Jaco Homsy

Reproductive Intentions and Outcomes among Women on Antiretroviral Therapy in Rural Uganda: A Prospective Cohort Study

Background Antiretroviral therapy (ART) may influence the biological, social and behavioral determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on ART in Africa. Methodology /Principal Findings Using a prospective cohort design, we analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated ART between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioral questionnaires administered every quarter in year 1 after initiating ART, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting ART. We tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. We modeled repeated measurements of all variables related to the womens desire for children over time using a generalized estimating equation (GEE) extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting ART. During this time, less than 7% of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years (WY) in the first quarter to 9.5 per 100 WY at 24 months (p<0.0001). This was paralleled by an increase in the proportion of women reporting sexual activity in the past 3 months, from 24.4% at baseline to 32.5% over 24 months of follow-up (p = 0.001). Only 14% of women used permanent or semi-permanent family planning methods by their second year on ART. In the multivariate model, younger age (HR = 2.71 per 10-year decrease, 95% CI: 2.95–3.78), having a BMI>18.5 (HR = 1.09, CI: 1.01–1.18) and not having used condoms consistently in the last 3 months (HR = 1.79, CI: 1.02–3.13) were independently associated with pregnancy. Conclusion/Significance Women on ART and their partners should be consistently counseled on the effects of ART in restoring fertility, and offered regularly free and comprehensive family planning services as part of their standard package of care.

Routine intrapartum HIV counseling and testing for prevention of mother-to-child transmission of HIV in a rural Ugandan hospital

Objective: In Africa, prevention of mother-to-child HIV transmission (PMTCT) programs are hindered by limited uptake by women and their male partners. Routine HIV counseling and testing (HCT) during labor has been proposed as a way to increase PMTCT uptake, but little data exist on the impact of such intervention in a programmatic context in Africa. Design and Methods: In May 2004, PMTCT services were established in the antenatal clinic (ANC) of a 200-bed hospital in rural Uganda; in December 2004, ANC PMTCT services became opt-out, and routine opt-out intrapartum HCT was established in the maternity ward. We compared acceptability, feasibility, and uptake of maternity and ANC PMTCT services between December 2004 and September 2005. Results: HCT acceptance was 97% (3591/3741) among women and 97% (104/107) among accompanying men in the ANC and 86% (522/605) among women and 98% (176/180) among their male partners in the maternity. Thirty-four women were found to be HIV seropositive through intrapartum testing, representing an 12% (34/278) increase in HIV infection detection. Of these, 14 received their result and nevirapine before delivery. The percentage of women discharged from the maternity ward with documented HIV status increased from 39% (480/1235) to 88% (1395/1594) over the period. Only 2.8% undocumented women had their male partners tested in the ANC in contrast to 25% in the maternity ward. Of all male partners who presented to either unit, only 48% (51/107) came together and were counseled with their wife in the ANC, as compared with 72% (130/180) in the maternity ward. Couples counseled together represented 2.8% of all persons tested in the ANC, as compared with 37% of all persons tested in the maternity ward. Conclusion: Intrapartum HCT may be an acceptable and feasible way to increase individual and couple participation in PMTCT interventions.

Artemether-Lumefantrine Versus Dihydroartemisinin-Piperaquine for Falciparum Malaria: A Longitudinal, Randomized Trial in Young Ugandan Children

BACKGROUND Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children. METHODS A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year. Children who were at least 4 months of age, weighted at least 5 kg, and had been diagnosed as having their first episode of uncomplicated malaria were randomized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine. The same treatment was given for all subsequent episodes of uncomplicated malaria. Recrudescent and new infections were distinguished by polymerase chain reaction genotyping. Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after randomization. RESULTS A total of 113 children were randomized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine, resulting in 320 and 351 treatments for uncomplicated falciparum malaria, respectively. Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days (35% vs 11%; P = .001]). When the duration of follow-up was extended, differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children randomized to artemether-lumefantrine, compared with those randomized to dihydroartemisinin-piperaquine (4.82 vs 4.61 treatments per person-year; P = .63). The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms. CONCLUSIONS Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria. Clinical trials registration. NCT00527800.

Breastfeeding, mother-to-child HIV transmission, and mortality among infants born to HIV-Infected women on highly active antiretroviral therapy in rural Uganda.

Background:Highly active antiretroviral therapy (HAART) drastically reduces mother-to-child transmission of HIV, but where breastfeeding is the only safe infant feeding option, HAART for the prevention of mother-to-child transmission needs to be evaluated in relation to both HIV transmission and infant mortality. Design and Methods:One hundred and two ≥18-year old women on HAART in rural Uganda who delivered one or more live infants between March 1, 2003 and January 1, 2007 were enrolled in a prospective study to assess HIV transmission and infant survival. All pregnant women were counseled to exclusively breastfeed for 3-6 months according to national guidelines at the time. Infants were followed-up for ≥7 months and were offered HIV polymerase chain reaction testing quarterly from 6 weeks of age until ≥6 weeks after complete weaning. Results:Of 118 infants born during follow-up, 109 (92%) were breastfed. Median durations of exclusive and total breastfeeding were 4 months (interquartile range 3-6) and 5 months (interquartile range 3-7), respectively. None of the infants tested HIV polymerase chain reaction positive over follow-up but 16 infants died without a definitive HIV status at a median age of 2.6 months. In total, 23 (19%) infants died during follow-up at a median age of 3.7 months; 15 (65%) of whom with severe diarrhea and/or vomiting in the week preceding their death. In multivariate analysis, there was a 6-fold greater risk of death among infants breastfed for less than 6 months independent of maternal CD4 count closest to delivery, maternal marital status or maternal death (adjusted hazard ratio = 6.19; 95% confidence interval 1.41-27.0, P = 0.015). Conclusions:In resource-constrained settings, HIV-infected pregnant women should be assessed for HAART eligibility and treated as needed without delay, and should be encouraged to breastfeed their infants for at least 6 months.

Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial

Objective To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa. Design Non-blinded randomised control trial Setting Tororo district, rural Uganda, an area of high malaria transmission intensity Participants 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age Intervention Co-trimoxazole prophylaxis from enrolment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n=185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old. Main outcome measure Incidence of malaria, calculated as the number of antimalarial treatments per person year. Results The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P=0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms. Conclusions Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800

'Pregnancy comes accidentally - like it did with me': reproductive decisions among women on ART and their partners in rural Uganda

BackgroundAs highly active antiretroviral therapy (ART) restores health, fertility and sexual activity among HIV-infected adults, understanding how ART influences reproductive desires and decisions could inform interventions to reduce sexual and vertical HIV transmission risk.MethodsWe performed a qualitative sub-study among a Ugandan cohort of 1,000 adults on ART with four purposively selected categories of participants: pregnant, not pregnant, delivered, and aborted. In-depth interviews examined relationships between HIV, ART and pregnancy, desire for children, perceived risks and benefits of pregnancy, decision-making regarding reproduction and family planning (FP) among 29 women and 16 male partners. Analysis focused on dominant explanations for emerging themes across and within participant groups.ResultsAmong those who had conceived, most couples stated that their pregnancy was unintentional, and often occurred because they believed that they were infertile due to HIV. Perceived reasons for women not getting pregnant included: ill health (included HIV infection and ART), having enough children, financial constraints, fear of mother-to-child HIV transmission or transmission to partner, death of a child, and health education. Most women reported FP experiences with condoms and hormonal injections only. Men had limited FP information apart from condoms.ConclusionsCounselling at ART initiation may not be sufficient to enable women who do not desire children to adopt relevant family planning practices. On-going reproductive health education and FP services, with emphasis on the restoration of fertility after ART initiation, should be integrated into ART programs for men and women.

The need for partner consent is a main reason for opting out of routine HIV testing for prevention of mother-to-child transmission in a rural Ugandan hospital.

Across Africa in 2005 100000 women) can be expected to be infected with HIV. Thus as routine HCT becomes the standard entry point to PMTCT programs understanding the reasons why some women decline the service is increasingly important. (excerpt)

The association between malnutrition and the incidence of malaria among young HIV-infected and -uninfected Ugandan children: a prospective study.

BackgroundIn sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.MethodsA cohort of 100 HIV-unexposed, 203 HIV-exposed (HIV negative children born to HIV-infected mothers) and 48 HIV-infected children aged 6 weeks to 1 year were recruited from an area of high malaria transmission intensity in rural Uganda and followed until the age of 2.5 years. All children were provided with insecticide-treated bed nets at enrolment and daily trimethoprim-sulphamethoxazole prophylaxis (TS) was prescribed for HIV-exposed breastfeeding and HIV-infected children. Monthly routine assessments, including measurement of height and weight, were conducted at the study clinic. Nutritional outcomes including stunting (low height-for-age) and underweight (low weight-for-age), classified as mild (mean z-scores between -1 and -2 during follow-up) and moderate-severe (mean z-scores < -2 during follow-up) were considered. Malaria was diagnosed when a child presented with fever and a positive blood smear. The incidence of malaria was compared using negative binomial regression controlling for potential confounders with measures of association expressed as an incidence rate ratio (IRR).ResultsThe overall incidence of malaria was 3.64 cases per person year. Mild stunting (IRR = 1.24, 95% CI 1.06-1.46, p = 0.008) and moderate-severe stunting (IRR = 1.24, 95% CI 1.03-1.48, p = 0.02) were associated with a similarly increased incidence of malaria compared to non-stunted children. Being mildly underweight (IRR = 1.09, 95% CI 0.95-1.25, p = 0.24) and moderate-severe underweight (IRR = 1.12, 95% CI 0.86-1.46, p = 0.39) were not associated with a significant difference in the incidence of malaria compared to children who were not underweight. There were no significant interactions between HIV-infected, HIV-exposed children taking TS and the associations between malnutrition and the incidence of malaria.ConclusionsStunting, indicative of chronic malnutrition, was associated with an increased incidence of malaria among a cohort of HIV-infected and -uninfected young children living in an area of high malaria transmission intensity. However, caution should be made when making causal inferences given the observational study design and inability to disentangle the temporal relationship between malnutrition and the incidence of malaria.Trial RegistrationClinicalTrials.gov: NCT00527800.

Cost-effectiveness of routine rapid human immunodeficiency virus antibody testing before DNA-PCR testing for early diagnosis of infants in resource-limited settings.

Background: Infants born to HIV-infected women should receive HIV testing to allow early diagnosis and treatment. Recommendations for resource-limited settings stress laboratory-based virologic assays. While effective, these tests are logistically complex and expensive. This study explored the cost-effectiveness of incorporating initial screening with rapid HIV tests (RHT) into the conventional testing algorithm to screen-out HIV-uninfected infants, thereby reducing the need for costly virologic testing. Methods: Data on HIV prevalence, RHT sensitivity and specificity, and costs were collected from 820 HIV-exposed children (1.5–18 months) attending 2 postnatal screening programs in Uganda during July 2005 to December 2006. Cost-effectiveness models compared the conventional testing algorithm DNA polymerase chain reaction (DNA-PCR with Roche Amplicor v1.5) with a modified algorithm (initial RHT to screen-out HIV-uninfected infants before DNA-PCR). Results: The model estimated that the conventional algorithm would identify 94.3% (91.8%–94.7%) of HIV-infected infants, compared with 87.8% (79.4%–90.5%) for a modified algorithm using RHT (HIV 1/2 Determine) and excluding the need for DNA-PCR for HIV antibody-negative infants. Costs per infant were

Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children

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