Risa M. Hoffman

Effects of highly active antiretroviral therapy duration and regimen on risk for mother-to-child transmission of HIV in Johannesburg South Africa.

Background:Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression. Methods:Between January 2004 to August 2008, 1142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA polymerase chain reaction at 4-6 weeks) were assessed with multivariate logistic regression. Results:Mean age was 30.2 years (SD = 5.0) and median baseline CD4 count was 161 cells per cubic millimeter (SD = 84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD = 7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD = 37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43 of 874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; P = 0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% confidence interval: 0.87 to 0.99, P = 0.02). Conclusions:Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.

Safety and efficacy of initiating highly active antiretroviral therapy in an integrated antenatal and HIV clinic in Johannesburg, South Africa.

Objective:To describe the safety and efficacy of highly active antiretroviral therapy (HAART) in pregnant women treated in an integrated antiretroviral antenatal clinic (ANC ARV). Methods:A retrospective analysis was performed on patients attending the ANC ARV from August 2004 through February 2007. Results:Data were collected on 689 treatment-naive pregnant women initiated on HAART. The mean age was 29.2 years. The mean baseline CD4+ count was 154 cells per microliter, and mean baseline HIV viral load was 101,561 copies per milliliter. Tuberculosis was the most prevalent presenting opportunistic infection (7.7%). Stavudine, lamivudine, and nevirapine were initiated in 82% of women with the most frequent adverse drug reaction being nevirapine-associated skin rash (3.5%). Mean gestational age at HAART initiation was 27 weeks. Among women with follow-up data, 80% gained 50 or more CD4 cells per microliter and 80.5% achieved viral suppression to <1000 copies per milliliter. Of 302 mother-infant pairs who completed postnatal follow-up, the HIV transmission rate was 5%. In women who received more than 7 weeks of HAART during pregnancy, transmission was 0.3%. Conclusions:Within the ANC ARV program, initiating pregnant women on HAART was feasible, safe, and effective. Advanced gestational age at treatment initiation and loss to follow-up emerge as important challenges in this population.

Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study

BackgroundUse of highly active antiretroviral therapy (HAART), a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development.MethodsOur objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed.ResultsAmong HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART-exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001, respectively).ConclusionsIn this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.

Factors associated with desire for children among HIV-infected women and men: a quantitative and qualitative analysis from Malawi and implications for the delivery of safer conception counseling.

Improved health outcomes have resulted in people with HIV facing decisions about childbearing. We sought to understand the factors associated with desire for a child among men and women in Malawi. HIV-infected men and women ages 18–40 were invited to participate in a brief interview about fertility desires. Single variable logistic regression was used to evaluate the factors associated with the outcome of fertility desire. Additionally, multiple logistic regression was used to assess the relationship of all the factors together on the outcome of fertility desire. In-depth interviews with women were performed to understand experiences with reproductive health care. A total of 202 brief interviews were completed with 75 men (37.1%) and 127 women (62.9%), with 103 (51.0%) of respondents desiring a child. Being in a relationship (OR: 3.48, 95% CI: 1.58–7.65, p = 0.002) and duration of HIV more than two years (OR: 2.00, 95% CI: 1.08–3.67, p = 0.03) were associated with increased odds of desire for a child. Age 36–40 years (OR: 0.64, 95% CI: 0.46–0.90, p = 0.009) and having a living child (OR: 0.24, 95% CI: 0.07–0.84, p = 0.03) were associated with decreased odds of desire for a child. Seventy percent of women (n = 19 of 27 respondents) completing semistructured interviews who responded to the question about decision-making reported that their male partners made decisions about children, while the remainder reported the decision was collaborative (n = 8, 30%). Eighty-six percent of women (n = 36 of 42 respondents) reported no discussion or a discouraging discussion with a provider about having children. HIV-infected women and men in Malawi maintain a desire to have children. Interventions are needed to integrate safer conception into HIV care, to improve male participation in safer conception counseling, and to empower providers to help patients make decisions about reproduction free of discrimination and coercion.

Evaluation of Sex Differences of Fosamprenavir (With and Without Ritonavir) in HIV-Infected Men and Women

Abstract Purpose: Recent studies focusing on HIV-1—infected women have suggested the existence of sex-related differences in natural history, antiretroviral pharmacokinetics, efficacy, and tolerability. This article analyzes three pivotal trials of the protease inhibitor (PI) fosamprenavir (FPV) with a view to providing a better understanding of potential sex differences in efficacy and safety. Method: A post hoc, descriptive analysis was performed on data from 700 subjects (26% women) in three trials of FPV to evaluate sex differences with regard to efficacy, rates of discontinuation, and treatment-related adverse events. Results: No major sex differences were found. Men and women had similarly good antiviral responses, with greater than 60% of treatment-naïve subjects achieving virologic suppression (<400 copies/mL) at 48 weeks. PI-experienced women in CONTEXT receiving once-daily FPV/r experienced the highest rates of discontinuations due to virologic failure (29% in women vs. 8% in men). Women generally had slightly lower rates of liver enzyme elevations and fewer abnormalities of total cholesterol and triglycerides. Conclusion: The absence of major sex differences provides reassurance, but the small number of women in these trials limited the ability to draw conclusions. Future trials should be specifically powered to detect sex differences in safety and efficacy. Key words: antiretroviral efficacy, antiretroviral safety, fosamprenavir, sex differences

Provider attitudes about childbearing and knowledge of safer conception at two HIV clinics in Malawi

BackgroundThere is limited understanding of health care providers’ attitudes towards HIV-infected individuals’ reproductive choices, as well as knowledge about safer conception. Our study objective was to explore provider-level factors that serve as barriers and/or facilitators to the provision of reproductive and safer conception services for men and women living with HIV.MethodsTwenty-five providers were interviewed in four focus group discussions about their attitudes regarding childbearing by HIV-infected clients, reproductive health and HIV knowledge, and views and knowledge of safer conception.ResultsProviders reported ambivalence about supporting childbearing among their clients with HIV. They raised concerns about HIV-infected individuals having children, and in certain cases expressed judgment that people with HIV should not have children because of these concerns. Providers lack specific knowledge about safer conception strategies and have low level of knowledge of reproductive health, the efficacy of PMTCT, and the risks of pregnancy for HIV-infected women.ConclusionsProviders in our setting have complex attitudes about HIV-infected clients having children and lack knowledge to appropriately counsel clients about reproductive health and safer conception. Our findings highlight need for further research in this area as well as the need for provider training in reproductive health and safer conception.

Who Provides Primary Care? An Assessment of HIV Patient and Provider Practices and Preferences

Background Non-AIDS co-morbidities are emerging as the main health problems for those living with HIV, and primary care for this population is an evolving challenge. Recent studies have raised the question of whether specialists or generalists are best suited to provide HIV primary care, but patients’ actual usage patterns and the preferences of patients and providers have not been well studied. Methods We anonymously surveyed 98 patients and eight HIV-specialized providers regarding primary care usage patterns and preferences at an academic HIV clinic in Los Angeles that serves insured patients. Results Fifty-nine percent of patients use their HIV physician as their primary care provider, and 84% would prefer this model. Physicians were divided on their preferred role, with five out of eight desiring to provide both primary care and HIV care. All eight physicians rated their comfort with antiretroviral therapy and opportunistic infections greater than for non-AIDS co-morbidities. Eighty-one percent of patients and seven of eight providers were supportive of having a co-located primary care physician at the HIV clinic. Conclusions We conclude that patients prefer integration of HIV and primary care, but providers have variable desire to serve as primary care physicians and may be uncomfortable with non-AIDS co-morbidities. This raises the need for improved patient-provider communication about primary care needs, and calls for novel ways of systematically providing primary care to HIV-infected patients.

Maternal outcomes after HAART for the prevention of mother―to―child transmission in HIV―infected women in Brazil

BACKGROUND Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. METHODS Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to ≤200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Coxs proportional hazards models. RESULTS A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline ≥500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02). CONCLUSIONS In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.

Bartonella Endocarditis in Complex Congenital Heart Disease

Bartonella species are an important cause of culture-negative endocarditis, with recognized risk factors of alcoholism, homelessness, cat exposure, and pre-existing valvular disease. We report a case of Bartonella henselae endocarditis in a 36-year-old woman with complex congenital heart disease who presented with a 7-month history of hemolytic anemia, leukocytoclastic vasculitis, and recurrent fevers. Transesophageal echocardiogram revealed vegetations on the patients native aortic valve and in the right ventricular to pulmonary artery conduit and associated bioprosthetic valve. Diagnosis of B. henselae was confirmed with serum antibody and polymerase chain reaction (PCR) testing and tissue stains. The patient was treated successfully with surgical resection and prolonged antimicrobial therapy with ceftriaxone, gentamicin, and doxycycline. A review of the literature suggests prosthetic valves and complex congenital heart disease are risk factors for Bartonella endocarditis, and a high index of suspicion with antibody and PCR testing can expedite diagnosis and improve outcomes.

Evaluation of a Structured Predeparture Orientation at the David Geffen School of Medicine's Global Health Education Programs

Given the lack of a standardized approach to medical student global health predeparture preparation, we evaluated an in-person, interactive predeparture orientation (PDO) at the University of California Los Angeles (UCLA) to understand program strengths, weaknesses, and areas for improvement. We administered anonymous surveys to assess the structure and content of the PDO and also surveyed a subset of students after travel on the utility of the PDO. We used Fishers exact test to evaluate the association between prior global health experience and satisfaction with the PDO. One hundred and five students attended the PDO between 2010 and 2014 and completed the survey. One hundred and four students (99.0%) reported learning new information. Major strengths included faculty mentorship (N = 38, 19.7%), opportunities to interact with the UCLA global health community (N = 34, 17.6%), and sharing global health experiences (N = 32, 16.6%). Of students surveyed after their elective, 94.4% (N = 51) agreed or strongly agreed that the PDO provided effective preparation. Students with prior global health experience found the PDO to be as useful as students without experience (92.7% versus 94.4%, P = 1.0). On the basis of these findings, we believe that a well-composed PDO is beneficial for students participating in global health experiences and recommend further comparative studies of PDO content and delivery.