Vivian Black

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.

High Pregnancy Intentions and Missed Opportunities for Patient–Provider Communication About Fertility in a South African Cohort of HIV-Positive Women on Antiretroviral Therapy

High fertility intentions amongst HIV-positive women have been reported elsewhere. Less is known about how clinical and HIV treatment characteristics correlate with fertility intentions. We use cross-sectional baseline data from a prospective cohort study to assess pregnancy intentions and patient–provider communication around fertility. Non-pregnant, HIV-positive women aged 18–35 on ART were recruited through convenience sampling at Johannesburg antiretroviral (ART) treatment facilities. Among the 850 women in this analysis, those on efavirenz had similar fertility intentions over the next year as women on nevirapine-based regimens (33% vs. 38%). In multivariate analysis, recent ART initiation was associated with higher current fertility intentions; there was no association with CD4 cell count. Forty-one percent of women had communicated with providers about future pregnancy options. Women on ART may choose to conceive at times that are sub-optimal for maternal, child and partner health outcomes and should be routinely counseled around safer pregnancy options.

Effect of human immunodeficiency virus treatment on maternal mortality at a tertiary center in South Africa: a 5-year audit.

OBJECTIVE: To review facility-based maternal deaths at a tertiary-level center in Johannesburg, South Africa, during a 5-year period (2003 to 2007) and to investigate the proportion of deaths attributable to human immunodeficiency virus (HIV), the etiology of deaths, and the effects of antiretroviral treatment introduced in late 2004. METHODS: Patient case files, birth registers, death certificates, and mortality summaries were reviewed. Cause of death was assigned through clinical case discussion. Annual maternal mortality ratios were calculated and disaggregated by HIV status. RESULTS: During the 5-year period, 106 maternal deaths occurred out of 36,708 births (facility-based maternal mortality ratios 289/100,000 live births, 95% confidence interval [CI] 237–349/100,000). In 72% of cases, HIV status was known (76/106), with the majority being HIV-infected (78%, 59/76). Among HIV-infected women, only two had initiated antiretroviral treatment, and 70% of deaths were HIV-related (41/59), mainly from tuberculosis (21) and pneumonia (12). Direct obstetric causes of death such as hypertension and pregnancy-related sepsis predominated in women who were HIV-negative or of unknown status (48.9%, 23/47). Maternal mortality ratios in HIV-infected women were 776/100,000 (95% CI 591–1,000/100,000), 6.2-fold higher (95% CI 3.6–11.4) than in HIV-negative women (124/100,000, 95% CI 72–199/100,000). Changes in mortality over time were not detected. Although HIV testing increased 1.4-fold each year (95% CI 1.3–1.4) and estimated coverage of antiretroviral treatment for pregnant women reached 59.2% in 2007, levels remain suboptimal. CONCLUSION: In Johannesburg, HIV remains the major cause of maternal mortality despite integration of antiretroviral treatment into prenatal services. Maternal health services should target barriers to uptake of HIV treatment and care. LEVEL OF EVIDENCE: III

Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis.

Background:In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. Methods:HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented. Results:Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%. Conclusion:The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

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.

Staphylococcus aureus bacteraemia at two academic hospitals in Johannesburg

OBJECTIVES AND METHODS Staphylococcus aureus bacteraemia (SAB) remains a major problem worldwide. A retrospective study of patients with SAB seen from November 1999 to October 2002 was conducted at two academic hospitals in Johannesburg to determine mortality rates (death within 14 days of submission of blood culture) in patients bacteraemic with methicillin-sensitive (MSSA) and resistant S. aureus (MRSA) and to identify risk factors associated with mortality. RESULTS Of 449 patients with SAB, 104 (23.2%) died within 14 days of clinically suspected SAB. Of the 204 patients who acquired SAB in hospital, 6 patients died within 2 days, 39 between 2 and 14 days, and 41 more than 14 days after onset of SAB. One hundred and five patients (23.4%) had MRSA bacteraemia, 21 (20%) originating from the community. The MRSA bacteraemia rate among patients with hospital-acquired infection was 41.1%, significantly higher (p < 0.0001) than the 10.3% community-acquired MRSA bacteraemia. Thirty-five (33.3%) of the 105 patients with MRSA bacteraemia died within 14 days, compared with 69 (20.1%) of 344 MSSA patients (p = 0.0048). Admission to the intensive care unit (ICU) was significantly associated with mortality (p < 0.001)--30 of 79 patients admitted to ICU died (38%). Among 222 patients whose HIV status was known, 117 (52.7%) were positive, and of these 32 died (27.4%), a rate not significantly higher than that among HIV-seronegative patients (18 of 105 patients, p = 0.69). CONCLUSIONS Compared with MSSA, MRSA was shown to be significantly associated with mortality. Stay in ICU and infection with strains resistant to oxacillin, ofloxacin and rifampicin were highly significant predictors for mortality.

The detection of urethritis pathogens among patients with the male urethritis syndrome, genital ulcer syndrome and HIV voluntary counselling and testing clients: should South Africa’s syndromic management approach be revised?

Objectives: To determine the prevalence of urethritis pathogens amongst male symptomatic urethritis (MUS) patients, genital ulcer (GUS) patients without urethritis symptoms and men requesting HIV testing at a voluntary counselling and testing (VCT) clinic. Methods: A prospective study was conducted in Johannesburg, South Africa. Men from the three groups were screened for urethritis pathogens using molecular tests. Culture for Neisseria gonorrhoeae and, initially, trichomoniasis was performed. Antimicrobial susceptibility testing was undertaken for ciprofloxacin on all gonococcal isolates; ciprofloxacin resistant isolates were screened for ceftriaxone resistance. Results: 664 participants were recruited (438 MUS, 76 GUS and 158 VCT) over 2 years. Gonorrhoea was detected in 62.3% MUS, 15.8% GUS and 3.2% VCT participants. Chlamydial infection was detected in 19.3% MUS, 13.2% GUS and 8.2% VCT participants. Trichomoniasis was detected in 4.9% MUS, 19.7% GUS and 3.8% VCT participants. Mycoplasma genitalium infection was detected in 14.4% MUS, 13.2% GUS and 7.0% VCT participants. Ciprofloxacin resistance increased from 13.0% in the first year to 26.3% in the second year; all resistant isolates were susceptible to ceftriaxone. Conclusions: Urethritis pathogens, including Trichomonas vaginalis, should be covered in syndromic management treatment of genital ulcers in the absence of clinical urethritis. Consideration should be given to adding metronidazole to existing MUS treatment. Ciprofloxacin can no longer be relied upon to treat presumptive gonococcal infections in South Africa.

Why State policies that undermine HIV lay counsellors constitute retrogressive measures that violate the right of access to health care for pregnant women and infants

Abstract The authors make two distinct, but related, arguments. First, their empirical studies – conducted in three antenatal clinics in inner-city Johannesburg – demonstrate a strong correlation between (1) the government’s failure to provide adequate remuneration to and secure employment of lay counsellors for the provision of HIV counseling and treatment; and (2) the failure of many women and children to receive timely medical interventions. The data show that late payment of HIV lay counsellors has a devastating impact on HIV testing in these three clinics. The evidence also demonstrates that such timely HIV prevention and treatment is required for the survival of pregnant women and their neonates. Lay counsellors – through no fault of their own – are often unable to make these timely interventions. Second, the authors contend that the government–s conscious deployment of inadequately remunerated and institutionally marginalized lay counsellors instead of health care professionals (who had previously undertaken counselling and testing) constitutes a retrogressive measure in terms of s 27 of the Constitution. In short, despite the government–s commitment to an expanded, more efficacious ART rollout, it is currently delivering less health care – not more – and less access to adequate health care – not more or better – to this cohort of patients with HIV. Such retrogressive measures offend the Court’s own understanding of the delivery of this constitutionally-mandated public good to pregnant women with HIV and their infants. The failure of the government to provide adequate and timely remuneration and secure employment to lay counsellors rises to the level required for finding an unjustifiable limitation of s 27’s right of access to health care services. As the authors show, the violation flows from the improperly remunerated, insufficiently trained and generally marginalized manner in which lay counsellors are (mis)managed by a public health system that has chosen to supplant well-trained professionals with well-intentioned non-professionals in the delivery of essential components of now constitutionally-mandated ART and PMTCT programmes.

I get hungry all the time: experiences of poverty and pregnancy in an urban healthcare setting in South Africa.

BackgroundFor pregnancy to result in a healthy mother and infant, women require adequate nutrition and to be able to access antenatal care, both of which require finances. While most women working in the formal sector in South Africa obtain some form of maternity leave, unemployed women receive no such support. Additional interventions in the form of expanded social assistance to vulnerable pregnant women are needed. To help inform such an approach, we undertook a series of qualitative interviews with low-income pregnant women in Johannesburg.MethodsQualitative, in-depth interviews were held with 22 pregnant women at a public sector antenatal clinic in Johannesburg in 2011 to gather data on their greatest needs and priorities during pregnancy, their access to financial resources to meet these needs, and the overall experience of poverty while pregnant.ResultsA total of 22 women were interviewed, 5 of whom were primagravid. One woman was in the first trimester of pregnancy, while nine were almost full-term. All but one of the pregnancies were unplanned. Most participants (15/22) were unemployed, two were employed and on paid maternity leave, and the remaining five doing casual, part-time work. In most cases, pregnancy reduced participants’ earning potential and heightened reliance on their partners. Women not living with the father of their children generally received erratic financial support from them. The highest monthly expenses mentioned were food, accommodation and transport costs, and shortfalls in all three were reportedly common. Some participants described insufficient food in the household, and expressed concern about whether they were meeting the additional dietary requirements of pregnancy. Preparing for the arrival of a new baby was also a considerable source of anxiety, and was prioritized even above meeting women’s own basic needs.ConclusionsThough pregnancy is a normal life occurrence, it has the potential to further marginalise women and children living in already vulnerable households. Extending the Child Support Grant to include the period of pregnancy would not only serve to acknowledge and address the particular challenges faced by poor women, but also go some way to securing the health of newborn children and future generations.