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In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets. [ABSTRACT FROM AUTHOR]

Background: The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the relevant, non-trial population and is impacted by its eligibility criteria, its organization, and its delivery of the intervention. Here, we compared the outcomes of mortality and hospitalization between an RCT and a cohort study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana.Methods: The Mpepu Study (the RCT) was a clinical trial which determined that co-trimoxazole (CTX) provided no survival benefit for HEUs, allowing both arms of the RCT to be used. The Maikaelelo study (the cohort study) was a prospective observational study that enrolled HEU newborns with telephone follow-up and no in-person visits. Rates of death and hospitalization in the pooled population, were modeled using cox-proportional hazards models for time to death or time to first hospitalization, with study setting (RCT vs. cohort study) as an independent variable. The causal effect of study setting on morbidity and mortality was obtained through a treatment effects approach.Results: In total, 4,010 infants were included; 1,306 were enrolled into the cohort study and 2,704 were enrolled into the RCT. No significant differences in mortality were observed between the two study settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the RCT setting was -0.03 (95% CI: -0.05, -0.01).Conclusions: Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in a cohort study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial. Trial registration The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21). [ABSTRACT FROM AUTHOR]

Background: Rotavirus vaccine (RV) and pneumococcal vaccine (PCV) decrease diarrheal and respiratory disease incidence and severity, but there are few data about the effects of these vaccines among HIV-exposed uninfected (HEU) children. Methods: We recorded RV and PCV vaccination history in a placebo-controlled trial that studied the need for cotrimoxazole among HEU infants in Botswana (the Mpepu Study). We categorized infants by enrollment before or after the simultaneous April 2012 introduction of RV and PCV, and compared diagnoses of diarrhea and pneumonia (grade 3/4), hospitalizations, and deaths from both disease conditions through the 12-month study visit by vaccine era/status across two sites (a city and a village) by Kaplan-Meier estimates. Results: Two thousand six hundred and thirty-five HEU infants were included in this secondary analysis, of these 1689 (64%) were enrolled in Gaborone (344 pre-vaccine, 1345 vaccine) and 946 (36%) in Molepolole (209 pre-vaccine, 737 vaccine). We observed substantial reduction in hazard of hospitalization or death for reason of diarrhea and pneumonia in the vaccine era versus the pre-vaccine era in Molepolole (hazard ratio, HR = 0.44, 95% confidence interval, CI = 0.28, 0.71) with smaller reduction in Gaborone (HR = 0.91, 95% CI = 0.57, 1.45). Similar downward trends were observed for diagnoses of diarrhea and pneumonia separately during the vaccine versus pre-vaccine era. Conclusions: Although temporal confounding cannot be excluded, significant declines in the burden of diarrheal and respiratory illness were observed among HEU children in Botswana following the introduction of RV and PCV. RV and PCV may maximally benefit HEU children in rural areas with higher disease burden. [ABSTRACT FROM AUTHOR]

Background: Phylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions.Methods: We obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013-2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood.Results: We obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2-27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities.Conclusions: A large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018. [ABSTRACT FROM AUTHOR]

Background We sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana. Methods Data and samples were used from the Botswana-based observational Tshipidi study (2010–2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at 18 months of age for anti-CMV immunoglobulin G (IgG). Associations were assessed between detectable anti-CMV IgG and growth (using the World Health Organization Child Growth Standards) and neurodevelopment (using the Bayley Scales of Infant and Toddler Development III and the Developmental Milestones Checklist) at 24 months of age. Results Of 317 children, 215 (68%) had detectable anti-CMV IgG at 18 months of age. Comparatively, 83% (n = 178) of HIV-unexposed uninfected (HUU) children had positive CMV serology vs 47% (n = 139) of HIV-exposed uninfected (HEU) children (P  < .01); 100% of HUU vs 10.5% of HEU children breastfed. Child CMV infection was not associated with weight-for-age, weight-for-length, or length-for-age z-scores at 24 months. In HUU children, CMV infection was associated with smaller head circumference (P  < .01). No difference was observed by child CMV status in any neurodevelopmental domain at 24 months. Conclusions We observed high CMV seropositivity in 18-month-old children in Botswana, with higher seropositivity among breastfed (HUU) children. Positive CMV serostatus was not associated with 24-month child growth or neurodevelopmental outcomes, with the exception of smaller head circumference among HUU CMV-positive children. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early cytomegalovirus (CMV) infection was associated with increased hospitalization rates and decreased vaccine responses in HEU compared with HIV-unexposed (HUU) infants. Methods Among infants enrolled in the Tshipidi study in Botswana, we determined CMV infection status by 6 months of age and compared hospitalization rates and responses to tetanus and Bacille Calmette-Guérin vaccines among HEU and HUU vaccinees. Results Fifteen of 226 (6.6%) HEU infants and 17 (19.3%) of 88 HUU infants were CMV-infected by 6 months. The HEU infants were approximately 3 times as likely to be hospitalized compared with HUU infants (P =.02). The HEU peripheral blood cells produced less interleukin (IL)-2 (P =.004), but similar amounts of interferon-γ, after stimulation with tetanus toxoid. Antitetanus immunoglobulin G titers were similar between groups. Cellular responses to purified protein derivative stimulation did not differ between groups. Maternal receipt of 3-drug antiretroviral therapy compared with zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation. The infants' CMV infection status was not associated with clinical or vaccine response outcomes. Conclusions We observed that increased rates of hospitalization and decreased memory T-cell responses to tetanus vaccine were associated with HIV exposure and incomplete treatment of maternal HIV infection, but not early CMV infection. [ABSTRACT FROM AUTHOR]

Background: Botswana is close to reaching the UNAIDS “90-90-90” HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage. Methods: We used a cross-sectional approach to assessing HIV incidence. A random, population-based sample of adults age 16–64 years was enrolled in 30 rural and peri-urban communities as part of the Botswana Combination Prevention Project (BCPP), from October 2013 –November 2015. Data and samples from the baseline household survey were used to estimate cross-sectional HIV incidence, following an algorithm that combined Limiting-Antigen Avidity Assay (LAg-Avidity EIA), ART status (documented or by testing ARV drugs in plasma) and HIV-1 RNA load. The LAg-Avidity EIA cut-off normalized optical density (ODn) was set at 1.5. The HIV-1 RNA cut-off was set at 400 copies/mL. For estimation purposes, the Mean Duration of Recent Infection was 130 days and the False Recent Rate (FRR) was evaluated at values of either 0 or 0.39%. Results: Among 12,610 individuals participating in the baseline household survey, HIV status was available for 12,570 participants and 3,596 of them were HIV positive. LAg-Avidity EIA data was generated for 3,581 (99.6%) of HIV-positive participants. Of 326 participants with ODn ≤1.5, 278 individuals were receiving ART verified through documentation and were considered to represent longstanding HIV infections. Among the remaining 48 participants who reported no use of ART, 14 had an HIV-1 RNA load ≤400 copies/mL (including 3 participants with ARVs in plasma) and were excluded, as potential elite/viremic controllers or undisclosed ART. Thus, 34 LAg-Avidity-EIA-recent, ARV-naïve individuals with detectable HIV-1 RNA (>400 copies/mL) were classified as individuals with recent HIV infections. The annualized HIV incidence among 16–64 year old adults was estimated at 1.06% (95% CI 0.68–1.45%) with zero FRR, and at 0.64% (95% CI 0.24–1.04%) using a previously defined FRR of 0.39%. Within a subset of younger individuals 16–49 years old, the annualized HIV incidence was estimated at 1.29% (95% CI 0.82–1.77%) with zero FRR, and at 0.90% (95% CI 0.42–1.38%) with FRR set to 0.39%. Conclusions: Using a cross-sectional estimate of HIV incidence from 2013–2015, we found that at the time of near achievement of the UNAIDS 90-90-90 targets, ~1% of adults (age 16–64 years) in Botswana’s rural and peri-urban communities became HIV infected annually. [ABSTRACT FROM AUTHOR]

Mortality in the postpartum period may be impacted by antiretroviral therapy (ART) received in pregnancy, and whether ART is continued in the postpartum period. HIV-infected and HIV-uninfected mothers were enrolled within 48 h of delivery at five public hospital maternity wards throughout Botswana and followed for 24 months. Maternal deaths were reported by one of the approved contacts given by the mother at enrollment. Detailed information on the cause of death was not available. Risk factors for 24-month mortality were assessed using Cox proportional hazard models. From February 2012 to March 2013, 3000 mothers (1499 HIV infected and 1501 HIV uninfected) were enrolled, and 2985 (99.5%) were followed to 24 months or death, or until the death of their child. There were 26 total maternal deaths through 24 months postpartum [439 per 100,000 person-years (p-y)], 22 among HIV-infected women (758 per 100,000 p-y) and 4 among HIV-uninfected women (132 per 100,000 p-y). Maternal HIV-infection (aHR 5.0, 95% CI 1.6-15.2) and infant birth injury (aHR 3.8, 95% CI 1.3-11.4) were independent risk factors for maternal death. Universal ART in pregnancy became the standard-of-care after June 2012, and 978 (65%) women received ART in pregnancy; by 24 months postpartum or end of follow-up, 1148 (79%) had started ART overall. There was no significant difference in 24-month mortality among HIV-infected women who took ART in pregnancy and continued throughout the follow-up period compared with HIV-infected women who took ART or zidovudine in pregnancy and stopped postpartum (aHR 0.6, 95% CI 0.2-1.7). Despite high uptake of ART in pregnancy and postpartum, women with HIV infection in Botswana are five times more likely to die than HIV-uninfected women in the 24 months postpartum. [ABSTRACT FROM AUTHOR]

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Background: The contribution of HIV-exposure to childhood mortality in a setting with widespread antiretroviral treatment (ART) availability has not been determined.Methods: From January 2012 to March 2013, mothers were enrolled within 48 h of delivery at 5 government postpartum wards in Botswana. Participants were followed by phone 1-3 monthly for 24 months. Risk factors for 24-month survival were assessed by Cox proportional hazards modeling.Results: Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58 % received three-drug ART, 23 % received zidovudine alone, 11 % received no antiretrovirals (8 % unknown); 2.1 % of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5 %) children; 106 (3.5 %) died including 12 (38 %) HIV-infected, 70 (4.7 %) HIV-exposed uninfected, and 24 (1.6 %) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95 % CI 10.7, 47.5 %), child HIV-exposure (aHR 2.7, 95 % CI 1.7, 4.5) and maternal death (aHR 8.9, 95 % CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95 % CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26 % maternal HIV prevalence), an estimated 52 % of child mortality occurs among HIV-exposed or HIV-infected children.Conclusions: In a programmatic setting with high maternal HIV prevalence and widespread maternal and child ART availability, HIV-exposed and HIV-infected children still account for most deaths at 24 months. Lack of breastfeeding was a likely contributor to excess mortality among HIV-exposed children. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of knowledge of HIV serostatus on pregnancy intention and contraceptive use in high-HIV-burden southern African settings in the era of widespread antiretroviral treatment availability.Methods: We analyzed interview data collected among 473 HIV-uninfected and 468 HIV-infected pregnant and recently postpartum women at two sites in southern Botswana. Participants were interviewed about their knowledge of their HIV status prior to pregnancy, intendedness of the pregnancy, contraceptive use, and future childbearing desires.Results: The median age of the 941 women was 27 years, median lifetime pregnancies was 2, and 416 (44%) of pregnancies were unintended. Among women reporting unintended pregnancy, 36% were not using a contraceptive method prior to conception. Among contraception users, 81% used condoms, 13% oral contraceptives and 5% an injectable contraceptive. In univariable analysis, women with unintended pregnancy had a higher number of previous pregnancies (P = <0.0001), were less educated (P = 0.0002), and less likely to be married or living with a partner (P < 0.0001). Thirty-percent reported knowing that they were HIV-infected, 48% reported knowing they were HIV-uninfected, and 22% reported not knowing their HIV status prior to conception. In multivariable analysis, women who did not know their HIV status pre-conception were more likely to report their pregnancy as unintended compared to women who knew that they were HIV-uninfected (aOR = 1.7; 95%CI: 1.2-2.5). After controlling for other factors, unintended pregnancy was not associated with knowing one's HIV positive status prior to conception (compared with knowing one's negative HIV status prior to conception). Among women with unintended pregnancy, there was no association between knowing their HIV status and contraceptive use prior to pregnancy in adjusted analyses. Sixty-one percent of women reported not wanting any more children after this pregnancy, with HIV-infected women significantly more likely to report not wanting any more children compared to HIV-uninfected women (aOR = 3.9; 95%CI: 2.6-5.8).Conclusions: The high rates of reported unintended pregnancy and contraceptive failure/misuse underscore an urgent need for better access to effective contraceptive methods for HIV-uninfected and HIV -infected women in Botswana. Lower socioeconomic status and lack of pre-conception HIV testing may indicate higher risk for unintended pregnancy in this setting. [ABSTRACT FROM AUTHOR]

Exclusive breastfeeding has been associated with a reduced risk of late vertical HIV transmission as compared to an infant diet composed of breast milk mixed with supplemental foods or liquids. Hypothesized mechanisms include increased infectivity of breast milk from mothers who practice mixed breastfeeding (MBF), or mechanisms such as increased gastrointestinal permeability in the infant caused by mixed feeding. It has been proposed that MBF may result in subclinical mastitis and higher breast milk HIV titers. However, little is known about the relationship between feeding strategy and breast milk viral load. We measured the HIV-1 concentration in breast milk in a sub-cohort of women enrolled in a mother-to-child HIV transmission prevention trial (the 'Mashi' study). We report no observed relationship between MBF and measured breast milk viral RNA load. Our findings suggest that the increased transmission risk associated with higher breast milk HIV-1 RNA during MBF is unlikely. [ABSTRACT FROM AUTHOR]

Background HIV-exposed but uninfected (HEU) children are at increased risk for poorer growth outcomes compared with HIV-unexposed/uninfected (HUU) children. Mechanisms underlying the poorer growth and delays in development of HEU children compared HUU children are not fully understood. We sought to define the relationship between child CMV status and HIV− exposure status and determine if a correlation existed between CMV status and growth (and neurodevelopmental) outcomes by 24 months of age in Botswana. Methods We used existing data and samples from the observational Botswana Tshipidi study, pregnant women living with HIV (WLHIV) and those without HIV, as well as their infants were enrolled and followed prospectively through 2 years postpartum. We tested 18-month child plasma samples from all available children for anti-HCMV IgG. We evaluated the association between positive (vs. negative) child CMV status at 18 months, and child growth, using the World Health Organization's Growth Standard adjusted for age and sex and neurodevelopment at 24 months of age, using the Bayley Scales of Child Development (BSID) III. Results Of 317 children tested for CMV IgG at 18 months, 215 (67.8%) tested positive. Significantly higher proportions of HUU children had positive CMV serology (82.6%) compared with HEU children (47.4%, P < 0.01); 96.7% of HUU vs. 10.5% of HEU children breastfed. Child CMV infection was not associated with head circumference, weight-for-age, weight-for-height, nor height-for-age z-scores at 24 months. BSID III scores in receptive and expressive language, fine and gross motor, and cognitive domains at 24 months of age also did not differ by child CMV status. Conclusion We observed high rates of CMV seropositivity in 18-month-old children in Botswana with significantly higher CMV seropositivity among HUU children likely owing to breastfeeding. Positive CMV serostatus was not associated with child growth or neurodevelopmental outcomes at 24 months. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women in Botswana. Samples from 752 pregnant women were tested for hepatitis B surface antigen (HBsAg), and HBsAg-positive samples were tested for hepatitis B e antigen (HBeAg) and HBV DNA load. Samples that were HBsAg negative were screened for occult HBV infection by determining the HBV DNA load. HBV genotypes were determined based on a 415-base-pair fragment of the surface gene. Among the 752 women tested during pregnancy or early postpartum, 16 (2.1%) (95% confidence interval (CI): 2.0–2.2) were HBsAg-positive. The prevalence of chronic HBV infection was higher (3.1%) among HIV-infected (95% CI: 3.0–3.2) compared with HIV-uninfected women (1.1%) (95% CI: 1.07–1.1, p = 0.057). Among the 622 HBsAg-negative women, the prevalence of occult HBV infection was 6.6% (95% CI: 6.5–6.7). Three of thirteen HBsAg-positive participants were HBeAg-positive, and all were HIV-negative. Of the 11 maternal samples successfully genotyped, five (45.5%) were genotype D3, five (45.5%) were genotype A1, and one was genotype E (9%). Low and similar proportions of HIV-infected and -uninfected pregnant women in Botswana had occult or chronic HBV infection. We identified a subset of HIV-negative pregnant women who had high HBV DNA levels and were HBeAg-positive, and thus likely to transmit HBV to their infants. [ABSTRACT FROM AUTHOR]

Background: To reduce risk of antiretroviral resistance when stopping efavirenz (EFV)-based antiretroviral treatment (ART), staggered discontinuation of antiretrovirals (an NRTI tail) is recommended. However, no data directly support this recommendation. Objectives: We evaluated the prevalence of HIV drug resistance mutations in pregnant women living with HIV who stopped efavirenz (EFV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) postpartum. Method: In accordance with the prevailing Botswana HIV guidelines at the time, women with pre-treatment CD4 > 350 cells/mm3, initiated EFV/FTC/TDF in pregnancy and stopped ART at 6 weeks postpartum if formula feeding, or 6 weeks after weaning. A 7-day tail of FTC/TDF was recommended per Botswana guidelines. HIV-1 RNA and genotypic resistance testing (bulk sequencing) were performed on samples obtained 4–6 weeks after stopping EFV. Stanford HIV Drug Resistance Database was used to identify major mutations. Results: From April 2014 to May 2015, 74 women who had stopped EFV/FTC/TDF enrolled, with median nadir CD4 of 571 cells/mm3. The median time from cessation of EFV to sample draw for genotyping was 5 weeks (range: 3–13 weeks). Thirty-two (43%) women received a 1-week tail of FTC/TDF after stopping EFV. HIV-1 RNA was available from delivery in 70 (95%) women, 58 (83%) of whom had undetectable delivery HIV-1 RNA (< 40 copies/mL). HIV-1 RNA was available for 71 women at the time of genotyping, 45 (63%) of whom had HIV-1 RNA < 40 copies/mL. Thirty-five (47%) of 74 samples yielded a genotype result, and four (11%) had a major drug resistance mutation: two with K103N and two with V106M. All four resistance mutations occurred among women who did not receive an FTC/TDF tail (4/42, 10%), whereas no mutations occurred among 18 genotyped women who had received a 1-week FTC/TDF tail (p = 0.053). Conclusions: Viral rebound was slow following cessation of EFV/FTC/TDF in the postpartum period. Use of an FTC/TDF tail after stopping EFV was associated with the lower prevalence of subsequent NNRTI drug resistance mutation. [ABSTRACT FROM AUTHOR]

Background: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.Methods: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals.Results: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35).Conclusions: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.). [ABSTRACT FROM AUTHOR]

Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV) or nevirapine (NVP) prophylaxis for the prevention of intrapartum mother-to-child HIV transmission (MTCT) among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants. Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS) Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation), with a birth weight = 2500 g and who were formula-fed from birth. ZDV infant prophylaxis was used from Mpepu Study inception. A protocol modification mid-way through the study led to the subsequent use of NVP infant prophylaxis. Results: Among infants qualifying for this secondary retrospective analysis, a total of 695 (52%) infants received ZDV, while 646 (48%) received NVP from birth for at least 25 days but no more than 35 days. Confirmed intrapartum HIV infection occurred in two (0.29%) ZDV recipients and three (0.46%) NVP recipients (p = 0.68). Anaemia occurred in 19 (2.7%) ZDV versus 12 (1.9%) NVP (p = 0.36) recipients. Neutropenia occurred in 28 (4.0%) ZDV versus 21 (3.3%) NVP recipients (p = 0.47). Conclusions: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4) among formula-fed full-term infants with a birthweight ≥ 2500 g. [ABSTRACT FROM AUTHOR]

The article presents a study on the effect of highly active antiretroviral therapy (HAART) on the growth of HIV-uninfected infants in Botswana. It states that HIV-infected pregnant women from four sites in Botswana and HIV-uninfected infants were the subjects of the study. The study use the World Health Organization Child Growth Standards to calculate the growth of the infants. It concludes that the lower weights on HAART-exposed uninfected infants can be corrected in the first six months of life.

BACKGROUND: We sought to determine if HIV-exposed uninfected (HEU) children had worse neurodevelopmental outcomes at 24 months compared with HIV-unexposed uninfected (HUU) children in Botswana. METHODS: HIV-infected and uninfected mothers enrolled in a prospective observational study ("Tshipidi") in Botswana from May 2010 to July 2012. Child neurodevelopment was assessed at 24 months with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III: cognitive, gross motor, fine motor, expressive language, and receptive language domains) and the Development Milestones Checklist (DMC), a caregiver-completed questionnaire (locomotor, fine motor, language and personal-social domains). We used linear regression models to estimate the association of in-utero HIV exposure with neurodevelopment, adjusting for socioeconomic and maternal health characteristics. RESULTS: We evaluated 670 children (313 HEU, 357 HUU) with ≥1 valid Bayley-III domain assessed and 723 children (337 HEU, 386 HUU) with a DMC. Among the 337 HEU children with either assessment, 122 (36%) were exposed in utero to maternal 3-drug antiretroviral treatment and 214 (64%) to zidovudine. Almost all HUU children (99.5%) breastfed, compared with only 9% of HEU children. No domain score was significantly lower among HEU children in adjusted analyses. Bayley-III cognitive and DMC personal-social domain scores were significantly higher in HEU children than in HUU children, but differences were small. CONCLUSIONS: HEU children performed equally well on neurodevelopmental assessments at 24 months of age compared with HUU children. Given the global expansion ofthe HEU population, results suggesting no adverse impact of in-utero HIV and antiretroviral exposure on early neurodevelopment are reassuring. [ABSTRACT FROM AUTHOR]