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1.
Artigo em Inglês | MEDLINE | ID: mdl-32195745

RESUMO

BACKGROUND: A large-scale evaluation of mother-to-child transmission (MTCT) with dolutegravir (DTG)-based antiretroviral treatment (ART) has not been conducted previously. SETTING: Botswana was the first African country to change from efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC) to DTG/TDF/FTC first-line ART. METHODS: From April 2015-July 2018, the Early Infant Treatment Study offered HIV DNA testing at <96 hours of life. Maternal ART regimen was available for screened infants who could be linked to the separate Tsepamo surveillance study database. We evaluated characteristics of HIV-positive infants, and compared MTCT rates by ART regimen for linked infants. RESULTS: Of 10,622 HIV-exposed infants screened, 42 (0.40%) were HIV-positive. In total, 5,064 screened infants could be linked to the surveillance database, including 1,235 (24.4%) exposed to DTG/TDF/FTC and 2,411 (47.6%) exposed to EFV/TDF/FTC. MTCT was rare when either regimen was started prior to conception: 0/213 (0.00%, 95% CI: 0.00%, 1.72%) on DTG, 1/1,497 (0.07%, 95% CI: 0.00%, 0.37%) on EFV. MTCT was similar for women starting each ART regimen in pregnancy: 8/999 (0.80%, 95% CI: 0.35%, 1.57%) for DTG and 8/883 (0.91%, 95% CI: 0.39%, 1.78%) for EFV (risk difference 0.11%, 95% CI: -0.79%, 1.06%). Most MTCT events (4/8 with DTG, 6/9 with EFV) occurred when ART was started <90 days before delivery. Infants exposed to DTG in utero had lower baseline HIV RNA compared with other HIV-infected infants. CONCLUSION: In utero MTCT in Botswana remains rare in the DTG era. No significant MTCT differences were observed between DTG/TDF/FTC and EFV/TDF/FTC. Risk was highest for both groups when ART was started in the 3 trimester.

2.
J Int AIDS Soc ; 23(2): e25455, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32091179

RESUMO

INTRODUCTION: Achieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign. DISCUSSION: These three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured. CONCLUSIONS: These trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

3.
Clin Infect Dis ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927562

RESUMO

BACKGROUND: Early antiretroviral treatment (ART) is recommended for HIV-infected infants. However, few antiretroviral options are available for neonates. METHODS: The Early Infant Treatment Study in Botswana tested HIV-exposed infants using DNA PCR within 96 hours of birth, and HIV-infected infants started nevirapine (NVP) 6mg/kg BID, zidovudine (ZDV), and lamivudine (3TC) at age <7 days. Nevirapine trough concentrations were tested at 1 and 2 weeks. NVP was switched to lopinavir-ritonavir (LPV-r) at week 2, 3, 4, or 5 according to delivery gestational age (≥38, 37, 36, 35 weeks). RESULTS: Forty HIV-infected infants started ART at median age 2 days (range 1-5). Nevirapine trough concentrations were highly variable and below therapeutic target (3000ng/mL) for 50% of 2-week measurements; concentrations did not correlate with viral decline at weeks 2, 4, or 12. Two deaths unrelated to ART occurred through 24 weeks. Only one unscheduled treatment modification was required. Within 4 weeks of transition to LPV-r, 9 (22.5%) had transient HIV RNA increases, likely due to poor LPV-r palatability. At 12 weeks, HIV-1 RNA was <40 copies/mL for 22 (55%) of 40 (93% <400 copies/mL); by 24 weeks, 27 (71%) of 38 were <40 copies/mL (84% <400 copies/mL). HIV-1 RNA response at 12 and 24 weeks did not differ by baseline HIV RNA, or other factors. CONCLUSIONS: NVP/ZDV/3TC started in the first week of life was safe and effective, even when trough NVP levels were below target. Transient viral increases occurred following transition to LPV-r, but by 12 and 24 weeks most children achieved and maintained viral suppression.

4.
J Int AIDS Soc ; 22(12): e25428, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31850683

RESUMO

INTRODUCTION: Antiretroviral therapy (ART) has significantly improved survival in Africa in recent years. In Botswana, where adult HIV prevalence is 21.9%, AIDS-related mortality is estimated to have declined by 58% between 2005 and 2013 following the initial wide-spread introduction of ART, and ART coverage has steadily increased reaching 84% in 2016. However, there remains little data about the burden of HIV and its impact on mortality in the hospital setting where most deaths occur. We aimed to describe the burden of HIV and related morbidity and mortality among hospitalized medical patients in a district hospital in southern Botswana in the era of widespread ART coverage. METHODS: We prospectively reviewed medical admissions to Scottish Livingstone Hospital from December 2015 to November 2017 and recorded HIV status, demographics, clinical characteristics and final diagnoses at discharge, death or transfer. We ascertained outcomes and determined factors associated with mortality. Results were compared with similar surveillance data collected at the same facility in 2011 to 2012. RESULTS: A total of 2316 admissions occurred involving 1969 patients; 42.4% were of HIV-positive patients, 46.9% of HIV-negative patients and 10.7% of patients with unknown HIV status. Compared to HIV-negative patients, HIV-positive patients had younger age (mean 42 vs. 64 years, p < 0.0001) and higher mortality (22.2% vs. 18.0%, p = 0.03). Tuberculosis was the leading diagnosis among mortality cases in both groups but accounted for a higher proportion of deaths among HIV-positive admissions (44.5%) compared with HIV-negative admissions (19.4%, p < 0.0001). Compared with similar surveillance in 2011 to 2012, HIV prevalence was lower (42.4% vs. 47.6%, p < 0.01), and among HIV-positive admissions: ART coverage was higher (72.2% vs. 56.2%, p < 0.0001), viral load suppression was similar (78.6% vs. 80.3%, p = 0.77), CD4 counts were higher (55.0% vs. 44.6% with CD4 ≥200 cells/mm3 , p < 0.001), mortality was similar (22.2 vs. 22.7%, p = 0.93), tuberculosis diagnoses increased (27.5% vs. 20.1%, p < 0.01) and tuberculosis-associated mortality was higher (35.9% vs. 24.7%, p = 0.05). CONCLUSIONS: Despite high ART-coverage in Botswana, HIV-positive patients continue to be disproportionately represented among hospital admissions and deaths. Deaths from tuberculosis may be contributing to lack of reduction in inpatient mortality. Our findings suggest that control of HIV and tuberculosis remain top priorities for reducing inpatient mortality in Botswana.

5.
J Infect Dis ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31711179

RESUMO

BACKGROUND: HIV-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early 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 BCG 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. HEU infants were nearly 3 times as likely to be hospitalized compared with HUU infants (p=0.02). HEU peripheral blood cells produced less IL-2 (p=0.004), but similar amounts of IFNγ, following stimulation with tetanus toxoid. Anti-tetanus IgG titers were similar between groups. Cellular responses to PPD 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. 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.

6.
Medicine (Baltimore) ; 98(47): e18014, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764816

RESUMO

RATIONALE: Early initiation of antiretroviral therapy (ART) leads to long-term viral suppression, reduces proviral reservoir size, and prolongs time to rebound. Since human immunodeficiency virus (HIV) is a lifelong disease, diagnostic monitoring after confirmed infection is typically not performed; therefore, little is known about the impact of early initiation and long-term ART on the sensitivity of assays that detect HIV antibodies and viral nucleic acid in children and adolescents. PATIENT CONCERNS: Here we report 1 case of diagnosed and confirmed perinatal HIV-1C infection with longstanding viral suppression, who subsequently had a negative HIV-1 deoxyribonucleic acid (DNA) test, undetectable antibodies to HIV-1, and high CD4+ T cell count after 14 years of ART. DIAGNOSIS: The patient was diagnosed with HIV in 2002 at 1 and 2 months of age using DNA polymerase chain reaction. At 8 months old, his viral load was 1210 HIV ribonucleic acid (RNA) copies/mL and CD4 T cell count was 3768 cells/mm. INTERVENTION: At the age of 9 months, highly active antiretroviral therapy comprising of zidovudine, nevirapine, and lamivudine was initiated. The patient remained on this treatment for 14 years 11 months and was virally suppressed. OUTCOMES: At the age of 14 years 4 months, the participant decided to visit a local voluntary HIV testing center, where a rapid HIV test came out negative and the viral load was undetectable (<400 HIV-1 RNA copies/mL). These results led to termination of ART which led to viral rebound within 9 months. LESSONS: As more people with early HIV infection initiate early ART in the context of "Test and Treat all" recommendations, aspects of this report may become more commonplace, with both clinical and public health implications. If the possibility of functional cure (or false-positive diagnosis) is being considered, decisions to terminate ART should be made cautiously and with expert guidance, and may benefit from highly sensitive quantification of the proviral reservoir.


Assuntos
Terapia Antirretroviral de Alta Atividade , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Provírus/genética , Ativação Viral , Adolescente , Seguimentos , Humanos , Recém-Nascido , Masculino , Fatores de Tempo , Suspensão de Tratamento
7.
PLoS One ; 14(11): e0225076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765394

RESUMO

INTRODUCTION: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. METHODS: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. RESULTS: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16-24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. CONCLUSIONS: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely.

9.
Sci Transl Med ; 11(520)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776292

RESUMO

Neonatal HIV-1 infection is associated with rapidly progressive and frequently fatal immune deficiency if left untreated. Immediate institution of antiretroviral therapy (ART), ideally within hours after birth, may restrict irreversible damage to the developing neonatal immune system and possibly provide opportunities for facilitating drug-free viral control during subsequent treatment interruptions. However, the virological and immunological effects of ART initiation within hours after delivery have not been systematically investigated. We examined a unique cohort of neonates with HIV-1 infection from Botswana who started ART shortly after birth and were followed longitudinally for about 2 years in comparison to control infants started on treatment during the first year after birth. We demonstrate multiple clear benefits of rapid antiretroviral initiation, including an extremely small reservoir of intact proviral sequences, a reduction in abnormal T cell immune activation, a more polyfunctional HIV-1-specific T cell response, and an innate immune profile that displays distinct features of improved antiviral activity and is associated with intact proviral reservoir size. Together, these data offer rare insight into the evolutionary dynamics of viral reservoir establishment in neonates and provide strong empirical evidence supporting the immediate initiation of ART for neonates with HIV-1 infection.

10.
J Int AIDS Soc ; 22(9): e25372, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31529598

RESUMO

INTRODUCTION: To adequately ascertain drug safety and efficacy, drug trials need to include participants from all groups likely to receive the medication following approval. Pregnant women, however, are mostly excluded from trials, and women participating are often required to use highly effective contraception and taken off study product (even off study) if they conceive. There is little commercial incentive for including pregnant women in clinical trials, even when preclinical animal and human pharmacokinetic and safety data appear reassuring. With this conservative approach, large numbers of pregnant women are exposed to drug postlicensing with little known about drug safety and efficacy, and little done to systematically monitor outcomes of pregnancy exposure. DISCUSSION: The article focuses on antiretrovirals for treating and preventing HIV, and presents potential approaches which could extend to other therapeutic areas, to obtaining adequate and timely data to inform use of these drugs in this population. Most importantly the pregnancy risk profile of investigational agents can be systematically stratified from low to high risk, based on guidelines from regulatory bodies. This stratification can determine the progress through preclinical work with animals and non-pregnant women to opportunistic studies among women who become pregnant on a clinical trial or within routine clinical treatment. Stratification can include pregnant women in clinical trials, concurrent with Phase II/III trials in non-pregnant adults, and ultimately to postmarketing surveillance for outcomes in pregnant women and their infants. Each step can be enabled by clear criteria from international and local regulatory bodies on progression through study phases, standardized protocols for collecting relevant data, collaborative data sharing, pregnancy outcomes surveillance systems supported by committed funding for these endeavours. CONCLUSIONS: A formalized step-wise approach to including pregnant women in antiretroviral drug research should become the new norm. Systematic implementation of this approach would yield more timely and higher quality pregnancy dosing, safety and efficacy data. Through more vigorous action, regulatory bodies could responsibly overcome reluctance to include pregnant women in drug trials. Funders, researchers and programme implementers need to be galvanized to progressively include pregnant women in research - the use of newer, more effective drugs in women is at stake (349).

11.
JCI Insight ; 4(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31487271

RESUMO

We hypothesized that HIV-1 with dual-class but not single-class drug resistance mutations linked on the same viral genome, present in the virus population before initiation of antiretroviral therapy (ART), would be associated with failure of ART to suppress viremia. To test this hypothesis, we utilized an ultrasensitive single-genome sequencing assay that detects rare HIV-1 variants with linked drug resistance mutations (DRMs). A case (ART failure) control (nonfailure) study was designed to assess whether linkage of DRMs in pre-ART plasma samples was associated with treatment outcome in the nevirapine/tenofovir/emtricitabine arm of the AIDS Clinical Trials Group A5208/Optimal Combined Therapy After Nevirapine Exposure (OCTANE) Trial 1 among women who had received prior single-dose nevirapine. Ultrasensitive single-genome sequencing revealed a significant association between pre-ART HIV variants with DRMs to 2 drug classes linked on the same genome (dual class) and failure of combination ART with 3 drugs to suppress viremia. In contrast, linked, single-class DRMs were not associated with ART failure. We conclude that linked dual-class DRMs present before the initiation of ART are associated with ART failure, whereas linked single-class DRMs are not.

12.
Curr Opin HIV AIDS ; 14(6): 442-448, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31449090

RESUMO

PURPOSE OF REVIEW: Botswana, a small country in southern Africa, has had a very high prevalence of HIV since about 1995. It seems important to analyze the response of this country to help us understand how it became one of the first nations to achieve the 90-90-90 targets. RECENT FINDINGS: Botswana began a national program for treatment of HIV/AIDS with ARVs in 2002. Initially established in the four largest population centers, it expanded to more than 30 sites throughout the country by 2004. Also in 2004, an 'opt out' system for HIV testing was introduced. The government-sponsored ARV regimen for initiation was ZDV/3TC/EFV until 2008, then TDF/FTC/EFV until 2016, when it became TDF/FTC/DTG along with the introduction of treatment for all. Levels of both acquired and transmitted drug resistance have been low. In late 2013, we began the Ya Tsie or Botswana Combination Prevention Project (BCCP), a cluster randomized trial for 100 000 exurban and rural adults in 30 villages that included enhanced testing, linkage to care, and ARV treatment for 15 intervention villages, one in each pair. A 20% baseline survey in 2013-2015 revealed 29% prevalence and values that were already close to 90-90-90. With 83.3% of HIV-positive adults knowing they were infected, 87.4% of those knowing they were infected already on ARV, and 96.5% of those on ARV in complete viral suppression, this represented a combined value of 70.2% toward the target of 73%. By best estimates, incidence fell by about 30% over the 29-month period of the trial, which is compatible with Botswana reaching a 90% reduction in incidence in 10 years as proposed by the UNAIDS model. On the basis of an end-of-study survey in three intervention villages, we estimate that Botswana could reach 95-95-95 by 2019. SUMMARY: These results illustrate that it is possible to reach 90-90-90 in countries with very high HIV prevalence.

13.
AIDS Care ; : 1-7, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31298037

RESUMO

We conducted a qualitative study using focus groups and in-depth interviews to explore barriers to and facilitators of linkage-to-care and antiretroviral treatment (ART) initiation in Botswana. Participants were selected from communities receiving interventions through the Ya Tsie Study. Fifteen healthcare providers and 49 HIV-positive individuals participated. HIV-positive participants identified barriers including stigma, discrimination and overcrowded clinics, and negative staff attitudes; personal factors, such as a lack of acceptance of one's HIV status, non-disclosure, and gender differences; along with lack of social/family support, and certain religious beliefs. Healthcare providers cited delayed test results, poverty, and transport difficulties as additional barriers. Major facilitators were support from healthcare providers, including home visits, social support, and knowing the benefits of ART. Participants were highly supportive of universal ART as a personal health measure. Our results highlighted a persistent structural health facility barrier: HIV-positive patients expressed strong discontent with HIV care/treatment being delivered differently than routine healthcare, feeling inconvenienced and stigmatized by separately designated locations and days of service. This barrier was particularly problematic for highly mobile persons. Addressing this structural barrier, which persists even in the context of high ART uptake, could bring gains in willingness to initiate ART and improved adherence in Botswana and elsewhere.

14.
J Acquir Immune Defic Syndr ; 81(5): e135-e140, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31295173

RESUMO

BACKGROUND: Little is known about the combined impact of HIV/syphilis coinfection on birth outcomes. METHODS: Antenatal HIV and syphilis test results, obstetric history, and infant birth outcomes were collected from obstetric records in maternity wards in Botswana between 2008 and 2011 (5 sites) and 2014 and 2016 (8 sites). We used logistic regression to compare adverse birth outcomes by HIV and syphilis status. Outcomes included stillbirth, preterm delivery, low birth weight, and in-hospital neonatal death. RESULTS: Of 76,466 women, 75,770 (99.1%) had HIV test results, and 20,520 (27.1%) were HIV positive. Syphilis test results were available for 67,290 (88.0%), and 697 (1.0%) had reactive rapid plasma reagin. Among 692 women with syphilis and an HIV test result, 261 (37.7%) were coinfected. HIV-infected women were more likely to be infected with syphilis than HIV-uninfected women [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.44 to 1.96]. From 2008-2011 to 2014-2016, the proportion of women with syphilis remained constant (1.1% vs. 1.0%, P = 0.41), but HIV/syphilis coinfection declined from 45% to 27% (P < 0.0001). Stillbirth occurred in 5.8% of coinfected women, compared with 1.9% with no HIV/syphilis (OR = 3.09; 95% CI: 1.83 to 5.23); 3.4% with HIV alone (OR = 1.75; 95% CI: 1.03 to 2.97), or 3.7% with syphilis alone (OR = 1.58; 95% CI: 0.77 to 3.25). Low birth weight occurred in 24.1% of coinfected women, compared with 12.1% with no HIV/syphilis (OR 2.31; 95% CI: 1.74 to 3.08; 20% with HIV alone (OR = 1.27; 95% CI: 0.96 to 1.69); or 14.6% with syphilis alone (OR = 1.85; 95% CI: 1.26 to 2.74). CONCLUSIONS: Although HIV/syphilis coinfection in pregnancy has declined in the past decade, coinfection was associated with adverse birth outcomes.

15.
Lancet HIV ; 6(8): e552-e558, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307946

RESUMO

Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10-19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.

16.
South Afr J HIV Med ; 20(1): 899, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308965

RESUMO

Background: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. Objectives: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities. Methods: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. Results: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44-1.80), intergenerational sex (PR 9.00; 95% CI 5.84-13.88) and transactional sex (PR 3.46; 95% CI 2.07-5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41-0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45-0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57-0.74). Conclusions: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming.

17.
N Engl J Med ; 381(3): 230-242, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31314967

RESUMO

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.).


Assuntos
Antirretrovirais/uso terapêutico , Circuncisão Masculina , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Programas de Rastreamento , Adolescente , Adulto , Botsuana/epidemiologia , Circuncisão Masculina/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Incidência , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , População Rural , Fatores Socioeconômicos , Carga Viral , Adulto Jovem
18.
N Engl J Med ; 381(9): 827-840, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31329379

RESUMO

BACKGROUND: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies. METHODS: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87). CONCLUSIONS: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).


Assuntos
Antirretrovirais/efeitos adversos , Anormalidades Congênitas/epidemiologia , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Botsuana/epidemiologia , Quimioterapia Combinada , Feminino , Feto/efeitos dos fármacos , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Recém-Nascido , Defeitos do Tubo Neural/epidemiologia , Vigilância da População , Gravidez , Prevalência , Fatores Socioeconômicos
19.
PLoS One ; 14(6): e0218094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170274

RESUMO

PURPOSE: Men in Botswana present with more advanced cancer than women, leading to poorer outcomes. We sought to explain sex-specific differences in time to and stage at treatment initiation. METHODS: Cancer patients who initiated oncology treatment between October 2010 and June 2017 were recruited at four oncology centers in Botswana. Primary outcomes were time from first visit with cancer symptom to treatment initiation, and advanced cancer (stage III/IV). Sociodemographic and clinical covariates were obtained retrospectively through interviews and medical record review. We used accelerated failure time and logistic models to estimate standardized sex differences in treatment initiation time and risk differences for presentation with advanced stage. Results were stratified by cancer type (breast, cervix, non-Hodgkin's lymphoma, anogenital, head and neck, esophageal, other). RESULTS: 1886 participants (70% female) were included. After covariate adjustment, men experienced longer excess time from first presentation to treatment initiation (8.4 months) than women (7.0 months) for all cancers combined (1.4 months, 95% CI: 0.30, 2.5). In analysis stratified by cancer type, we only found evidence of a sex disparity (Men: 8.2; Women: 6.8 months) among patients with other, non-common cancers (1.4 months, 95% CI: 0.01, 2.8). Men experienced an increased risk of advanced stage (Men: 67%; Women: 60%; aRD: 6.7%, 95% CI: -1.7%, 15.1%) for all cancers combined, but this disparity was only statistically significant among patients with anogenital cancers (Men: 72%; Women: 50%; aRD: 22.0%, 95% CI: 0.5%, 43.5%). CONCLUSIONS: Accounting for the types of cancers experienced by men and women strongly attenuated disparities in time to treatment initiation and stage. Higher incidence of rarer cancers among men could explain these disparities.


Assuntos
Disparidades em Assistência à Saúde , Neoplasias/diagnóstico , Neoplasias/terapia , Adulto , Idoso , Botsuana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
20.
Am J Epidemiol ; 188(9): 1674-1681, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31107529

RESUMO

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias.

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