male partners, to stratify couples according to HIV transmission and acquisition risk. The approach also leverages the robust infrastructure of existing PMTCT programmes and integrates it within the broader context of general HIV prevention.

BACKGROUND There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analyzed outcomes in cohorts from South Africa, Zambia and Zimbabwe METHODS: Patients aged ≥16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programs in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models. Its parameters were estimated using inverse probability of treatment weights. Baseline characteristics were age, sex, calendar year and country. CD4 cell count, creatinine and hemoglobin levels were included as time-dependent confounders. RESULTS 1,256 patients on second-line ART, including 958 on tenofovir, were analyzed. Patients on tenofovir were more likely to have switched to second-line ART in recent years, spent more time on first-line ART (33 vs. 24 months) and had lower CD4 cell counts (172 vs. 341 cells/μl) at initiation of second-line ART. The adjusted hazard ratio comparing tenofovir with zidovudine was 1.00 (95% confidence interval 0.59-1.68) for virologic failure and 1.40 (0.57-3.41) for death. CONCLUSIONS We did not find any difference in treatment outcomes between patients on tenofovir or zidovudine; however, the precision of our estimates was limited. There is an urgent need for randomized trials to inform second-line ART strategies in resource-limited settings.

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit.

We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia

BackgroundVery few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries.MethodsIn a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts.FindingsBetween 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women.InterpretationWe creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study ({"type":"clinical-trial","attrs":{"text":"NCT00880698","term_id":"NCT00880698"}}NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production.

ObjectivesTo measure the sex-specific and community-specific mortality rates for adults in Lusaka, Zambia, and to identify potential individual-level, household-level and community-level correlates of premature mortality. We conducted 12 survey rounds of a population-based cross-sectional study between 2004 and 2011, and collected data via a structured interview with a household head.SettingHouseholds in Lusaka District, Zambia, 2004–2011.Participants43 064 household heads (88% female) who enumerated 123 807 adult household members aged between 15 and 60 years.Primary outcomePremature adult mortality.ResultsThe overall mortality rate was 16.2/1000 person-years for men and 12.3/1000 person-years for women. The conditional probability of dying between age 15 and 60 (45q15) was 0.626 for men and 0.537 for women. The top three causes of death for men and women were infectious in origin (ie, tuberculosis, HIV and malaria). We observed an over twofold variation of mortality rates between communities. The mortality rate was 1.98 times higher (95% CI 1.57 to 2.51) in households where a family member required nursing care, 1.44 times higher (95% CI 1.22 to 1.71) during the cool dry season, and 1.28 times higher (95% CI 1.06 to 1.54) in communities with low-cost housing.ConclusionsTo meet Zambia's development goals, further investigation is needed into the factors associated with adult mortality. Mortality can potentially be reduced through focus on high-need households and communities, and improved infectious disease prevention and treatment services.

BackgroundFew data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa.MethodsWe enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression.ResultsSeventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.

BACKGROUND The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS We analyzed data from 173,245 patients (61% female, 8% children aged 2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus

Introduction. Although increasing access to family planning has been an important part of the global development agenda, millions of women continue to face unmet need for contraception. Materials and Methods. We analyzed data from a repeated cross-sectional community survey conducted in Lusaka, Zambia, over an eight-year period. We described prevalence of modern contraceptive use, including long-acting reversible contraception (LARC), among female heads of household aged 16–50 years. We also identified predictors of LARC versus short-term contraceptive use among women using modern methods. Results and Discussion. Twelve survey rounds were completed between November 2004 and September 2011. Among 29,476 eligible respondents, 17,605 (60%) reported using modern contraception. Oral contraceptive pills remained the most popular method over time, but use of LARC increased significantly, from less than 1% in 2004 to 9% by 2011 (). Younger women (OR: 0.46, 95% CI: 0.34, 0.61) and women with lower levels of education (OR: 0.70, 95% CI: 0.56, 0.89) were less likely to report LARC use compared to women using short-term modern methods. Conclusions. Population-based assessments of contraceptive use over time can guide programs and policies. To achieve reproductive health equity and reduce unmet contraceptive need, future efforts to increase LARC use should focus on young women and those with less education.

Among 6789 HIV-infected Zambian adults screened for hepatitis B virus (HBV) coinfection, estimated glomerular filtration rate (eGFR) was 50-90 mL/minute/1.73 m(2) in 17.6% and

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts. Methods: We included 18 706 adult patients starting ART in South Africa and 80 937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months. Results: In South Africa, 9.8% [95% confidence interval (CI) 9.1–10.5] had switched at 3 years, 1.3% (95% CI 0.9–1.6) remained on failing first-line regimens, 9.2% (95% CI 8.5–9.8) were lost to follow-up and 4.3% (95% CI 3.9–4.8) had died. In Malawi and Zambia, more patients were on a failing first-line regimen [3.7% (95% CI 3.6–3.9], fewer patients had switched [2.1% (95% CI 2.0–2.3)] and more patients were lost to follow-up [15.3% (95% CI 15.0–15.6)] or had died [6.3% (95% CI 6.0–6.5)]. Median CD4 cell counts were lower in South Africa at the start of ART (93 vs. 132 cells/μl; P

Background Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. Methods We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. Results From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32–7.24 for women, AOR = 3.58, 95 % CI = 2.39–5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51–7.47 for women, AOR = 6.24, 95 % CI = 3.51–11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. Conclusions While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies.

BACKGROUND AND AIMS We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia METHODS: Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunologic status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS Among 20,308 adults in the analysis cohort, 1,027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI

BACKGROUND Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.

We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa.

Background. Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non–TDF-containing ART in Lusaka, Zambia.

Objectives: Fertility intentions and contraceptive use are often not assessed in the context of clinical HIV care, representing a possible programming gap if women's family planning needs change over time. We aimed to identify longitudinal patterns of unmet need for contraception over a 12-month period among women living with HIV taking antiretroviral therapy (ART). Study design: 850 non-pregnant, HIV-positive women aged 18-35 on or initiating ART in Johannesburg, South Africa, were enrolled into a prospective cohort study in 2009-2010. Fertility intentions and contraceptive use were assessed during routine HIV care visits via an interviewer-administered questionnaire, and women were referred for on-site contraceptive counseling. We used group-based trajectory modeling to identify patterns of unmet need for contraception over 12 months, first in the entire population and then in a subset of recent ART initiators. Results: In the full population we identified four patterns of unmet need for contraception over one year. Half of the enrolled women were predicted to have a consistently high probability of unmet need, 22.9% a consistently low probability, 16.7% a decreasing probability, and 10.4% an increasing probability over time. Contraceptive method discontinuation and rapidly changing fertility intentions were the primary drivers of changing (increasing or decreasing) unmet need over follow-up. Results were similar in recent ART initiators. Conclusions: Half of women were estimated to have a high probability of unmet need that persisted over time, and more than a quarter were estimated to experience patterns of changing unmet need over 12 months. Family planning needs should be assessed more regularly in HIV-positive women to prevent unintended pregnancies and support safer conception among women trying to conceive.

Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.